Shigelosis
Shigelosis
Shigelosis
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ABSTRACT
Background: Shigellosis is an enteric disease caused by Shigella spp. and it is archetypically related to wander to high-risk
districts. It is an invasive disease of the colon caused mainly by Shigella sonnei and Shigella flexneri. The mode of
transmission is principally fecal-oral with low infectious dose as minimum as ten bacterial cells. Not surprisingly, Musca
domestica can act as a vector of transmission at the dirty region of inadequate human feces disposal. Invasion of the epithelial
cells covering rectum, the terminal ileum, and colon mainly depending on Shigella type three secretion system (T3SS),
leading to hemorrhagic diarrhea. Inflammatory and anti-inflammatory responses may occur a few hours after the invasion.
Methodology: Clinical manifestation includes fever and stomach cramps and rectal spasms (tenesmus) after exposing to
the bacteria after at least 12 h of exposure. Bloody diarrhea (as maximum as 50% of cases) usually contains mucus. Stool
culture on selective media such as Salmonella-Shigella agar (SS agar), xylose lysine dextrose (XLD) agar, Hekteon enteric
agar, and deoxycholate agar may help in the diagnosis of Shigella spp. Pale colony without blackness can reveal Shigella
spp. on XLD and SS agar. Serotyping is very important to confirm the diagnosis. Results: The prominent clinical symptoms
are bloody diarrhea accompanied in sometimes with mucus which may be resolved within 1 week of exposure. The post-
shigellosis consequence may include peritonitis, kidney damage, and hemolytic-uremic syndrome. The main virulence
factors responsible for clinical symptoms include enterotoxins: set1A, set1B, ShET1, and ShET2 carried on pathogenicity
islands. In addition to invasins, T3SS and immune modulation effectors proteins such as OspC3, OspF, OspG, OpsI OpsZ,
IpaH9.8, and IpaH0722 were implicated as virulence factors associated with clinical symptoms. Multidrug resistance isolates
were reported among Shigella spp., especially for third generation cephalosporins, fluoroquinolones, sulfonamides, and most
recently azithromycin. The present study concludes that Shigella spp. are amazing enteric pathogen with dual mode of
pathogenesis (both invasiveness and toxigenesis) and have very low infectious dose. They have arrays of virulence factors
that enable them from escaping and downregulation of the immune system. In addition, they possess effectors protein acting
as invasins and enterotoxins. The resistance to the empiric therapeutic options may push an alarm to seek about new choices.
*Corresponding author: Dr. Hussein O. M. Al-Dahmoshi, Department of Biology, College of Science, University of Babylon,
Iraq. E-mail: [email protected]
The endemic disease is caused, mainly by S. sonnei and cases. Although shigellosis is associated with a few
S. flexneri. Shigella colonizes and invades the colon, medical complications only, adequate control of this
preferentially aiming the colonic crypt.[5] Shigella is disease may decrease the overall diarrhea burden in
related to the acute inflammations. The essential steps the world.[12] It has isolated from different sources,
of the colonic infections by the bacterium Shigella namely, the aquatic body (such as rivers, the coastal
are including the adhesion, invasion, intracellular water, and the surface water), wild animals, birds,
replication, and cell-to-cell spreading. Each step is insects, and free-living amoebae. For a continuous
probably enough to be organized using eco-cues, transmission in humans, however, the bacterium must
involving the tension of oxygen, temperatures, the be passed from one person to another, as it does not
concentration of salts, and pH. Invasion of the host survive in the planktonic phase for long outside the
colonic epithelia by Shigella is depending on T3SA body.[13,14]
(type three secretion apparatus). Shigella incites the
controlled inflammatory responses, which involves SHIGELLOSIS TRANSMISSION
releasing inflammatory cytokines (IL1b, IL-8, IL6,
TNFb, and TNFa) and anti-inflammatory cytokines The principal approach of transmission is by feco-oral
(TGF-b and IL-10). During a few hours of invasion mode and as low as 10–100 FCU can cause an infection.
of Shigella in the mucosa of the colony, the useful Such low infective doses enable Shigella for causing the
influxes of inflammatory cells are seen, essentially large outbreak. The high incidences of Shigella in the
driven using the released IL-8 by the infected epithelial developing countries are mainly imputed to the absence
cell. Neutrophils and monocytes are detected, which of immaculate water, poor cleanness, malnutrition, and
characterize the prevalent population of the recruited contact of the close persons. The outbreak has been
cells. Lymphoid cell (essentially T cell) it may also related to person-to-person transmission in crowded or
clarify within the mucosa of the rectum of an infected unhygienic environments such as asylums and prisons.
patient. The spreading Shigella within the mucosa of The eco-factors such as temperature and rainfall may
the colony needs active fraudulence of immunologic clarify to affect the transmission.[15] The expression of
responses. They have formerly been exhibited that the virulence gene is activated when the bacterium is
Shigella incites monocytes, macrophages, and B ranged from 30 to 37°C, in the medium of pH 7.433,
cells apoptosis and depresses the migration of T and mild osmotic stress. The infections of Shigella may
cells.[6-8] Through phagocytosis, the neutrophil is be occurred in the year, but peak prevalence in summer
considered the key role which plays the clearance months has been reported. In most communities, the
process in Shigella, intracellular killing and releasing incidence is highest in dry and hot weather, possibly
antimicrobial molecules extracellularly. Nevertheless, due to the water littleness in such conditions limits
the confidential survival of neutrophils and Shigella
measures of handwashing and other hygiene which
beyond interaction stays controversial. It may clarify
decreases person-to-person transferring the bacteria.
that Shigella incites necrosis of neutrophil in the T3SA-
From Bay of Bengal islands, shigellosis is reported to
dependent manner. In contrast, it may clarify that the
occur mainly during rainy seasons, while low numbers
neutrophil actively kills Shigella on phagocytosis.[9,10]
of cases are recorded in winters.[16]
The present review aims to highlight the important
aspects of shigellosis such as virulence factors and In settings where disposal of human feces is
antibiotics resistance. unsuitable, flies, especially the common housefly
(Musca domestica), may be used as a vector for
SHIGELLA SPECIES transferring shigellosis. However, Shigellae have
The genus of Shigella pertains to Enterobacteriaceae been found in reservoirs of birds in a zoological
family. It includes four species. They are, Shigella garden in Madagascar, and muscle tissues of carcasses
flexneri, S. dysenteriae, S. sonnei, and S. boydii, of several wild animals from wildlife species in
further categorized into various serotypes according to Canada.[17] Several aquatic bodies have been found to
biochemical tests and differences in the antigen of O. show presence of Shigellae, and thus, another potential
Therefore, Group A (S. dysenteriae) has 17 serotypes, source of infection may be aquatic food which may
Group B (Shigella flexneri) has 14 subserotypes, be played an important role in Shigella transmission
and classical serotypes, while Group C (S. sonnei) if such food is harvested from sewage-contaminated
has only one serotype, and Group D (S. boydii) has water. Shigella species have also been found to
20 serotypes.[11] S. dysenteriae is deemed the most grow symbiotically inside Acanthamoeba castellanii
virulent species, especially the serotype (Type 1) implicating amoebae which live freely that may serve
due to its capacity to fabricate STX (Shiga toxin), as a transport reservoir for Shigella in water. Such an
which considered a potent cytotoxin. S. boydii, environmental gene pool may contribute to horizontal
S. sonnei, and S. flexneri generically do not fabricate transfer of genes among strains and emergence of
Shiga toxin; thus, cause shigellosis is mild in these virulent strains leading to outbreaks.[18,19]
responsible for actin depolymerization; and IpaB of infections of Shigella. The main approach to
and IpaC, pore formation OpsE1/2, an adhesion disseminate resistance to multiple agents is the
and OpsD3 with enterotoxic activity.[29-31] Shigella horizontal transfer of plasmids carrying antibiotic
declined inflammatory responses by transferring resistance genes (R-plasmids).[43] Usually, the isolated
effectors for suppression of the MAPK and NFκB plasmid carries resistance toward chloramphenicol,
signaling paths and epigenetically arrange the ampicillin, trimethoprim, streptomycin, sulfonamides,
inhibition of pro-inflammatory cytokines like and tetracycline. Macrolide resistance genes are also
IL-8.[32] Furthermore, Shigella is able to down-regulate commonly plasmid-encoded. Antibiotic treatments
producing antimicrobial peptides, involving human are commended for the patient with severe diseases,
β-defensin hBD-3, and the chemokines like CCL20, dysentery, bloody diarrhea, or inhibitory conditions
inducting to defective dendritic cell recruitment. This of essential immunity. In this patient, empiric therapy
permits for the increased replications, active infection must be supplied, whereas the results of culture and
of contiguous cells, and obviation of immunologic sensitivity tests will complete. In moderate diseases,
response. Furthermore, IcsA (indicates to as VirG) the main indication for treatment is to inhibit
is a T3SS-independent outer membrane protein act spreading the bacteria. Antimicrobial sensitivity tests
as autotransporter and as adhesion. Modulation of of pathologic isolates are detected.
immune response by many Shigella proteins such as
OspC3, act to inhibit death of caspase-4-mediated The first drug used for treatment Shigella infection
inflammatory cells; OspF, inactivates MAPKs; was sulfonamides, followed by tetracycline and
and OspG, OpsI, OpsZ, IpaH9.8, and IpaH0722, chloramphenicol, respectively. The resistance of
inactivates NFκB.[33-36] Shigella developed to these antibiotics, thus turning the
treatment into ampicillin and cotrimoxazole. Moreover,
Enterotoxin 2 (ShET-2) and enterotoxin 1 (ShET-1) recommendations of the treatment were changed back
of Shigella are two critical factors proposed to to nalidixic acid because Shigella species advanced
mediate premature secretion of fluid of the jejunum to resistance to the previous drugs. After that, the resistance
demonstrate the infections in colons and to synthesize ability to nalidixic acid was developed, and shortly
property watery diarrhea showed premature in after the introduction of fluoroquinolones, while, now
Shigellosis. The common name is due to its similar today, the resistant strains for fluoroquinolone were
characteristics, such as enterotoxins, where there is no isolated from different sources. The WHO commends
similarity between ShET2 and ShET1.[37] using bifemesillinam, azithromycin, and ceftriaxone
to treat infections with species of resistant Shigella to
TREATMENT AND ANTIBIOTIC fluoroquinolones.[44] Antibiotic resistance is increasing
to common antibiotics among species of Shigella
RESISTANCE
globally. Furthermore, MDR for Shigella infections
Antibiotic treatments are always recommended in is widespread. In species of Shigella, the resistance
patients with severe or mild symptoms as it can decrease of trimethoprim, ampicillin, streptomycin, and
the severity and duration of symptoms, excreting streptothyricin is sometimes related to the finding of
microorganisms, and preventing complications 3. an integrated Class 2 and Class 1 containing resistant
Moreover, empiric antimicrobial therapy requires gene strips. Nevertheless, there is little data available
knowledge of the local antibiogram of circulating to characterize the prevalence of the first and second
Shigella strains. Especially, important is the awareness classes of species of Shigella.[45]
of the global emergence of multidrug-resistant (MDR)
Shigellae, notably the increasing resistance to the third CONCLUSION
generation of fluoroquinolones and cephalosporins
and most recently azithromycin.[38,39] Shigella spp. are amazing enteric pathogen with
dual mode of pathogenesis (both invasiveness and
Antibiotics have been shown to reduce the duration toxigenesis) and have very low infectious dose. They
of diarrhea and fever by approximately 2 days. In have arrays of virulence factors that enable them from
the loss of special antibiotic treatments, the patients escaping and downregulation of the immune system.
with gastroenteritis caused by Shigella may omit In addition, they possess effectors protein acting
the microorganism for up to 6 weeks in the absence as invasins and enterotoxins. The resistance to the
of the symptoms. The shorter duration of shedding empiric therapeutic options may push an alarm to seek
with antibiotic treatment can decrease the risks about new choices.
of person-to-person spread.[40-42] The increased
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