UNIVERSITY OF GONDAR

COLLEGE OF MEDICINE AND HEALTH SCIENCES

SCHOOL OF BIOMEDICAL AND LABORATORY SCIENCES

DEPARTMENT OF MEDICAL MICROBIOLOGY

Global Burden of Salmonellosis and Shigellosis in diarrheic Pediatric

Population

By: - Amare Alemu (Bsc)

Advisors: - Setegn Eshetie (Bsc, Msc)
Tigist Engida (BSc, MSc)

December, 2017
Gondar, Ethiopia
ACKNOWLEDGEMENT
I would like to thank SetegnEshetie and TigistEngida to let me come up with this valuable
seminar topic and offering for their tremendous technical support. I would like to extend my
gratitude to School of Biomedical and Laboratory Sciences and Department of Medical
Microbiology for their technical support and enrolling me as MSc student.

I
Contents
ACKNOWLEDGEMENT .............................................................................................................................. I
Abbreviations ......................................................................................................................................... III
Summary ................................................................................................................................................ IV
1. Introduction ........................................................................................................................................ 1
1.1. Background................................................................................................................................... 1
2. Literature review ................................................................................................................................. 3
2.1. General Characteristics of Salmonella and shigella species............................................................ 3
2.2. Classification and nomenclature ................................................................................................... 4
2.3. Epidemiology ................................................................................................................................ 4
2.4. Transmission ................................................................................................................................. 7
2.5. Pathogenesis .............................................................................................................................. 78
2.6. Virulence factors ........................................................................................................................... 9
2.7. Clinical manifestations ................................................................................................................ 10
2.8. Diagnosis .................................................................................................................................... 11
2.9. Treatment, prevention and control ......................................................................................... 1112
3. Significance of the review .............................................................................................................. 1213
4. Methods ........................................................................................................................................ 1213
4.1. Search strategies..................................................................................................................... 1213
4.2. Study selection ........................................................................................................................... 13
5. Conclusion ..................................................................................................................................... 1314
6. Reference ...................................................................................................................................... 1415

II
Abbreviations
AIDS--------------------------------------Acquired Immuno Deficiency Syndrome
CDC---------------------------------------Centers of Disease Control
EIEC--------------------------------------EnteroinvasiveEscherichia coli
GALT------------------------------------- Gastrointestinal Associated Lymphoid Tissue
HCL----------------------------------------Hydrochloric Acid
HIV-----------------------------------------Human Immuno Virus
IpaB--------------------------------------- Invasion of plasmid antigen B
LPS-----------------------------------------Lipopolysaccharide
MLST---------------------------------------Multiple Loci Sequencing typing
NTS----------------------------------------- Non-Typhoidal Salmonella
PFGE -------------------------------------- Pulse-field Gel Electrophoresis
PMNs---------------------------------------Polymorphonuclear cells
RES----------------------------------------Reticuloendothelial System
T3SS---------------------------------------Type III-Secretion-System
WHO---------------------------------------World Health Organization
USA----------------------------------------United States of America

III
 Commented [D1]: Not looks like a summary, please consider
Summary the following formats
Background: - Salmonella and Shigella are members of the Enterobacteriaceae characterized by Background:
Aim of the review
non-lactose fermenters, gram-negative rods, non-spore formers and facultative anaerobes. The Methods
Literature review
Conclusion
Shigella species are non-motile, and non-gas producers. and Salmonella species are motile, Keywords:
produces acid and gas from glucose, normally inhabit the intestines of animals and humans. Formatted: Font: Bold, Not Italic

Aim of the review:- Members of the genus Salmonella are ubiquitous pathogens found in Formatted: Font: Bold
Formatted: Font: Not Italic
humans and livestock, wild animals, reptiles, birds, insects.The genus Shigella encompasses four
Formatted: Font: Not Italic
subgroups historically treated as species. Shigella species are found only in the human intestinal Formatted: Font: Not Italic

tract. Formatted: Font: Not Bold

Primarily Salmonella and Shigella transmitted through ingestion of contaminated food and water.
Children living in areas with poor sanitation are at higher risk for fecal-oral transmission. Food
and water contamination will result in a higher risk of acquiring infection caused by Salmonella
and Shigella.
When the bacteria enter the digestive tract via contaminated water or food, they tend to penetrate
the epithelial cells lining the intestinal wall. SPIs encode for type III secretion systems, multi-
channel proteins that allow Salmonella to inject its effectors across the intestinal epithelial cell
membrane into the cytoplasm.
Strains of Shigella spp. are non-motile and it is not known how the bacteria reach and adhere to
M cells.The capacity of the bacteria to cross the colonic mucosa via M cells associated with
Gastrointestinal Associated Lymphoid Tissue (GALT) and reprogram epithelial cells to produce
pro-inflammatory mediators, such as interleukin 8, which play a major role in the strong
inflammatory response facilitating further bacterial invasion. This triggers an intense acute
inflammatory reaction with infiltration by polymorph nuclear leukocytes. The shigella species
cause bacillary dysentery leading to watery or bloody diarrhea.
Shigella virulence is based on the presence of a large virulence invplasmid, carrying an operon
that encodes the type III-secretion-system (T3SS) responsible for bacterial entry. The T3SS is
composed of several proteins which connects the inner and outer bacterial membranes. Commented [D2]: This story indicates background information,
so please make it concise and short not more than one small
paragraph.
Formatted: Space After: 0 pt, Line spacing: 1.5 lines

IV
 1. Introduction
1.1. Background
Human diarrheal diseases have been recognized from the beginning of civilization and remain one of
the most prevalent public health problems of today. Gastrointestinal infections due to pathogenic
Enterobacteriaceae in particular Shigella and Salmonella species are significant causes of morbidity
and mortality worldwide; mainly children under the age of 5 years are at high risk (1, 2). Recently,
the World Health Organization (WHO) estimated that 1.1 million deaths per year are attributed to
shigellosis (3).

Salmonella and Shigella are members of the Enterobacteriaceae characterized by non-lactose

fermenters, gram-negative rods, non-spore formers and facultative anaerobes (4). The Shigella
species are non-motile, and non-gas producers’(4, 5) andSalmonella species are motile, produces
acid and gas from glucose, normally inhabit the intestines of animals and humans(4, 6).

The pathogenesis of Salmonella species is characterized by the invasion of non-phagocytic

cells.Salmonella will penetrate into the intestinal epithelial cells by inducing their own uptake, in a
complex and active process that morphologically resembles phagocytosis(4, 5).They invade the
mucosa of the small and large intestines and produce inflammation. Invasion of intestinal epithelial
cells induces an inflammatory reaction which causes diarrhea due to Salmonella infections(4, 7).
The virulence factors associated with Salmonella species such as adhesion, invasion, and toxin genes
are clustered in certain areas of the chromosome known as “Salmonella pathogenicity islands (4, 8) Commented [D3]: Merge these two paragraphs

Most of the current knowledge on mechanisms of Shigella pathogenesis is derived from studies of S.
flexneri.The Shigella species enters and invade the intestinal mucosa by using M cells of the
intestinal epithelial cells as the portal of entry(8). The bacteria are highly infectious, since as few as
10 to 100 microorganisms are sufficient to cause disease(8-10). Because of delay in humoral
responses, complication and mortality rate due to shigellosis in children is higher than in other age
groups (5, 9). The highest susceptibility of this age group may be due to the fact that children less
than 2 months old produce little hydrochloric acid (gastric HCl), a natural barrier to many
microorganisms (4, 7).The severe tissue destruction caused by Shigella species results in an impaired
adsorption of water, nutrients, and solutes, which might cause the watery diarrhea as well as the
blood and mucus in stools characteristic of shigellosis A disturbance of electrolyte homeostasis and

1
changes in membrane transport processes, such as uncontrolled ion and fluid secretion, are typical
ofdiarrheal disease. Shigella enterotoxins which are produced by several Shigella strains, were found
to induce fluid secretion into the intestine, thus accounting for the watery phase of diarrhea (8).

The virulence plasmid is an essential virulence determinant of all Shigella species and encodes the
molecular machinery necessary for tissue invasion and the intracellular lifestyle. The Shigella species
have a lot of virulence factors that allow it to adhere to the epithelium of the intestine, survive
stomach acid, invade host cells, evade immune responses, and introduce toxins into the body.
Invasion of plasmid antigen B (IpaB) initiates binding to the host cell and initiating pathways that kill
macrophages upon infection, IpaC activates proteins to form the actin-polymerizing complex that
allows Shigella to move and spread within host cells (4, 10).Shigella virulence is based on the
presence of a large virulence invplasmid, carrying an operon that encodes the type III-secretion-
system (T3SS) responsible for bacterial entry (11).

The Salmonella and Shigella are transmitted from person to person usually by asymptomatic carriers
and via contaminated food, flies, feces, fingers, and water (4, 5, 11, 12). A severe infection of
diarrhea in children is highly associated with risk factors such as poor environmental sanitation and
hygiene, poverty and malnutrition (11, 13).

Salmonellosis and shigellosis can be diagnosed by using culture and molecular techniques (4).
Prevention and control of salmonella rely on the strategies that prevent spread of the organism within
the community and from person to person. These include: hand-washing with soap, ensuring the
availability of safe drinking water, safely disposing of human waste, breastfeeding of infants and
young children, safe handling and processing of food, and control of flies and health education (5).

2

2. Literature review
2.1. General Characteristics of Salmonella and shigella species
Salmonella and Shigella are members of the Enterobacteriaceae and characterized by non-lactose
Commented [D4]: Move this section after methodology of the
review,
Besides, this part needs complete revision. Since the aim of this
study is to explore the global burden, therefore please specific to
like e.g. prevalence, morbidity, and mortality, etc.

fermenters, gram-negative rods, non-spore formers and facultative anaerobes (4). Shigella
species are non-motile, and non-gas producers(4, 5) and Salmonella species are motile, produces
acid and gas from glucose (4).

Members of the genus Salmonella are ubiquitous pathogens found in humans and livestock, wild
animals, reptiles, birds, insects(14). Salmonella is an important pathogen both for humans and
animals and causes severe infections (15). It causes infections in human and other vertebrates. It
is believed that it is an important cause of typhoid fever (enteric fever), gastrointestinal enteritis,
septicemia, and carrier states in human (4). It is a very complex group and contains more than
2000 species and typed on the basis of serotyping and species typing (6, 15).

The genusShigella encompasses four subgroups historically treated as species. Shigella species
are found only in the human intestinal tract (6) and are killed by drying (4). The natural habitat
of Shigella is limited to the intestinal tracts of humans and other primates, where they produce
bacillary dysentery. Shigellosis is an acute intestinal infection, the symptomsof which can range
from mild watery diarrhea to severeinflammatory bacillary dysentery (16).Shigella is similar to
enteroinvasiveEscherichia coli(EIEC) in that they both invade intestinal epithelial cells and
release Shiga toxin, which causes cell destruction(17).

Microscopically and culturally Shigella are indistinguishable from other enteric Gram-negative
bacilli (2 old,4).They are non-motile, non-capsulate and appear notto express fmbriae. Strains of
Shigella spp. Sharelipopolysaccharide (LPS) antigens with strains of E. coli but the LPS
structures are distinct and merelyshare common epitopes.The distinction between strains of
Shigella spp. AndE. coli depends on a limited number of diagnostic testsincluding motility,
production of lysine decarboxylaseand the utilization of citrate(4, 18).

3
2.2. Classification and nomenclature
Salmonella was first discovered and isolated from theintestines of pigs by Theobald Smith in
1855 and Dr Daniel Elmer Salmon take the discovery credit (15).The nomenclature of
Salmonellais controversial and still evolving. Currently, the CDC and WHO collaborating
centers classifies Salmonella species into two broad groups; Salmonellaenterica (type species)
and Salmonellabongori, based ondifferences in their 16S rRNA sequence analysis(14)

On the other hand, Kauffman and White developed a schemeto further classify Salmonella by
serotype based on threemajor antigenic determinants: somatic (O), capsular (K)and
flagella.Virulence (Vi)antigens, a special subtype of K antigen, are found only inthree
pathogenic serotypes: Paratyphi C, Dublin and Typhi.Salmonella(19).The genus Shigella is
subdivided on biochemical andserological grounds into four species.All strains express LPS
somatic antigens whichform the basis for the Shigella serotyping scheme.There are 13 serotypes
of which 4 of them are pathogenic (4).

2.3. Epidemiology
Shigellosis is one of the most common diarrheal diseases in humans worldwide. Shigellosis is
endemic throughout the world where it is held responsible for some 165 million cases of severe
dysentery (4).In the early 1980s, diarrheal disorders were the biggest child killers, responsible for
an estimated 4·6 million deaths worldwide every year(20). The incidences of Salmonella
infections in humans have dramatically increasedthroughout the world over the past few years
leading to its emergence as an important publichealth concern. S. enterica has become the
second most common bacterial cause of foodbornegastroenteritis cases worldwide(14).

According to the Centers for Disease Control and Prevention (CDC), approximately 42,000
salmonellosis cases are reported every year in theUnited States.Thus, every year, Salmonella
infection is estimatedto cause about 1.4 million human cases in the United States and to be the
leading cause of23,000 hospitalizations and 450 deaths from foodborne disease.The global
healthimpact is as high as an estimated 93.8 million illnesses and 155,000 deaths each year(21)

The devastating majority of these cases occur in the developing countries.Diarrhea was a
common cause of death among children under 5 years old (22).There are approximately 1.4
million cases of salmonellosis per year resulting in about 15,000 hospitalizations and 400 deaths
per year in the United States of America(23).2·5 million children still die from these illnesses

4
every year, almost all of them in developing countries(20).Diarrhea, however, remains a prolific
killer of children. Some data suggest that in children younger than 5 years it accounts for 15% of
cause-specific proportional mortality. The burden of diarrheal illness sits firmly in the
developing world, both for morbidity and mortality. Malnutrition andinadequate provision of
safe water, sanitation, and hygiene highlight the stark inequalities that exist within our world. A
quarter of children in developing countries are still malnourished1·1 billion people do not have
access to safe drinking water, and 2·4 billion are without adequate sanitation (4).

The epidemiology of salmonella and Shigella species depends on the country: S. flexneri is
predominant in developing countries, whilst S. sonnei is most reported in developed countries
(14). S. sonnei has become dominant in some Asian countries. Due to international travel and
trade of animals and food products, there is a shift in the prevalence of specific Shigella strain
types and serovars in different places (2, 7, 14).

Shigella species, continue to have an important global impact, causing an estimated 1 million
deaths and 163 million cases of dysentery annually.Shigellaspeciesare the most important causes
of acute bloody diarrhea (dysentery) and account for about 15% of all deathsattributable to
diarrhea in children younger than 5 years (20).Based on a research conducted for 3-year period,
in a web-based surveillance, Salmonella enterica serovarEnteritidis was by far the most common
serotype reported from human isolates globally. In 2002, it accounted for 65% of all isolates,
followed by S. Typhimurium at 12% and S. Newport at 4% (24). S. Enteritidis represented 85%
of isolates in Europe but only 9% in Oceania. In Latin America and the Caribbean, S. Typhi
accounted for the greatest proportion of salmonellae (13%) (9, 25). In Asia, from 2000 through
2002, Japan, Korea, and Thailand together reported S. Enteritidis as the most common human
serotype(26). In China, shigellosis is one of the top four notifiable infectious diseases, with 1.7
million episodes of bacillary dysentery, and 200,000 patients admitted to hospitals each year
(27).

Salmonella which has 2500 different serotypes is a leading cause of food borne infections
worldwide(28). 1.4 million Cases of food-borne salmonella disease have been reported in USA
alone (9). There is a slight increase (4.2%) compared with 1996 and a large increase compared
with 2005 (12.3%); this could be attributed to increased reports from several states, including
Texas and California (9, 24). In the same time in USA, the national incidence of laboratory

5
confirmed Shigella was 3.5 per 100,000 populations. This was isolated frequently from children
< 5 years of age, who accounted for 31.1% of all isolates (24).

In endemic regions of developing countries, salmonellosis and shigellosis are predominantly a

pediatric disease (24, 29). These diseases are important cause of morbidity and mortality
especially in children(30).More than one million deaths occur in the developing world yearly due
to Shigella infection (31).Estimates suggest that during the 1990s, nearly 1.4 billion diarrhea
episodes occurred every year among children younger than 5 years of age in socioeconomically
developing countries (32).

In developing countries, a number of studies report the high prevalence of salmonellosis and
shigellosis, especially in under 5- children. Higher infection rates of Salmonella have been
estimated in African countries annually (15).

In a recent study carried out in a pediatric hospital in the Democratic Republic of Congo,
among the 1,528 children included in the study, 26.8% were bacteremia and Salmonella
accounted for 59% of all bloodstream infections. In 1994, an explosive outbreak among
Rwandan refugees in Zaïre caused approximately 20,000 deaths during the first month alone.
Between 1999 and 2003, outbreaks were reported in Sierra Leone, Liberia, Guinea, Senegal,
Angola, the Central African Republic and the Democratic Republic of Congo (5). A study of the
etiological agents of childhood diarrhea in Lagos, Nigeria, reports a prevalence of Shigellaand
Salmonella was5.1% and 3.3% respectively(33)

The etiology and epidemiology of acute diarrheal disease on children in East Africa remain
largely undefined. As indicated in a research conducted in Dares Salaam,Tanzania, the
prevalence of Shigellaand Salmonellain under five children was 5.4% and 2.5%
respectively(34).A research from southern Libya points out a higher percentage of infection
(36%) by Salmonella species below 15 years of child age (35).

In Ethiopia, like other developing countries, salmonellosis and shigellosis are the common cause
of morbidity and mortality, particularly in children. According to a study conducted among
diarrheal patients at some selected health facilities in Addis Ababa, Ethiopia, the prevalence of
Shigella in stool samples was found to be 9.1%, and (3.9%) of children were found to be infected
with Salmonella species (13). According to a study conducted in the isolation rate of Shigella

6
species among diarrheal patients attending at HiwotFana Hospital, Harar, Ethiopia, the
prevalence of Shigella within 0-5 years of age was 17.7% (26). A research conducted in Jimma,
Ethiopia, from pediatric diarrheic outpatients, the prevalence of Salmonella species was 15.4%
(36). In a research conducted on the prevalence of Shigella among diarrheic children under-5
years of age attending at Mekelle health center, northern Ethiopia, showed a prevalence of 13.3
% (37).

According to a research conducted on biodiversity of Shigella isolates at Gondar university

hospital, northwest Ethiopia, reported that 58.5% of patients were 0-5 years old (38). In another
research from a five-year antimicrobial resistance pattern observed in shigella species isolated
from stool samples in Gondar University Hospital,northwest Ethiopia, report that children
accounted for more than a third (36.4%) of all Shigella positive patients(39).

2.4. Transmission
Typhoid (enteric fever) and Non-typhoidal Salmonella (NTS, e.g. food poisoning) is an
important public health problem worldwide. Shigellosis (bacillary dysentery), the result of
infection with Shigella, is one of the most common diarrhea-related causes of morbidity and
mortality in children under 5 years in developing countries (34). Around 95% of these cases are
caused by consumption of contaminated food products, and S. Enteritidis is responsible for at
least 15% of these cases (23).

Primarily salmonella and shigella transmitted through ingestion of contaminated food and
water(40) . Direct or indirect contact with infected animals and/or persons or from contact with
pets such as cats, dogs, rodents, reptiles, or amphibians can transmit the disease. Several recent
outbreaks have also been associated with consumption of contaminated plant products such as
sprouts, tomatoes, fruits, peanuts, and spinach(41) .

Children living in areas with poor sanitation are at higher risk for fecal-oral transmission. Food
and water contamination will result in a higher risk of acquiring infection caused by Salmonella
and Shigella(32).

2.5. Pathogenesis
Diarrhea poses a very serious problem in developing countries where it is the leading cause of
morbidity and mortality. As of other enteric bacteria salmonella and shigella species require a
mechanism to survive through the digestive tract and colonize a host and cause disease.
7
Salmonella species can infect both warm and cold-blooded hosts (4). By its ability of the
organism to avoid fusion of Salmonella containing vacuoles with dendritic cell lysosomes in the
intestine is the mechanism by which it can escape of killing. By surviving within macrophages,
Salmonella species will be carried to the spleen, lymph nodes and throughout the
reticuloendothelial system (6).

The severity of Salmonella infections in humans variesdepending on the serotype involved and
the health status ofthe human host. The number of bacteria that must be ingested to
causesymptomatic disease in healthy adults is 106-108nontyphoidSalmonella Organisms(42).
Children below the age of 5 years, elderlypeople and patients with immunosuppression are more
susceptible to Salmonella infection than healthy individuals(19).

When the bacteria enter thedigestive tract via contaminated water or food, they tendto penetrate
the epithelial cells lining the intestinal wall.SPIs encode for type III secretion systems, multi-
channelproteins that allow Salmonella to inject its effectors acrossthe intestinal epithelial cell
membrane into the cytoplasm.The bacterial effectors then activate the signal
transductionpathway and trigger reconstruction of the actin cytoskeleton of the host cell,
resulting in the outward extension orruffle of the epithelial cell membrane to engulf the bacteria.
The morphology of the membrane ruffle resembles theprocess of phagocytosis(19, 23).

Following theengulfment of Salmonella into the host cell, the bacteriumis encased in a
membrane compartment called a vacuole,which is composed of the host cell membrane. Under
normal circumstances, the presence of the bacterial foreignbody would activate the host cell
immune response, resulting in the fusion of the lysosomes and the secretion ofdigesting enzymes
to degrade the intracellular bacteria.However, Salmonella uses the type III secretion systemto
inject other effector proteins into the vacuole, causingthe alteration of the compartment structure.
The remodeled vacuole blocks the fusion of the lysosomes and thispermits the intracellular
survival and replication of the bacteria within the host cells. The capability of the bacteria
tosurvive within macrophages allows them to be carried in the reticuloendothelial system
(RES)(19).

Shigella is the leading cause of infant diarrhea and mortality (death) in developing countries. In
shigella the infective dose is small and causes bacillary dysentery (4, 11). It infects the M cells in
the Peyer’s patches of the large intestine. Strains ofShigella spp. are non-motile and it is not

8
known howthe bacteria reach and adhere to M cells. (4,5).The capacity of the bacteria to cross
the colonic mucosa via M cells associated with Gastrointestinal Associated Lymphoid Tissue
(GALT) and reprogram epithelial cells to produce pro-inflammatory mediators, such as
interleukin 8, which play a major role in the strong inflammatory response facilitating further
bacterial invasion. This triggers an intense acute inflammatory reaction with infiltration by
polymorph nuclear leukocytes. The shigella species cause bacillary dysentery leading to watery
or bloody diarrhea(40).Patients develop diarrhea because the inflamed colon, damaged by the
Shiga toxin, is unable to reabsorb fluids and electrolyte(17).

2.6. Virulence factors

The virulence factors of a pathogen are a multifactorial process that requires different general
class of determinants. Some of these are virulence genes that are required for physiological
process for survival in host and non-host environment (23). The second class of virulence genes
are unique to pathogenic organisms and these genes are rarely detected in non-pathogenic
organisms.Incorporation of a pathogenicity island can, in a singlestep, transform a normally
benign organism into a pathogen(19). Two pathogenicity islands have been identified in
Salmonella; the island at 63’ designated as SPI-1 which governs the ability of Salmonella to
invade epithelial cells and the second island at 31’designated SPI-2, mediates survival
withinmacrophages(43).The nucleotide sequence of the SPI-1 island iscompleteand includes at
least 25 genes, themajority of which encode components of a Type III secretion system and its
effector proteins. The SPI-2 island of Salmonella harbors at least 15 genesthat code for a distinct
Type III secretion systemand fora two-component regulatory system(23).

Shigella virulence is based on the presence of a large virulence invplasmid, carrying an operon
that encodes the type III-secretion-system (T3SS) responsible for bacterial entry. The T3SS is
composed of several proteins which connects the inner and outer bacterial membranes. As
indicated in a research in on Virulence Factors Associated with Pediatric Shigellosis in
BrazilianAmazon, all the isolates were positive for the ipaBCDgene, as expected, whereas
IpaB,IpaC, and IpaDare key factors of virulentShigella (16).Long-chain lipopolysaccharide
andthelipid A component playarole invirulence by preventing the effects of serum complement
and by causing localized cytokine release (4).

9
2.7. Clinical manifestations
Based on the clinical patterns in human salmonellosis,Salmonella strains can be grouped into
typhoid Salmonellaand non-typhoid Salmonella (NTS). In human infections, the four different
clinical manifestations are entericfever, gastroenteritis, bacteremia and other extra intestinal
complications, and chronic carrier state(19).

Human salmonellosis and shigellosis is usually characterized by acute onset of fever, abdominal
pain, diarrhea,nausea and sometimes vomiting(44). Typically, symptoms of gastroenteritis
developwithin 6 to 72 hours after ingestion of the bacteria. The symptoms are usually self-
limiting andtypically resolve within 2 to 7 days. In a small percentage of cases, septicemia and
invasiveinfections of organs and tissues can occur, leading to diseases such as osteomyelitis,
pneumonia,and meningitis(21). In some cases, particularly in the very young and in the elderly,
theassociated dehydration can become severe and life threatening. In such cases, as well as in
caseswhere Salmonella causes bloodstream infection, effective antimicrobials are essential drugs
fortreatment. Serious complications occur in a small proportion of cases (44). Althoughmost
cases are self-limiting, the degree to which a person becomes sick depends on his or herhealth
status and the number and virulence of Salmonella species ingested. In general, the poorerthe
individuals’ health and the more Salmonella ingested, the greater the probability for
seriousillness and death (14).

Of these Salmonella pathogens, most cause acute gastroenteritis, which is the mostcommon form
of salmonellosis. Also known as food poisoning, gastroenteritis ischaracterized by a short
incubation period and a predominance of an initial presentation ofsymptoms such as nausea,
vomiting, diarrhea, fever, headache, abdominal cramps, andmyalgias(4, 45)

Shigellosis clinical manifestations may vary fromasymptomatic to severe dysentery with several
complications.Infants were morecommon to have a history of non-bloody diarrhea,moderate to
severe dehydration, or bacteremia, butless common to have fever(46).

Shigellosis is an acute intestinal infection, the symptoms of which can range from mild watery
diarrhea to severe inflammatory bacillary dysentery (16). The most common symptom of
shigellosis is diarrhea, which often contains blood and mucusfrom the intestinal walls. Other
symptoms may include fever, nausea, vomiting, stomach cramps,tenesmus, dehydration and loss
of appetite. For young children, a fever and infection may lead toconvulsions. Some people may

10
remain asymptomatic (not develop symptoms) while infected.Symptoms usually appear 12 to 96
hours after infection (shigella).Aboutthree percent of people who are infected with S. flexneri
will develop Reiter’s Syndrome, which ischaracterized by joint pain, eye irritation and painful
urination. Reiter’s Syndrome can lastseveral months or years, and can lead to chronic arthritis,
but Reiter’s Syndrome only occurs when the person has a genetic predisposition to it(18, 47).

2.8. Diagnosis
Salmonellosis and shigellosis cannot be distinguished reliably from other causes of bloody
diarrhea on the basis of clinical features alone. Routine microscopy must be performed and the
presence of PMNs suggests a bacterial etiology but does not necessarily indicate salmonellosis or
shigellosis; it may be C. jejuni or diarrheagenic E. coli. To identify accurately culture and
biochemical tests must be performed. Blood culture and bone marrow aspirate may be used if the
source and trained personnel are available (17). The higher sensitivityof bone marrow cultures
compared to blood in part relates to the higherconcentration of organisms in bone marrow
(48)Molecular techniques are also more necessary to identify them correctly. The most common
methods currently in use are the pulse-field gel electrophoresis (PFGE) and multiple loci
sequencing typing (MLST) (4, 5, 17). The thirty isolates of Shigella species were confirmed by
conventional and 16S rRNA sequencing methods (16).

2.9. Treatment, prevention and control

Prevention of salmonellosis and shigellosis can be primarily on measures to control the spread of
the organism within the community.

1. Health education: - Teaching the child bearing mothers and school children about these
diseases and spreading the information in the local communities via health and religious
institutions, mass media, schools, and markets by using posters, drama etc.

2. Hand washing: - Hand-washing using soap is important after defecation, after cleaning a child
who has defecated, after disposing of a child’s stool, before preparing or handling food, and
before eating.

3. pure water supply: - The use of surface water for drinking, like water from a river, pond, or
open well, should be discouraged. To be used for drinking, it must be disinfected with chlorine
or it must be boiled.

11
4. breastfeeding: - breast feeding until 6 months must be promoted and continue breast feeding
with other nutrients for about 3 years are advisable.

5.Other prevention methods: -Other prevention methods should be promoted in the general
communities. In this regard health education must stress on the preparation and consumption of
safe food supply and on the disposal of environmental wastes.

Vaccine trials should be carried out to prevent it. But still there is no WHO recommended
vaccine that is effective in preventing shigella infections. Currently there is a trial against S.
flexneri but still it is under development (5). In other countries, heat-killed, phenol preserved
whole cell salmonella vaccines containing a mixture of culture of S. typhi and S.paratyphi have
been used. But these were not effective. Capsular (vi) polysaccharide replaces the existing
vaccine. Now oral live-attenuated salmonella vaccine is used (4, 17).

Antibiotics and use of oral rehydration therapy in developing countries has contributed
significantly to reduce mortality from diarrheal dehydration (4).

3. Significance of the review

Salmonellosis and Shigellosis are endemic in most developing countries and is the most
important cause of bloody diarrhea worldwide. There is a need to estimate the magnitude of the
global burden of disease and death caused by Shigella and Salmonella in children specially in
under 5- children (4). Several recent efforts are carried out in modern medical and public health
in controlling this global threat; the consequences of which are most devastating in the
developing world. Understanding the global burden of infections caused by entero-pathogens
particularly due to Salmonella and Shigella is essential to design effective control and preventive
strategies(5, 14).

4. Methods
4.1. Search strategies
Through computerized search using databases such as PubMed, goggle scholar, sci-hub and
different journal sites are assessed to download scientific papers around the world. Combination
of key words such as global burden of Shigella and Salmonella, diarrheal pediatric patients etc
are used to search journal articles.

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4.2. Study selection
Estimates suggest that during the 1990s, nearly 1.4 billion diarrhea episodes occurred every year
among children younger than 5 years of age in socio-economically developing countries, of
which 123.6 million episodes required outpatient medical care and 9 million episodes required
hospitalization. Children living in socioeconomically underdeveloped areas will have more
overall diarrhea episodes which are caused by enteric pathogens mainly by Salmonella and
Shigella. Severe episodes with dehydration and a higher death rate occur in children living in
more economically underdeveloped areas(32). Therefore, studying these deadly pathogens in
diarrheic pediatric population in Gondar, Ethiopia is crucial to have information for designing
strategies for preventing and controlling shigellosis and salmonellosis in diarrheic pediatric
patients in the area.

5. Conclusion
Globally, Salmonellae and Shigella infections remain a major public health threat and the
significant cause of morbidity and mortality especially in the pediatric population. Diarrhea-
causing pathogens are the second leading cause of morbidity and mortality worldwide; mainly
children under the age of 5 years are at high risk. The highest susceptibility of this age group
may be due to the fact that children less than 2 months old produce little hydrochloric acid
(gastric HCl), a natural barrier to many microorganisms.

The risk to salmonellosis and shigellosis is increased due to absence of effective vaccines,
modifying handwashing behavior after defecating to control prolonged community outbreaks and
identifying high-risk groups and targeting prevention measures. The widespread occurrences of
Salmonella and Shigella are attributed to several factors including malnutrition and under
nutrition, HIV-AIDS, the close relationship between man and animals, the widespread field
slaughtering practices, the raw meat consumption habits in some societies, the unhygienic food
handling practices and poor water sources.

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