CHAPTER I

INTRODUCTION

1.1

Background problem
diarrhea up to this point is still a major problem in society that are difficult

to resolve, from year to year diarrhoea remains one of the diseases that cause
mortality and malnutrition in children. According to the world health organization
(WHO) in 2009, diarrhea is the second leading cause of death in children under 5
years. Toddler death rate caused by diarrhea in indonesia is still classified as high
when compared to the Member countries of ASEAN, namely 3-4 times higher
than malaysia. Indonesia was ranked as the 6th highest after Singapore
(3/1000), Brunei Darussalam (8/1000), Malaysia (10/1000), Viet Nam (18/1000)
and Thailand (20/1000) (Sadikin, 2011).
for national scale based on the data from the Indonesian health profile in
2008, the year of diarrhea sufferers as much as 8443 people with diarrheal
mortality was 2.5%. This figure increased from the year before amounted to
1.7% with the number of diarrhea sufferers as much of 3661 people. in 2006 the
diarrhea sufferers in indonesia as much as 10280 people with a mortality rate
2.5%. in the hospitals of the province KEPRI Tanjung Pinang overall figures for the
incidence of acute diarrhea cases that come to the hospitals of the province
KEPRI by 2014 ranked 6 out of 10 most diseases each year or number four civil
defence emergency medical cases.
diarrhea is a condition in which occurs the frequency of abnormal
defecation, as well as changes in the content (more than 200gr/day) and a liquid
consistency (Brunner and Sudart, 2002). diarrhea is caused by many things
include bacteria, viruses, parasites, intolerance and drugs. According to the
World Gastroenterology Organisation global guideslines (2005) causes of
diarrhea from the bacteria that most often is the Eschericia Coli Pathogen,
Shigella sp, Salmonella sp, Vibrio Cholera, Pseudomonas SP, Staphylococcus
aureus, Streptococcus SP, and Klabsiella sp. a comparison of the percentage of
members of the genus shigella which causes dysentery are S. flexneri 70.6%, S.
Sonnei 17.6%, S. Boydii 5.9%, and S. Dysentriae 5.9%. members of the genus
shigella which has the highest percentage of as the cause of dysentery was
shigella flexneri (santoso et al, 2004).

Throughout the world, the incidence of shigelosis is estimated at 164.7

million cases each year, about 163 .2 million occurred in developing countries
and found 1.1 million people died. about 60% of the shigelosis incident occurred
in children less than 5 years. shigelosis incidence on developing countries is
nearly 20 times greater than that of the developed countries (WHO, in 2011).
Every year around 14,000 shigellosis cases reported in the United States,
due to the large number of mild cases are not diagnosed or reported, the number
of infections may be twenty times greater (CDC, 2009).
Shigella gathered in the ileum terminalis/colon, especially the distal colon,
the invasion of the intestinal mucosal epithelial cells, perform the multiplication
and spread intrasel and intersel then producing enterotoxin (a eksotoksin of
activities affecting the intestine, so it generally causes excessive secretion of
fluid into the gut cavity, causing diarrhoea and vomiting) as well as causing
increased cAMP, cAMP increased resulting in hipersekresi in bowel (diarrhea
liquid, diarrhea secretion).
In addition to producing enterotoxin, Shigella also produces eksotoksin
(Shiga toxin) which is cytotoxic cell infiltration resulting in inflammation, mucosal
epithelial cell necrosis occurs, erythrocytes and plasma out into the lumen of the
bowel so that feces are mixed blood (Santoso et al, 2009). as an enterotoxin,
these substances may cause diarrhea, as well as enterotoksisn in e. Coli. While
as a neurotoxin, a substance it contributed in causing the fatal nature of the
disease and the severity of infection of shigella dysentery as well as central
nerves cause reactions (meningismus, coma) (Jewetz et al, 2005). Shigella
flexneri is highly contagious and able to survive in the acidity of stomach
sufferers, through regulation of the genes resistant to acid. at a time when the
bacteria enters the body, then the adhesion is a mechanism of initial infection.
the bacteria enter the body must applies on the surface of hospes cells so that
the bacteria don't

carried liquid mucus or other fluids always moisten the

surface of the cell. bacterial bonding or adhesion depends on four factors,

namely contacts, dosages, frequencies affected, and absorption (Maia, 2008).
the contacts in a simple meaning that the host and microorganism must be
located close enough to cause an interaction. dose it mean number of
microorganisms that infect in the time allowed. the frequency is affected by the
length of time. While the absorption is the last factor that is important for an
organism to be attached to the surface of cells that infect (Maia, 2008).

Direct contact between the agent of infection with hospes begins with the
subsequent adhesion process form the colonization and infection occurred.
interactions between bacteria gram ngeatif with host cell played by structures
that are present on the surface of the bacteria i.e. fimbriae, flagella and outer
membrane component. the structure on the surface of it is an important
virulence factors in particular the ability to conduct adhesion and colonization on
channel cerna. adhesion to the surface of the host cell played by pili or outer
membrane protein (OMP) (Rozalski et al, 2007). characteristics of adhesion
molecule known through agglomerate ability of red blood cells.
The cell walls of gram-negative anaerobic bacteria including shigella
flexneri consists of two membranes, i.e. the membrane cytoplasmic or inner part
and OMP. OMP play an important role in the growth of the colonies, the formation
of biofilm and the progression of the disease (Yoshimura et al, 2009).
Outer membrane protein (OMP) is essential for the survival of anaerobic
gram-negative bacteria while in the macrophages and to invade eukaryotic cells
(Miller, 2001). OMP is located on the surface of gram-negative bacteria, the end
of the end is considered most important in inducing a specific immune response.
in the human digestive tract contains lymphoid tissue much like on the
spleen. the system of immunity in intestinal morphology and functional can be
divided into two main parts: (1) the tissue containing mucous follicles in groups
(GALT = Gut Associated Limphoid Tissue). (2) diffuse lymphoid tissue that are
widespread in the lamina propia of mucosa. on the first (GALT) lymphoid tissue is
incidental "afferent" ("afferent"): an antigen into the system and stimulate an
immune response, while the second (diffuse lymphoid tissue) is an area that is
"efferent" ("efferent"): antigen held interaction with cells that have differentiable
functions and cause the secretion of antibodies by B cells or cytotoxic reactions
elicited by T cells.
Outer membrane protein (OMP) from shigella flexneri acting as antigens
are transported to macrophages and presented it to the surface. This will trigger
T cells and B cells by releasing a variety of cytokines in the patch from payers.
After the stimulus, lymphoblasts will hold migration to mesenteric glands to
become more mature. from here limfoblast will enter the systemic circulation as
plasmablast to then put yourself along the surface of the intestinal mucosa and
producing as memory B cells or plasma cells IgA secretonic when there is
stimulation of antigen (Walker a. 2006). the same thing happened on T cell,

lymphocytes T exposed out of the patch of peyer, performing the migration and
become mature in the compartment of intestinal lymphocytes and other cells to
function as a regulator and effector cells (by Seidman e, 2005).
B cells that have been migrating to effector mucosa will undergo
differentiation into plasma cells which mengsekresi IgA antigen against which are
in GALT, and sekeresi IgA with mucous in other places.
aspects of mucosal immunity held by secretoric IgA (SIgA) (Brand-tzaeg,
2005). IG A was issued into the secretion with transport through ties to the
secretoric component (SC) can bind to antigens on the surface of the mucosal
antigen and thus be trapped in layers of mucus and experience the process of
degradation by Proteases. This most IgA are obtained in the secretion of the
external seromuccus from intestinal tract, respiratorik tract, urogenital tract,
tears, sweat, saliva and milk (Bowry, 2004).
Based on the classification, adhesion and hemoglutination, shigella
flexneri classified in type 1, which is able to perform that type of phili and
hemoglutination adhesion can be specifically inhibited by Mannose.
Fimbrae are considered functions helps the bacteria to survive and to
interact with the host. on pathogenic bacteria that cause infection, fimbrae and
other surface component can act as a specific adhesive factor, called adhesin.
Fimbrae bonding specificity can lead to bacteria stick to colonize a host on your
network and specific (Kusnadi, 2013).
Improper treatment on diarrhea will exert influence on the quality of life
for sufferers. oral rehydration therapy is proven to significantly lower the
mortality rate of diarrhea due to dehydration. but it turns out that this
intervention is just a little benefit for patients with diarrhea caused by an
invasive enteripathogen bacterial infections such as shigella.
The mortality rate caused by shigellosis in Indonesia and in the world still
high then require good treatment, therefore it's a diagnosis of diarrhea caused by
shigella spp should be accurate, i.e. the level of culture with an examination of
laboratory microbiology clinic and with test results is accompanied by sensitivity
to antibiotics. results culture requires a minimum of 3 days and this cannot be
shortened, for it takes the easy way, quickly and appropriately by conducting an
examination of serologis.

to speed up the treatment of sufferers required a short diagnostic test,

sensitive and specific. the diagnostic test will directly assist in providing
treatment to easily, quickly and precisely.
for this has been found some kits that the aim is to speed up diagnosis of
infectious diseases. one of the proteins used in the kit is the molecular adhesion.
Research getting that TB dot diagnosis tool quickly shows for a TB sufferer is
already marketed in indonesia and these tools contain components of molecular
adhesion m. tuberculosis that have a BM 38 kDa (Sugiri,2004). Molecular adhesis
sub unit of pili urophatogenic e. coli BM 32 and 66 kDa molecular adhesion sub
unit of pili (Mahdi,2009 abrar). A. baumanii BM 57.2 kDa has been reported to be
able to diagnose urinary tract infections caused by these two kinds of bacteria.
Sumarno (2012) also reported on the benefits of molecular adhesion sub unit of
pili BM 48 kDa s. Thypi who turns out to be used is also used for rapid diagnosis
of thypoid fever.
Sumarno et al. (2015) gets a sub Union pili protein hemagglutinin BM 49.8
kDa protein hemaglutination resistance and a sub unit of pili BM 7.9 kDa which is
a molecular adhesion. bacterial adhesion molecule can also be found on the OMP
bacteria, in research conducted by pore D et al. (2010) classify that OMP with BM
34 kDa is immune response specific to the bacterium shigella flexneri.
based on the above and because RSUD province KEPRI tanjung pinang is
not yet available examination of culture, to date it is unknown for certain types
of bacteria cause acute diarrhea then in this research will be conducted an
examination of molecular adhesion pili with BM, BM kDA 7.9 48.9 kDa and 34
KDa OMP shigella flexneri BM in people with shigellosis conducted of saliva and
serum dara sufferers as an attempt to diagnose the easily , quick and precise.

1.2 Problem identification

From the background of the problems that have been presented above,
emerging issues, namely:
1. How to profile the bacterial cause of diarrhea in RSUD province KEPRI
Tanjung Pinang?
2. What is the molecular adhesion sub unit of pili BM 7.9 kDa, BM 49,8 and
OMP BM 34 kDa

bacterial s. Flexneri has superior specificity and

sensitivity is good enough to diagnose shigelosis s. Flexneri ?

3. Whether the levels of IgA-S in Saliva equal to levels of IgA-S in blood on a

stool sufferers shigelosis s. Flexneri?

1.3 Research objectives

1.3.1 General Purpose
Assessing the potential for Diagnostic Molecular adhesion BM 7.9 kDA,
48.9 kDA

and OMP bacteria as the early diagnosis of shigelosis diarrhea

sufferers.
1.3.2 Special Purpose
1. Analyzing the profile of bacterial diarrhea sufferers in RSUD province
KEPRI Tanjung Pinang?
2. Analyzing the response of molecules adhesion sub unit of pili BM 7.9 kDa,
48.9 kDa and OMP BM 34 kDa shigella flexneri has a superior specificity
and sensitivity is good enough to diagnose shigellosis?
3. Analyzing IgA-S levels in saliva, blood and IgA-S on a stool sufferers
shigelosis S. Flexneri?

1.4 The Benefits of Research

The benefits of research are reviewed from several aspects, I.e the
science, community and applicability.
1.4.1 the benefits of the development of science
If the research is successful, then the research can get response molecules
adhesion sub unit of pili BM 7.9 kDa, BM 49,8 and OMP BM 34 kDa bacterial s.
Flexneri, which can be used as a tool of examination to diagnose quickly
sufferers shigellosis.
1.4.2 The benefits of applicability
For medical personnel: as a reference to improve the quality of health
services especially in diagnosing shigellosis.
1.4.3 Benefits for society

This research is very important for the community, because it can prevent
a high death rate due to diarrhea caused by shigellosis due to diagnostic tools
have found quick and precise.