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Microsoft word - b 9 - pdfmachine from broadgun software, http://pdfmachine.com, a great pdf writer utility!id9409968 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com 88 / Health in Emergencies and Disasters Shigellosis in Disasters: its detection, treatment, and methods to
deal with it in disasters
Mohammad, Heiat1. Isa, Malmir2. Hossein, Aghamollaei3. Mohammad
Raza, Rezaeimehr4. Hamid, Kooshki5. Atefeh, Yaali Jahromi6
Introduction: Shigellosis, known as a bacillary diarrhea, is an infectious
disease that begets by a gram negative bacterium called shigella. Shigella,
as an invasive pathogen, has a powerful ability to cause diarrhea even with
a small number of bacteria. It is one of the most important and potentially
dangerous agents which can cause outbreaks in disasters. Investigation on
Shigella, its prevention, treatment, modes of detection and also hygienic
guidelines can reduce shigellosis related consequences in disasters.
Methods: This is a review study in which to find the required articles we
searched through related databases like PubMed and Elsevier. Following
keywords were used in this regard: bacteria species, growth conditions,
virulence factors, diagnosis, treatment of shigellosis. Obtained data were
categorized, analyzed and divided into different sections.
Results: Findings about bacterial morphology, growth properties, antigen
patterns, clinical symptoms and diagnosis of Shigellosis, treatment,
outbreak prevention in the crises and view points of some experts were
Conclusion: Public and strategic educations about this pathogenic agent
can decrease the backwash of epidemic events. Preparation of a plan to
draw social preparation against shigellosis is can be of effective strategies
to combat shigellosis in disasters.
Keywords: Shigellosis, Treatment, Detection, Disasters
1 - Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences 2 - Baqiyatallah University of Medical Sciences 3 - Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Corresponding author 4 - Jahrom University of Medical Sciences 5 - Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences 6 - Jahrom University of Medical Sciences Shigellosis in Disasters: its detection, treatment, and methods to deal. / 89 Introduction
Enterobacteriaceae account as a wide group of non-spore and Gram
negative bacteria which some of them normally live in the human intestine
. Numerous of bacteria include Escherichia coli, Salmonella, Klebsiella,
Proteus, Entrobacter and Shigella are the main members of this family.
Despite normal flora of human intestine is composed of some of this group
like E. coli, but the presence of some other members such as various strains
of Shigella can cause disease in human . For the first time, Shiga, a
Japanese scientist, could separate shigella from the environment. First
report of shigellosis, a disease caused by Shigella, referred to 4th century
AD. As shigellosis can rapidly contaminate a lot of soldiers and refugees, it
must significantly be mentioned from the viewpoints of disasters and
military [4 5]. At recent 100 past years, S. dysenteriae serotype 1 was
introduced as the essential cause of epidemic diarrhea with different
mortality rate through the world. . During 30 past years several wide
pandemics caused by S. dysenteriae serotype 1 has been reported in Central
America, Bangladesh, south and central Asia, Middle East and South
Africa. There is not still enough and exact information about the number of
patients all over the world . Nonetheless some estimations and also
conservative survey suggested that approximately 90 million of people
annually involve to diarrhea which more than 100 thousand of them will
die. Most of these mortality cases occur among children who live in
developing countries. According to the data reported by WHO, Shigella
causes severe disease in passengers and military personnel in the industrial
countries. On average, more than 18 thousand shigellosis cases are reported
annually in the United State. Children, elderly and weak people are the
most competent persons to catch this disease. Patients with immune
deficiency disease such as HIV positive persons are severely encountered
to disease  However according to statistical surveys, people who live in
developing countries have the more risk for catching disease and the
mortality rate in such country is more than industrial ones so that annually
about 5 to 15 percent of patients will die . Shigella is one of the most
important and potentially dangerous agents which cause disease outbreak in
disasters, so investigations about Shigella and its related issues like
prevention, treatment, and detection methods and also hygiene guidelines,
can reduce shigellosis damages in the disaster events. Therefore our main
goal in this review article is to illustrate some problems and collect some
categorized information about said points.
90 / Health in Emergencies and Disasters Methods:
In this review article we tried to extract data around the main concept
through the known databases include PubMed, Elsevier, Scopus and
EMBASE until 2013 to get relevant articles. During this process some of
the most important keywords such as Shigella, treatment, prevention,
pathogenicity, virulence mechanism, detection etc were used. Regardless to
any categorization, about 80 full articles and 40 Abstracts were found from
mentioned sources and subsequently different methods and information
were classified and compared with each other. Then the main collected
points were summarized, analyzed and divided into different sections. In
order to more analysis, obtained results about bacterial morphology and
growth properties, antigen patterns, clinical symptoms and diagnosis of
Shigellosis, treatment, outbreak prevention in the crisis condition etc, were
presented to some experts and their view points were embedded in article.
Finally, all income items and findings were grouped in different content.
Morphology, Growth properties and Stains of Shigella
Shigella is bacilli shaped, non-motile, non-spore and flagella and non-
capsulate bacteria. Short coco-bacilli shape of bacteria can be observed in
the fresh culture. It is 1-6 micrometer in length and 0.3-1 micrometer in
diameter [2 4]. While Shigella is an aerobic bacterium it can be alive in
anaerobic conditions. The antigen pattern of shigella is very extensive and
complicated. This bacterium has a lot of joint antigen with other genus of
enterobacteriaceae. shigella doesn’t have the H antigen. Its O-antigen is
made of lipopolysaccharide. The polysaccharide site of O-antigen is very
exclusive and makes it different from other types of antigens. [2, 4] Based
on O-antigen part of lipopolysaccharide, Shigella genus divided into four
groups include group A (S. dysenteriae), group B (S. flexneri) group C (S.
boydii) and group D (S. sonnei)[10, 11]
Various types of Shigella strains are more sensitive to physical and
chemical agents rather than salmonella or other enteric bacteria. Shigella
dysenteriae is more sensitive rather than other strains.
Shigellosis in Disasters: its detection, treatment, and methods to deal. / 91 Shigella sonnei is more resistant among others against cold and dryness.
Incubation for one hour at 55ºC and phenol 1% for 30 min can kill the
Shigella bacterium. Shigella cannot tolerate the high acidic concentrations.
Also high concentration of bile salt will block the growth rate. Shigella is
sensitive to light and dryness while low heat and humid conditions is
suitable for its growth so that it is able to be alive in water with normal
temperature for six months. Dried diarrhea reproductive bacilli on bed sheet
can be alive for six weeks. Shigella can be alive for about 10 days in soil. If
feces have the alkaline pH, bacteria will be able to be alive for some days
but in acidic pH those are rapidly killed. Pasteurization and colorization can
generally kill and remove Shigella contamination .
Bacterial pathogenesis factors
Before addressing the details of virulence factors, we refer to a series of
key points. Cellular pathogenesis and clinical manifestation of shigellosis is
the sum of a large number of bacterial virulence factors. The main part of
molecular mechanism of Shigella is invasion to the host cells and
intracellular survival. The factors which controls this part are coded on both
virulence plasmid and the chromosome [5, 12, 13] Some infectious islands
are in Shigella’s Chromosomes and plasmids named PAI. The islands are
usually between different Insertion sequences that can transfer genes from
plasmid to chromosome and vice versa, making various varieties [14, 15].
So-called SHI are the PAIs on chromosomes. They have some types like
SHI-1, SHI-2, SHI-3, SHI-O and SRL. Some of Pathogenic proteins factors
encoded by plasmid include: 1) virF (virulence F): The position of this
gene is almost 50 kb far from the plasmid replication initiation origin. This
gene encodes a 30kD protein that is responsible for invasion and is
necessary for regulating the expression of virulence genes. 2) virG: This
gene encodes a 130kDa protein placed in the outer membrane of bacteria.
This protein acts as a cell surface antigen that is responsible for
concentrating the F-actin and puts the actin filaments at the end of the
bacterium to form a long tail. 3) virB: virB gene is activated by the virF
gene production. virB gene produce a 33kD protein that regulates the
transcription of genes in the ipa operon [16, 17].
92 / Health in Emergencies and Disasters 4) icsA (Inter cellular spear): This gene encodes a 100kDa protein that
expands infection among cells. 5) icsB: encodes a protein that appears on
the bacterial surface and is required for cell to cell spreading. 6) ipaA, B, C,
D (invasion plasmid antigen): Productions of these genes are important
antigens and the host of Shigellosis will have a strong humoral immune
response against these antigens. These antigens are present on the cell
surface. They include: a) ipaA: encodes a 78kDa protein. Activity of this
protein is partly unknown, but its role in actin depolymerization in the host
cell recently has been established. b) ipaB: encodes a 62kDa protein that
after inducing by IpaD is called to be recruited on the cell surface and after
making a complex with IpaC creates a pore in the host cell membrane. c)
ipaC: encodes a 43kDa protein that together with IpaB and IpaA form
acomplex interacting with the host cell membrane and stimulate cellular
signal cascades to the entry of bacteria through endosom. d) ipaD: encodes
a 37kDa protein applying IpaB on the bacterial surface and begins invasion
Lipopolysaccharide is suggested as an antigen of Shigella and is considered
as a component of bacterial virulence factors. Lipopolysaccharide is a
complex combination of lipids and polysaccharides. Its molecular weight is
about 10kDa and is usually hydrophobic and its toxicity is due to lipid A
[19, 20]. Shiga toxin composed of A and B subunit, which is as a set of
hexamer with molecular weight of about 70kDa.
Populations that are at risk of shigellosis
All people could be susceptible to this disease. However, children in
kindergarten centers, native Caucasus, international travelers, gay men, and
patients with HIV infection are at highest risk of disease [4, 21].
Populations of insects such as mosquitoes and flies are abundant in regions
that are as well as a group of people who are living in camps or are at risk
does, because the disease can be transmitted from person to person and the
most transfer mediums are food, fingers, feces and flies. Swimming in
contaminated water with this bacteria, using equipments suspected to be
Infected specially items associated with food can increase the risk of
catching the disease.
Shigellosis in Disasters: its detection, treatment, and methods to deal. / 93 Clinical symptoms of Shigellosis
Disease caused by Shigella is called Shigellosis. Shigellosis is an infectious
disease that affects a part of the small intestine. Most Symptoms of Shigella
infection include diarrhea, fever, nausea, vomiting, cramps and abdominal
pain, blood, mucus or pus in the stool. Sudden onset of shigella is
associated with abdominal pain, fever and watery diarrhea that just occurs 4
hours after bacterial spreading in the ileum and colon.
Daily, 300-200 mg serum protein is also lost in the feces. Its symptoms will
be observed between 1 to7 days after entry of bacteria. The diagnosis is
based on blood and feces. Neutrophil in stool smear is a reliable sign of
infection. . Bacteria produce toxins that usually attack the epithelial cells
of the colon and causes wounds and inflammation in the intestinal wall.
These toxins may have two roles, firstly, the toxin acts like enterotoxin and
produce watery diarrhea, which occurs early in the disease, secondly, after
local invasion of bacteria in the gut due to inhibition of protein synthesis
and cytotoxic properties, the cells are destroyed and the wound is created.
In this situation, diarrhea with blood and mucus is observed. Toxin binds to
receptors on the surface of epithelial cells and activates adenylate-cyclase,
so that water and electrolytes flow into the intestine. Endotoxin has clinical
effects such as hemorrhage, falling blood pressure, leukopenia, and
hypoglycemia. Adrenal gland is vulnerable to the toxin [4, 21].During
diarrhea, Shigella can be found in stool with approximate rate of 106-108 [4,
21]. After bacterial colonization in the intestine the number of bacteria
increases to ten billion bacteria per cubic centimeter in stool.
Laboratory Diagnosis of Shigellosis
Samples are excreted feces, mucus and blood. The best samples for
diagnosis achieves in rectum sigmoid by using of a swab. Stool samples
could also be used for laboratory diagnosis. For this purpose direct method
of stool examination, stool culture and serological tests are used. These
bacteria have the ability to shift to Viable But Non-Culturable (VBNC)
phase and thus can hide itself from the perspective of conventional
diagnostic systems . Laboratory Diagnosis of Shigellosis includes:
94 / Health in Emergencies and Disasters 1) Direct stool examination: The direct stool examination cannot
distinguish between diarrhea producing bacteria from each other. Infection
source can be detected via identical methods include a cytology method of
stool and the presence or absence of ameba or other parasites. In the
hemorrhagic bacillary dysentery, approximately 90% of cells existed in
stool consist of polymorph nuclear cells while in the amebial diarrhea and
salmonella diarrhea there is lower rate of PMNs and more monocytes. 2)
Stool culture: In the primary stage of the disease we can isolate the diarrhea
producing bacteria from stool culture. Stool culture must be performed
immediately after defecation because shigella will die due to the effects of
stool’s coliforms and its lower pH.
If immediate culture is not available the stool sample must be preserved in
the glycerol buffer up to prepare instruments. Different kind of media such
as deoxicolat citrate, salmonella Shigella, Mc conky etc can be use For
culture [4, 21]. 3) Serological examination: The healthy serum can contain
antibodies against Shigella. Therefore in the cases that increasing of
Antibody titer among two tests performed in 10-15 days interval is
important. Recently the indirect hemagglutination methods in which LPS
connects to RBC membrane has been suggested.
Shigellosis prevention and Treatment
Shigella transmitted between humans by foods, feces and contaminated
instruments. Most of Shigella infections were seen in the children at the age
of less than 10 years old. In the militaries the use of drugs for shigellosis
prevention was performed in the restricted times. Unfortunately, due to the
wrong chemoprophylaxis, the drug resistant mutants were rapidly revealed.
Since the human is a major host of pathogenic Shigella, for this reason the
prevention methods for this organism from its sources must be associated
with these parameters. 1) Sanitary control of water, foods, dairy products,
from its and wastes. 2) Isolation of patients. 3) Identification of carriers
special persons that work with foods [23, 25]. Nowadays, effective
vaccines against Thyphoidal fever and Vibrio cholera are available but
there are not available a suitable vaccines against pathogenic agent such as
Campylobacter, human calsiviridae, entrotoxigenic E. coli and Shigella.
Since several years ago many studies about producing an efficient vaccine
that acts as an anti-shigellosis were performed. Some oral attenuated
vaccines such as bivalent Shigella flexeneri type 2a and bivalent Shigella
sonnei were made. The successful function rate of these vaccines was
approximately 61%-65% for bivalent Shigella flexeneri type 2a vaccine and
57%-72% for bivalent Shigella sonnei vaccine. Other Types of these
Shigellosis in Disasters: its detection, treatment, and methods to deal. / 95 vaccines such as a live attenuated Shigella flexeneri type 2a (SC602) and
Shigella dysenteriae type1 (SC599) were also prepared which had a
mutation in toxA (stx), int, iuc, icsa (virG). Final evaluation of these
vaccines did not show a good results in human . In the other hand
recombinant vaccines were also developed. In 2000 Turbifil and his
coworkers isolated and characterized the subunits of invasion protein
complex (IpA, B, C). Then they analyzed their immunogenicity effects in
the mouse and guinea pig. results showed the evaluated antibody titer
against LPS and Ipa . In 2006 a vaccine composed of IpaB, IpaC,
IpaD that called invaplex passed the animal tests and showed a good results
in the challenge with Shigella . The latest investigation to produce a
vaccine against Shigella refers to year 2008. When researchers established
an invention that showed the IpaD polypeptide and its functional
derivatives can produce anti-IpaD which is severely able to prevent
shigella invasion . Shigellosis treatment principally associated with oral
rehydration solutions contain enough salt (sodium) to increase the level of
ions decreased due to diarrhea. Oral rehydration for many of the patient
was satisfied. Furthermore it may that some of the patients need
intravenous rehydration. In many cases, the disease can be healed after 4 to
8 days without the use of any antibiotics. For shigellosis treatment, in the
cases of patients that are very young or very old use of antibiotics such as
ampicillin, ciproploxacilin, nalidixic acid and trimethoprim are suggested.
When disease is in a very acute form and the risk of morbidity is high, in
addition of the last antibiotics the use of ampicillin not amoxicillin is
necessary. For shigellosis treatment anti-diarrhea drugs such as
diphenoxilate and lupramid cannot be used, because they increase the
period of infection. Researcher reports reveal that the use of 1 unit (2.5 gr)
tetracycline orally can be useful for acute cases of dysentery. At present,
ampicillin is a selective drug for shigellosis treatment that must be
consumed 2 gr per day for 5 days in adults. For children this drug must be
consumed 100mg per 1 kg of body weight. Cotrimoxasole can be used as
an appropriate alternative for ampicillin [7, 23, 24].
Outbreak prevention in the crisis condition
According to the top passages the importance of identification, prevention
and treatment of Shigella completely advise. For these reason to prevention
of shigellosis outbreaks in the crisis condition follow points must be
considered. 1) Education: People must be known the primary knowledge
about shigellosis. They must be known shigellosis symptoms, transmission
ways, outbreak prevention and control disease .they must help each other to
96 / Health in Emergencies and Disasters understand those risks. In other words the knowledge is the best way for prevention of shigellosis outbreak. People that have enough knowledge about disease live in lower risk. 2) Consumption of Packed Food: Although using the pattern of water consumption and packed and hygienic food does not seem economic, it can be a perfect economic measurement in preventing infectious agents such as shigela which can be transmitted through infecting food. In such situation preparation and prediction of packed food is a significant measure for urgent use. However in any situation it is recommended not to use unsafe specially open and unpacked food. 3) Vaccination: Vaccination of exposed groups in the areas which has a high possibility of creating unexpected adventure can restrain shigella’s outbreak. If vaccination is impossible, preparation and prediction of necessary vaccine & anti-serums can keep exposed people safe in urgent situation.4) Preparation of Individual equipment: Equipments such as water Filtration instrument and chlorine tabs can be useful to be ensured of water safety. Aid teams must be equipped of special dressing, disinfecting agents, and sampling devices. 5) Preparing disinfecting agents: Predicting the preparation of disinfecting agents in order to disinfect major sources of infection like water tanks in a wide volume can be a measure toward to decreasing the risks and number of patients due to shigellosis. 6) Drugs’ preparing: Predicting and preparation of necessary drugs is a vital measurement for the treatment of people and patients. The suitable amount of stock and the area of drug stores must be pre-determined. These predictions can lead to performance of useful and quick measurements in order to access the drugs.7) Environment Improvement: Development and expansion of urban and rural environment in order to prevent food and water pollution and hygienic burial of rubbish can lead to the decrease of people infection to diarrhea. 8) Empowering and Promoting Safety Points: Empowering and promoting safety points within a country which follows personal & social safety promotion will be a big step in conflict to probable application of biologic agents. Using bio-safety rules in all hygienic clinical centers and preventing illegal people traffic into lab. Centers & hospitals can increase safety coefficient. 9) Empowering Hygienic Remedial Systems: In order to diagnose, prevent, and remedy, the hygienic remedial system must be empowered. If the hygienic remedial system of a country is more powerful and advanced, preventing, diagnosing, and treatment of infecting agents such as shigela will be performed in less time and low cost. Below is the list of vital measurements which are important factors to empower the hygienic remedial system. 10) Making labs equipped: Prediction and making country’s labs equipped toward quick, accurate, and Shigellosis in Disasters: its detection, treatment, and methods to deal. / 97 proper diagnosis of the infectious agent can announce the danger at least possible time. Performing the test of periodic sensitivity of the infectious agent’s antibiotic resistance in the labs and reporting their results to responsible centers is a kind of readiness toward conflict to the disease. The preventive measurements can be performed through labs’ caution and prevent the danger of society health via daily tests of drinking water, food, sampling, and hygienic control of the environment regarding the existence of pathogen’s microorganisms before spreading the infectious agent. Nowadays the significance of using quick diagnosis methods of biologic factors and their toxin such as PCR and ELISA and LFA systems is completely cleared for all hygienic remedial systems of the world countries and also follows gallant advances. Many bacterial and fungal agents and toxins which are transmittable through food can be diagnosed via these methods. Researchers with the aim of accessing to technical knowledge of producing quick diagnosis kits numerously must be performed by researchers and research centers. 11) Prediction of quarantine and isolation: Necessary prediction for patients’ isolation and even quarantine of injured and the patients with shigella diarrhea far from normal ones will be urgent and prevent spreading infection. 12) Epidemiology Studies: Epidemiologic survey in different areas toward disease assessment and creating applicable systems in order to report cases to clinics immediately is a kind of preventive measurement toward infection control in a crisis. 13) Informing: The country’s hygienic remedial system including state and private sectors, welfare, etc. must have the ability of encountering possible adventures and infection outbreak via systematic contact. Informative system requires cooperation of coherent organs such as the organizations related to public hygiene, medical researches’ centers, administrative of hygienic services and their network, occupation groups, medical & hygienic equipment makers, broadcasting, press, and international organizations. Connecting infectious sectors with each other and receiving momentarily reports and accurate executing of rules and hygienic standards under the survey of infection experts in conflict to any possible adventure will depend on suitable organizing of medical team. While an unexpected adventure happening, giving proper & enough information at a suitable time to people is necessary to prevent any toll and decrease their panic and fray. It is obvious that the decreasing mortality amount, preventing adventure occurrence, and decreasing crude reaction of people against these adventures are some of the aims of this program. 98 / Health in Emergencies and Disasters Conclusion:
Shigella is an important productive factor of inflammatory acute diarrhea
and a gram negative bacterium without Spore which can create disease with
a low amount. Disregarding hygienic principles, polluted water and food
sources, which will be created in a crisis easily, are the major factors of
spreading this bacterium and infection accordingly. Training exposed
people before the adventure occurrence is the most important principle of
encountering to infection. As shigella is one of the most dangerous and
spreading factors of making disease in most unexpected adventures.
Making people informed of this factor and its derived diseases can be a
preventive measurement toward decreasing the number of affected ones.
However adjusting a compiled program for continuous training of people of
the society is a prompt affair. Subjects like using packed food, prediction
and preparation of disinfecting agents, observing personal hygiene,
preparing individual equipment and the guidance of their usage, preventing
the spread of infection to the others, required drugs and the way of their use
are such cases which must be notified in training. Local and country
authorities must also be trained and these training should be repeated and
updated on a regular program. Performing maneuver can determine
strength and weakness points. Developing hygienic remedial system is the
most duty of authorities. In order to decrease the amount of toll and cost in
crisis situation, improving the environment and water nets, drug prediction
in sufficient amount and determining a suitable place for their storage,
adjusting bio-safety principles, and making them local must also be
performed before the crisis. Developing quick systems for Shigella
diagnosis, based on molecular methods and making lab and clinical centers
equipped of these diagnosis system is necessary for timely reaction to
Shigella outbreaks. Moreover, creating networks in order to immediate
report of suspect and confirmed cases to the related authorities is necessary
to decrease epidemic situations.
Shigellosis in Disasters: its detection, treatment, and methods to deal. / 99 References:
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Poux – Pédiculose CONSEIL SUPÉRIEUR D'HYGIÈNE PUBLIQUE DE FRANCE SECTION DES MALADIES TRANSMISSIBLES Séance du 17 janvier 2003 Conduite à tenir devant un sujet atteint de pédiculose du cuir cheveluLe groupe d'experts était composé de :Dr. I.Bidault (Agence française de sécurité sanitaire des produits de santé )Dr. C.Bodemer (hôpital Necker, Paris)S.Casanova (direction