Diare pada anak karena infeksi virus, bakteri, dan parasit

1. Acute Diarrhea
in Children
Alpha Fardah Athiyyah, Andy Darma,
Reza Ranuh, Subijanto MS
Gastroenterologi Division
Pediatric Department
Dr. Soetomo General Hospital Surabaya

2. Indonesian Pediatric Gastroenterology Institute
@pedgastroinstitute

3. Global causes of child (0-59 months) deaths in 2008
Black RE, Cousens S, Johnson HL et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010; 375:

6. Mortality and Diarrhea at
dr. Soetomo Hospital during 2007-2011
Divisi Gastroenterologi Ilmu
Kesehatan Anak, 2012
!
Number of Death
during 2007-2011

7. Definition : Diarrhea
• The passage of abnormally liquid or unformed stools
associated with increased frequency of defecation
• Increased frequency is defined by three or more bowel
movements a day
• A combination of frequency, stool consistency, and
stool weight should be taken into account for defining
diarrhea.
5/10/19 7

8. PHYSIOLOGY OF
INTESTINAL ABSORPTION

9. ABSORPTION
OF
NUTRITION

10. ABSORPTION
OF
CARBOHYDRATES

11. DISTURBANCES OF ELECTROLYTE
ABSORTION AND SECRETION

12. ABSORPTION OF SODIUM
• Na,K adenosine
triphosphate
(ATPase): Na
electrochemical
gradient
• Basolateral
membrane enzyme
• Nutrients
12

13. INTRACELULAR SECOND MESSENGERS
MEDIATOR OF SECRETION
• Cyclic adenosine
monophosphate
(cAMP)
• Cyclic guanosine
monophosphate
(cGMP)
• Ca/protein kinase C
13

14. Osmotic
• Lactase
def.
• Lactose
intol.
• Non
absorbable
substance
• Osmotic
effect
• Water
retained
• Large
volume
diarrhea
• Excessive
secretion
of fluid and
electrolyte
• Induced by
e.toxin,
hormone
produced
by tumor
• Large
volume
diarrhea
• Excessive
motility
• Decrease
o transit
time
o surface
mucosal
o Contact
o Absorptio
n
• Large volume
diarrhea
Secretoric Motile
PATHOPHYSIOLOGY OF
DIARRHEA
Inflammatory
• Infectious
pathogens
• Inflammatory
Bowel
Disease

15. • Occurs when :
o Nonabsorbable (mannitol, sorbitol, etc) / poorly absorbable solutes
(magnesium,
sulfates, and phosphates) are ingested
o Enterocytes or colonocytes cannot absorb the solutes (lactase
deficiencies)
• Happens in Viral diarrhea, Celiac disease and
Tropical sprue
• Stools are of less volume, acidic, reducing
substances, high osmolality > 2* Na + K.
• Stops with fasting , increased breath hydrogen with
malabsorption,no stool leukocytes.
Osmotic Diarrhea

16. Secretory Diarrhea
• Involves either net secretion of ions (chloride or
bicarbonate) or inhibition of net sodium absorption
• Net intestinal secretion -> secondary to the
stimulation of active chloride secretion and
inhibition of active absorption of sodium and
chloride by cyclic AMP
• Can arise from
o Gut lumen (by enterotoxins)
o Subepithelial space (by inflammatory mediators)
o Systemic circulation (peptide hormones produced from endocrine
tumors)
• Watery , large volume , normal osmolality( 2* Na+K )
• Persists during fasting,no stool leukocytes

17. • Common cause :
o Infection
• Disruption of the absorptive/secretary process of enterocyte
• Enterotoxins through an increase in cAMP, cGMP, or
increased intracellular Ca concentration and stimulate Cl
secretion in the small intestine
• Caused by :, ETEC, V. cholerae, Giardia, and Cryptosporidium
infections.
o Non infection, can be caused by :
• Peptide hormones (endocrine tumors)
• Gastrin secretion (Zollinger–Ellison syndrome)
• Acetylcholine, serotonin, and other modulators, such as
histamine in (systemic mastocytosis)
• Malabsorbed bile salts and fatty acids
• Inflammatory mediators (prostaglandins), which stimulate
colonic secretion (IBD)
• Small bowel bacterial overgrowth
• Congenital absence/alterations in transporters that maintain
the constant flux of the ions (congenital chloridorrhea,
congenital sodium diarrhea, and congenital bile acid
diarrhea)

18. Motility Diarrhea
• Increased motility :
• Decreased transit time.
• Stimulated by gastro-colic reflex
• Irritable bowel syndrome
• Thyrotoxicosis
• Post vagotomy
• Infections
• Decreased motility:
• Stasis : bacterial overgrowth.
• Pseudo-obstruction, blind loop

19. Inflammatory
• Inflammatory diarrhea may result from a wide variety of
etiologies, including infections and IBDs
• Infectious pathogens ->
o Cause disease by elaborating cytotoxins or by invading the
epithelium with resultant recruitment of inflammatory cells
o EAEC, EHEC, and C. Difficilex, Shigella, Campylobacter,
Salmonella, Yersinia, and E. histolytica
o Produce mucosal damage an stimulate intestinal
secretion.
o The products of the inflammatory reaction and the local
synthesis of inflammatory mediators contribute to mucosal
damage and intestinal
secretion
o Blood & increased WBCs in stool.

20. • IBD ->
o Cytokines and eicosanoids initiated by
inflammation downregulate the ion transporters
in the colon and small bowel resulting in Na
malabsorption
o Also bacterial proteins such as flagellin, further
the inflammatory milieu through the activation of
prochemotactic cytokines such as interleukin (IL)-
8.
o The intestinal epithelial cells may also secrete IL-6
that enhance neutrophil function and hence
further the inflammation

21. Etiology of Diarrhea
Infective
Non
infective
Viruses
Bacteria
Parasites
Fungi
Allergic
Symptomatic
Inappropriate feeding Food
intolerance
Climate

22. 5/10/19 22
Viral Enteropathogens
Viral enteropathogens cause most
illnesses in pediatric population.
n Rotavirus (more than 50% acute diarrhea)
n Astrovirus
n Norwalk virus
n Coronavirus
n Calicivirus
n Enteric adenovirus (serotypes 40 and 41)

23. 5/10/19 23
The most common cause of childhood diarrhea
second only to the viral enteropathogens
n Escherichia coli : EPEC; ETEC; EITC; EHEC; EAEC
n Campylobacter jejuni
n Shigella species
n Salmonella typhimurium
n Yersinia enterocolitica
n Staphylococcus aureus
n Clostridium difficile
n Vibrio cholerae
Bacterial Enteropathogens

24. 5/10/19 24
n Cryptosporidium parvum
n Entamoeba histolytic
n Giardia lamblia
Parasites Pathogens
Fungous Pathogens
n Candida albicans
n Aspergillus
n Mucor

25. Pathogens of Gastroenteritis
Pathogens Small Intestine Large Intestine
Bacteria C. perfringes
S. aureus
Aeromonas hydrophila
Bacillus cereus
(Salmonella)
(E. coli)
Campylobacter
C. difficile
E. coli (EHEC)
Salmonella spp.
Shigella spp.
Virus Rotavirus
Caliciviruses
Protozoa Giardia lamblia
Cryptosporidium
Cyclospora
Isospora
Entamoeba histolytica

26. Location, location, location…
Small Intestine Large Intestine
Pathogenesis Noninflammatory Inflammatory
Clinical Large volume stools
Watery, secretory
Small volume stools
Dysentery (bloody)

27. Diarrhea Causing Organism Divided according
to their mechanism of action
27
INVASIVE
PARTIALLY
INVASIVE
TOXICGENIC &
NON - INVASIVE
ADHERENT
Shigella species
Salmonella sp.
Y enterocilitica
C jejuni
V parahaemolitycus
E histolytica
Rotavirus
Norwalk Agent
Giardia Lamblia
Cryptosporidium
V cholerae
ETEC
A hydrophilis
EPEC
EPEC

28. Relative degree of
invasiveness of the
organisms causing diarrhea
• Lumen
• Mucosa
• Submucosa
28
Salmonella Shigella Rotavirus Cholera

29. Enteropathogen causing diarrhea
Dr. Soetomo hospital Surabaya - 2015
Pathogen Number of isolate Detection rate (%)
Adenovirus 40/41 5 8.5
Norovirus GII 31 52.5
Rotavirus A 49 83.1
Clostridium difficile (A/B toxins) 0 0
Campylobacter jejuni 5 8.5
Escherichia coli O157 0 0
Escherichia coli ETEC (LT/ST toxins) 14 23.7
Salmonella 2 19 32.2
Escherichia coli STEC (stx1/stx2 toxins) 0 0
Shigella spp. 7 11.9
Vibrio cholerae 0 0
Yersinia enterocolitica 0 0
Cryptosporidium spp. 17 28.8
Entamoeba histolytica 23 39.0
Giardia lamblia 15 25.4
29

30. New Recommendations on the
Management of Diarrhoea

31. VIRAL DIARRHEA

32. Highly contagious
SMALL infective dose
Up to 1011 viral
particles shed per gram
of stool
Shedding begins before
symptoms and persists
after illness
Stable in the
environment
Can survive on
hands for
HOURS; solid
surfaces for DAYS
Remains
infective
in stools for A
WEEK
Fischer TK et al Vaccine 2004; 22S:S49-S54, Dennehy PH Pediatr Infect Dis J 2000;19:S103–5; Linhares AC, Bresee JS. Pan Am J Pub Health 2000;8(5):305–
330; Parashar UD et al, Emerg Infect Dis 1998:4(4):561–570; Image: Ross hitaker/Getty Images
Rotavirus

33. Global Prevalence of Diarrheal
Rotavirus Infection
Tate JE et al. Lancet Infect Dis. 2012;12(2):136–141; Widdowson M, et al. J Infect Dis. 2009 .
<10 deaths per 100,000 children
10 to 50 deaths per 100,000 children
50 to 100 deaths per 100,000 children
100 to 1000 deaths per 100,000 children

34. Soenarto et al, The Journal of Infectious Diseases 2009; 200:S188–94
Palembang
60%
Jakarta
67%
Bandung
47% Yogyakarta
35%
Denpasar
59%
Mataram
63%
Median RV+:60%
Rotavirus diarrhea is disease burden in Indonesia
with most common in 6-23 months of age

35. Shell
Adapted from Kapikian AZ, Hoshino Y, Chanock RM. In: Knipe DM, Howley PM, Griffin DE, et al, eds. Fields
Virology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001
Inner Capsule
G Protein
P Protein
Outer Capsule:
Rotavirus Structure

36. Genotyping and clinical factors in pediatric diarrhea
caused by rotaviruses: one-year surveillance in
Surabaya, Indonesia

37. Subijanto, MS et al 2015

40. Pathogenesis of rotavirus
diarrhea
40
A. Mature enterocyte was infected
B. Virus multiplication è damaged after 24 hours
C. Crypt hypertrophy in 42 hours
D. Structure and function become normal in 15 days
(Barnes, 1991)

41. Clinical Manifestation
¨ Incubation period : < 48 hours
¨ Fever
¨ Nausea and vomiting
¨ Watery diarrhea
¨ Lethargy & irritable
¨ Respiratory symptoms
¨ Anorexia
¨ Lactose intolerance
¨ Dehydration and acidosis
¨ Serum electrolyte imbalance
41

42. Carlos CC et al. J Infect Dis 2009; 200 (Suppl 1): S174-81.
Characteristics Rotavirus-
positive
(n= 618), %
Rotavirus-
negative
(n= 2328), %
p
(x2 test)
Vomiting 79 53 <0.001
Fever 72 57 <0.001
Moderate &
severe
dehydration
72 59 <0.001
Intravenous
treatment
56 35 <0.001
Rate of hospital
admissions
35 22 <0.05
Clinical Presentation RV(+) vs. RV(-) GE

43. Rotavirus
• 2 infeksi alami memberikan perlindungan 100%
terhadap infeksi penyakit sedang/berat berikutnya
o Hampir 50% anak mengalami infeksi ketiga tetapi seluruhnya asimptomatik
atau dengan gejala ringan
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Probability
of
rotavirus
infection
1st infection
2nd infection
3rd infection
4th infection
5th infection
Moderate–severe
Mild–asymptomatic
Asymptomatic
or mild illness
Velázquez et al. N Engl J Med 1996; 335: 1022–8
Age (months)
Adapted with permission from Massachusetts Medical Society

44. Lactose intolerance &
Rotavirus
¨ Lactase = brush-border enzyme
¨ Rotavirus infection cause gut ephithelial
damage
¨ More severe in malnourished children
¨ Need elimination of lactose from the diet
¨ Longer time for recovery in malnourished
children
¨ Persistent diarrhea = post-enteritis syndrome
44

46. CLINICAL DIAGNOSIS
• Age : 6-24 months
• Watery diarrhea, > 10 times/day
• Vomitting
• Fever
• Respiratory symptoms
• Lactose intolerence
• Dehydration
46

47. Laboratory Diagnosis
• Antigen detection of the
virus in stool specimens
­ Immunological assays (ELISA)
confirm the precence of a viral
capsid protein
­ Characteristic wheel shape of virus
identified by electron microscopy
of stool specimens
47

48. 48
rezaranuhS2tropik2017
Key Management Strategies1
• Oral Rehydration Solutions
• Exclusive breastfeeding
• Vitamin A supplementation
• Hand washing with soap, improved quality water, and access
to sanitation
o More strategies are now available with even greater potential:
• Zinc supplementation
• Rotavirus vaccines, with the recent recommendation from
WHO to include in immunization programs, have the potential
to save 2.5 million lives by 20253
1. Fischer Walker CL et al. PLoS Med. 2011;8(3):1–10. 2. UNICEF/WHO. Diarrhoea: Why children are dying and what can be done.
http://www.who.int/child_adolescent_health/documents/9789241598415/en/index.html. Accessed February 15, 2012. 3. Atherly D et al. J Infect Dis. 2009;
200(suppl1):S28–S38.

50. Diarrhea
Gastrointestinal
Mucosal Defense
Bacterial Virus
Hygiene/Sanitation
Normal Flora Vaccination
Malnutrition

51. SHIGELLA INFECTION

52. Shigella Infection

53. Shigellosis - Epidemiology
• Four species of Shigella: flexneri, sonnei, dysenteriae,
boydii
• Major public health problem in many developing
countries
o causes about 5 to I0% of childhood diarrhoea
o up to 25% of all diarrhea-related deaths can be
associated with Shigella

54. Shigellosis - Epidemiology
• Worldwide distribution; infections occur throughout year
• Mostly in children aged under five
• Rates of infection are highest where sanitation is poor
• As few as 10 cell can initiate infection
• Transmission influenced by:
o nutritional status
o environmental factors affecting transmission:
• rainfall and temperature
• Waterwashed as well as waterborne

55. Shigella and Shigellosis
• Fecal-oral transmission
• person-to-person, fomites, food, water, etc.
• Waterborne and water-washed
• Reservoirs: humans and primates
• Infectious dose: low; as few as 10 cells to infect
• Incubation period: 1 to 7 days; typically, 1-3
• Duration of illness:
• untreated: severe symptoms for about two weeks
• Antibiotic treatment shortens illness and prevent
spread to others

56. Shigellosis - Illness
• Persistent diarrhea with frequent and painful passage of
stools consisting mostly of blood, mucus and pus
o accompanied by fever and stomach cramps.
• Shigella infect, invade cells lining the large intestine (colon)
• Cause breaks (ulcers) in mucous membrane lining of intestine
o Inflammation and tissue damage
o Causes painful straining to pass stools; can lead to rectal
prolapse
o Ulcers commonly in the rectum
o results in increased production of mucus
o loss of blood and serum proteins into intestinal cavity
• Causes the symptoms of dysentery, which include blood and
mucus in the stool (bloody diarrhea); fever is also common

57. RISK GROUPS
• Children aged 1–4 years living in resource-restricted
settings
• Travellers to endemic areas
• MSM (Males who have Sex with Males)
• Children in daycare and their household contacts

58. INCUBATION AND
TRANSMISSION
• Incubation period
o 1–4 days, up to 8 days with S dysenteriae type
• Transmission
o Primarily person-to-person because of the low infectious inoculum
o Food and waterborne, or can initiate outbreaks that are propagated by
person-to-person spread
o Flies can disseminate in settings with faecal
contamination of the environment

59. CLINICAL PICTURE
Symptoms begin with sudden onset of high-
grade fever, abdominal cramps & watery diarrhea
Subsequently the diarrhea became mucoid,
of small volume & mixed with blood. This is
accompanied by abdominal pain, tenesmus &
urgency. Fecal incontinence may occur.
Physical signs are those of dehydration
beside fever, lower abdominal tenderness &
normal or increased bowel sounds.

60. LAB FINDINGS
Stool microscopy reveals presence of RBC &
pus cells with mucous
Culture of fresh stool in MacConkey agar will
grow shigella in 80% of cases.
WBC is usually normal but leukocytosis or
leukopenia may occur. Platelets are on the
lower normal range.

61. MORTALITY & MORBIDITY
Whereas mortality caused by shigellosis is
rare in western countries, it is associated with
significant mortality & morbidity in developing
world.
Dehydration is the most common
complication of shigellosis, but serious
gastrointestinal & systemic complications
may occur.

62. Rectal prolapse
Mild Hepatitis
Toxic mega colon
GASTROINTESTINAL RISKS
Septicemia particularly in children with PEM

63. q These include:
Lethargy, delirium, meningismus & seizures
Encephalopathy (rare & may be lethal)
Syndrome of inappropriate ADH secretion
Febrile seizures
NEUROLOGICAL COMPLICATIONS

64. SYSTEMIC COMPLICATIONS
Hemolytic uremic syndrome
Disseminated intravascular coagulation (DIC)
Reiter syndrome, arthritis, conjunctivitis & urethritis
Myocarditis

65. DIFFERENTIAL DIAGNOSIS
Amebiasis
Yersinia Entrocolitica infection
Campylobacter infection
Salmonellosis
Escherichia Coli infection
Crohn disease
Ulcerative colitis
Clostridium difficile infection

66. Amoeba Basillar
Epidemiology Chronic-End. Acute, Epid.
Incubation Long < 1 week
Age All age Children (usually)
Clinical condition Walking dys Lying down dys
Fatality
Defecation 6 – 8/day 10x/day
Amount of Feces Relatively few Many
Colour Dark red Fresh red
Consistency Mucous doesn’t stick
to the container
viscous stick on the
bottom of container
Reaction acid base
RBC aggregate Separate
Macrophage Few
Eosinofil Rarely found
Basofil -
Ch. Leyden Kr + -
Parasites + -

67. THERAPY

69. ENTAMOEBA HISTOLYTICA

70. Ameba:
Entamoeba histolytica
Entamoeba dispar
Entamoeba coli
Entamoeba hartmanni
Endolimax nana
Iodamoeba bütschlii
Flagellates:
• Giardia lamblia
• Dientamoeba fragilis
• Chilomastix mesnili
• Trichomonas hominis
• Trichomonas vaginalis
•(other body sites)
• Enteromonas hominis
• Retortamonas intestinalis
Apicomplexa:
• Cryptosporidium hominis
• Cryptosporidium parvum
Other:
• Blastocystis hominis
• Balantidium coli
INTESTINAL PROTOZOA
unicellular eukaryotic organisms

72. Fecal-Oral Transmission Factors
•poor personal hygiene
• food handlers
• institutions
• children in day care centers
•developing countries
• highly endemic
• poor sanitation
• travelers diarrhea
•water-borne epidemics
•zoonosis
• Entamoeba = no
• Cryptosporidium = yes
• Giardia = controversial
Control/Prevention
• improve personal hygiene
• especially institutions
• treat asymptomatic carriers
• eg, family members
• health education
• hand-washing
• sanitation
• food handling
• protect water supply
• treat water if questionable
• boiling
• iodine
• not chlorine

73. Amoebiasis
• Amoebiasis is caused by Entamoeba histolytica .
• The organism formerly known as E .histolytica is now
known to consist of two distinct species :E .histolytica ,which
is pathogenic, and E .dispar ,which is non-pathogenic.
• Cysts of the two species are identical, but can be
distinguished by molecular techniques after culture of the
trophozoite .E .histolytica can be distinguished from all
amoebae except E .dispar ,and from other intestinal
protozoa, by microscopic appearance .
• Amoebiasis occurs world-wide, although much higher
incidence rates are found in the tropics and subtropics .

74. Cont.
• The organism exists both as a motile trophozoite and as a
cyst that can survive outside the body.
• Cysts are transmitted by ingestion of contaminated food
or water, or spread directly by person-to-person contact .
• Trophozoites emerge from the cysts in the small intestine
and then pass on to the colon, where they multiply .

76. Clinical features
• Individuals can carry the pathogen without obvious Many
evidence of clinical disease )asymptomatic cyst passers
• This is may be due in some cases to the misidentification
of non-pathogenic E. dispar as E. histolytica, and it is not
clear how often true E. histolytica infection is
symptomless.
• In affected people E. histolytica trophozoites invade the
colonic epithelium, probably with the aid of their own
cytotoxins and proteolytic enzymes.

77. Cont.
• The parasites continue to multiply and finally frank ulceration
of the mucosa occurs .
• If penetration continues, trophozoites may enter the portal
vein, via which they reach the liver and cause intrahepatic
abscesses .
• This invasive form of the disease is serious and may even be
fatal .

78. Incubation period
• The incubation period of intestinal amoebiasis is highly
variable and may be as short as a few days or as long
as several months.
• The usual course is chronic, with mild intermittent
diarrhoea and abdominal discomfort. This may progress
to bloody diarrhoea with mucus, and is sometimes
accompanied by systemic symptoms such as headache,
nausea and anorexia.
• Less commonly, infection may present as acute amoebic
dysentery, resembling bacillary dysentery or acute
ulcerative colitis.

79. Complications
• Complications are unusual, but include toxic dilatation of
the colon, chronic infection with stricture formation,
severe haemorrhage, amoeboma, and amoebic liver
abscess.
• Amoebomas, which develop most commonly in the caecum
or rectosigmoid region, are sometimes mistaken for
carcinoma. They may bleed, cause obstruction or
intussuscept.
• Amoebic liver abscesses often develop in the absence of
a recent episode of colitis. Tender hepatomegaly, a high
swinging fever and profound malaise are characteristic,
although early in the course of the disease both symptoms
and signs may be minimal.

80. Diagnosis
• Microscopic examination of fresh stool or colonic exudate
obtained at sigmoidoscopy is the simplest way of
diagnosing colonic amoebic infection.
• To confirm the diagnosis motile trophozoites containing
red blood cells must be identified: the presence of
amoebic cysts alone does not imply disease.
Sigmoidoscopy and barium enema examination may show
colonic ulceration but are rarely diagnostic.
• The amoebic fluorescent antibody test is positive in at
least 90% of patients with liver abscess and in 60-70%
with active colitis. Seropositivity is low in asymptomatic
cyst passers.

81. Management
• Metronidazole is a drug of choice
• Tinidazole is also effective: dehydroemetine and
chloroquine are alternative drugs, but are rarely used.
After treatment of the invasive disease, the bowel should
be cleared of parasites with a luminal amoebicide such
as diloxanide furoate.

82. Prevention
• Amoebiasis is difficult to eradicate because of the substantial
human reservoir of infection. The only progress will be through
improved standards of hygiene and better access to clean
water.
• Cysts are destroyed by boiling, but chlorine and iodine
sterilizing tablets are not always effective.

83. Amoeba Basillar
Epidemiology Chronic-End. Acute, Epid.
Incubation Long 1 week
Age All age Children (usually)
Clinical condition Walking dys Lying down dys
Fatality
Defecation 6 – 8/day 10x/day
Amount of Feces Relatively few Many
Colour Dark red Fresh red
Consistency Mucous doesn’t stick
to the container
viscous stick on the
bottom of container
Reaction acid base
RBC aggregate Separate
Macrophage Few
Eosinofil Rarely found
Basofil -
Ch. Leyden Kr + -
Parasites + -

84. GIARDIA LAMBLIA

85. Intestinal Parasitic Infestations
Protozoa
Giardia lamblia (Giardiasis)
• A flagellated protozoan
• Infects the duodenum and upper part of the small
intestine
• Infection is often asymptometic but can be associated
with a variety of intestinal manifestations

86. Giardia lamblia

87. Giardia lamblia

88. • Infection occurs by the ingestion of cysts
in contaminated water or food.
• In the small intestine, excystation
releases trophozoites that multiply by
longitudinal binary fission.
• The trophozoites remain in the lumen of
the proximal small bowel where they
can be free or attached to the mucosa
by a ventral sucking disk.
• Encystation occurs when the parasites
transit toward the colon, and cysts
are the stage found in normal (non
diarrheal) feces.
• The cysts are hardy, can survive several
months in cold water, and are
responsible for transmission.
• Because the cysts are infectious when
passed in the stool or shortly afterward,
person-to-person transmission is
possible.
• While animals are infected with Giardia,
their importance as a reservoir is
unclear.

89. Giardia lamblia

90. In wet mounts, cysts show the typical ovoid ellipsoid shape
measuring from 8-19 mm (range 11-14 mm)

91. Giardia trophozoite
(Trichrome stain x 1000)

92. Giardia lamblia
• 10-25 cysts sufficient to initiate infection
• Colonization à morphologic damage to
intestinal epihelial cells and brush border
may result in
normal microvilli or subtotal atrophy
o Disaccharidase deficiencies (usually lactase)
o Malabsorption affecting protein fat-soluble vitamines
o Decreased intestinal absorption of antibiotics

93. Giardia lamblia
• Cysts viable for 3 months in water at 4o C
• Freezing does not eliminate infectivity completely
• Heating, drying and sea water are likely to do
so
• Human milk is lethal to Giardia trophozoites
through the action of fatty acids
• Duodenal fluid is also lethal to Giardia
• Survival in hostile environment is attributed to the
protective effect of human mucus

94. Giardia lamblia
¨ Anti-Giardia IgG is found in 80% of patients during
symptomatic infection
¨ Anti-Giardia IgG tends to persist, thus limiting
usefulness in distinguishing current from past
infection
¨ Serum anti-Giardia IgM antibodies increase early in
infection and decrease rapidly after 2-3 weeks
¨ Human milk protection against Giardia correlates with
anti-Giardia serum IgA

95. Epidemiology
• Occurs worldwide
• Age-specific prevalence:
o Highest in children 0-5 years
o Followed by 31-40 years old
• Most cases reported in late summer and early fall
• Transmission is common in certain high risk populations:
o Children and employees in DCCs
o Consumers of contaminated water
o Travelers to certain areas of the world
o Those exposed to domestic and wild animals (dogs, cats, cattle deer, and
beaver)

96. Epidemiology
• Major reservoir/vehicle for spread: Water
contaminated with cysts
• Major risk for hikers:
Drinking untreated mountain stream water
• Person-to-person spread: Frequent
in areas of low hygienic standards/crowding
• Person-to-person spread occurs in:
o Childcare centers
o Families of children with diarrhea

97. Clinical Manifestations
Symptom Percent
Diarrhea 64-100
Malaise. Weakness 72-97
Abdominal distension 42-97
Flatulance 35-97
Abdominal cramps 44-81
Nausea 14-79
Foul-smelling, greasy stools 15-79
Anorexia 41-73
Weight loss 53-73
Vomiting 14-35
Fever 0-28
Constipation 0-17

98. Clinical Manifestations
• Symptoms vary with age
• Profuse watery stools à greasy, foul smelling, buoyant
• Blood, mucus fecal leukocyte are absent
• Varying degrees of malabsorption can occur
• Abnormal stool patterns can alternate with constipation
and normal bowel movements
• Infrequent associations: reactive arthritis, urticaria

99. Clinical Manifestations
¨ Asymptomatic carriers in USA: 3%-7%
(up to 20% in southern regions)
¨ Prevalence studies in DCC children 36 months: 21%
¨ Asymptomatic infection is well tolerated
¨ Testing of case contacts/treatment of asymptomatically
infected individuals is NOT indicated routinely
¨ Humoral immunodeficienies (hypo-,
agammaglobulinemia) predispose to chronic
symptomatic giardiasis

100. Diagnosis
Definitive Diagnosis:
Detection of trophzoites, cysts or antigens in stool or duodenal fluid
• Stool specimens:
Examined within 1 hour after being passed or should be
stored in vials containing polyvinyl alcohol (PVA) or 10% formalin
o Trophozoites are more likely to be found in unformed stools
(rapid transit time)
o Cysts, but not trophozoites, are stable outside the GI tract
• Duodenal Specimens:
Aspirate/Biopsy à Trophozoites can be seen on direct wet mount

101. Diagnosis
Microscopy:
Diagnostic: 70% of patients with single exam
85% with a second exam
Antigen Detection:
(Polyclonal antisera or monoclonal antibodies)
EIA: 87%-100% sensitivity / 100% specificity
DFA: 100% sensitivity/specificity
Giardiasis is NOT associated with eosinophilia

102. Treatment
Oral Antimicrobial Therapy for Giardiasis
Agent Pediatric Dose Adult Dose
Metronidazole 15 mg/k/d divided in 3 doses X 5d 250 mg tid X 5d
(Flagyl)
Furazolidone 6 mg/k/d divided in 3-4 doses X 10d 100 mg tid X 10d
(Furoxone)
Albendazole 400 mg/day X 5d 400 mg/day X 5d
(Albenza)
Quinacrine 6 mg/k/d divided in 3 doses X 5d 100 mg tid X 5d
(Atabrine)
Nitazoxanide 12-47 mo: 100 mg bid X 3d N/A
(Alinia) 4-11 yrs: 200 mg bid X 3d
(100 mg/5 ml)

103. Prevention
• Strict hand washing after contact with feces
• Purification of public water supplies
• Chlorination
• Sedimentation
• Filtration
• Avoid swallowing: recreational water, water from shallow
wells, lakes, rivers, streams, ponds springs
• Travelers to endemic areas: avoid drinking untreated
water uncooked foods that have been grown, washed
or prepared in potentially contaminated water
• Purification of drinking water: Heating (55o C X 5 min) or
use filter (pore size 1 um)

104. SALMONELLOSIS

105. • Most common serotypes :
• Salmonella enteritidis
• Salmonella heidelberg,
• Salmonella newport,
• Salmonella typhimurium,
• Salmonella typhi.
• Cause two distinct clinical syndromes: enterocolitis
(nontyphoidal serotypes) and typhoid fever (S.
typhi).

106. NON TYPHOIDAL SALMONELLA
GASTROENTERITIS
• Nontyphoidal Salmonella gastroenteritis is a major cause of
bacterial diarrhea in the USA with over 1 million cases
estimated yearly
• Commonly caused by contaminated foods such as poultry,
egg yolks, fresh produce, ground beef, and milk
• Antibiotics contribute to adverse public health consequences
such as prolonged shedding, increased likelihood of a carrier
state and emergence of resistant strains
• Antibiotic therapy is indicated for severe symptoms, systemic
disease, and patients with severe comorbid conditions or risk
factors for invasive infection.
• Treatment of severe disease :
• Fluoroquinolones or ceftriaxone;
• Azithromycin

107. TYPHOID FEVER
• Caused by S. typhi
• Symptoms occur in four distinct stages each lasting
about 1 week:
• Nonspecific symptoms (including fevers and chills),
• Right lower quadrant pain with diarrhea and rose spots,
• Complications of infection, and (4) resolution of illness.
• Diagnosis : blood culture early in the course of illness
or stool culture late in the course.
• Treatment : fluoroquinolones

109. 5/10/19
109
Anatomy of the Gut
• Mucosa
• Submucosa
• Muscularis
• Serosa
• Regional variations ?

110. Gastrointestinal
Tract’s
Structure

111. 5/10/19
111
Regional Variations in the Gut
• Submucosa can contain
lymphoid tissue:
o Eg: Peyers Patches in the
Ileum
o Function?

112. 5/10/19 112
Specialized Secretory Structures
Small
Intestine
Large
Intestine

113. 113

116. Enteric pathogens causing Acute Diarrhea in
Children
Dr. Soetomo General Hospital Surabaya (year 2000)
0
5
10
15
20
25
30
35
40
45
Rotavirus
Rotavirus-
DE.coli
Shigella
Salmonella
V.cholerae
%
Tropical Disease Center Airlangga University 2002

118. Model of Rotavirus induced Diarrhea

119. Model of Rotavirus induced Diarrhea

126. Subijanto, MS et al 2015

127. Subijanto, MS et al 2015

128. 1. Genotype G2P[4] has the highest prevalence.
2. G3, G4 and G9 and G2P[4] combination
genotype were found to be associated with
severe and frequent diarrhea.
3. Further long-term studies as well as
surveillance programs are necessary for
overcoming rotaviral disease.
Subijanto, MS et al 2015

130. Highly contagious
SMALL
infective
dose
Rotavirus stable in the environment
Can survive on hands FOR HOURS;
on solid surfaces FOR DAYS
Remains stable and infective
in stools FOR A WEEK

131. Dennehy PH. Pediatr Infect Dis J 2000; 19: S103-5.
None of the disinfectants commonly used for hand washing
completely inactivate RV in the normal hand washing time
Recommendation
Hand washing BEFORE AND AFTER contact with
infected children using alcohol-based
waterless hand-cleansing agent

133. • No dehydration Mild-Moderate
dehydration : Standard formula
• Severe dehydration : Free lactose formula
• No dehydration and Mild-Moderate
dehydration with severe lactose intolerance
: Free lactose formula
Special formula ?

134. Prevention

139. WHO Recommendations
(June/December 2009)
• Rotavirus Virus (RV) vaccination should be
included in all national immunisation
programmes for all infants
• Widespread RV vaccination in Asia has a huge
potential public health impact
WHO . Weekly Epidemiol Rec Dec 2009; 84, 533–540 ; Nelson EA., et al. Vaccine 2008; 26
(26): 3192–6; PATH.2009: available from
http://www.path.org/files/IMM_rotavirus_briefing.pdf

141. Cellular pathogenesis of Shigella spp.
Schroeder G N , and Hilbi H Clin. Microbiol. Rev.
2008;21:134-156

142. Genetic events contributing to the evolution of Shigella spp. from nonpathogenic E. coli
ancestors.
Schroeder G N , and Hilbi H Clin. Microbiol. Rev.
2008;21:134-156

143. Regulatory elements controlling the expression of the T3SS and its substrates on the S.
flexneri virulence plasmid.
Schroeder G N , and Hilbi H Clin. Microbiol. Rev.
2008;21:134-156

144. Architecture of the S. flexneri Mxi-Spa T3SS.
Schroeder G N , and Hilbi H Clin. Microbiol. Rev.
2008;21:134-156

146. Virulence in shigella species is determined by
chromosomal plasmid-coded genes.
VIRULENCE
Shigella invades colonic mucosa causes
cell necrosis using both virulent agents.
Chromosomal genes control cell wall antigens
that are resistant to host defense mechanisms.
Plasmid genes control production of cytotoxin
and siderophores. The cytotoxins are both
enetrotoxic and neurotoxic.

147. Management of Diarrhea

148. Global Diarrhoea Treatment Policy
• Treatment of dehydration with ORS solution (or with an intravenous
electrolyte solution in cases of severe dehydration)
• Provide children with 20mg per day of zinc for 10-14 days
• Continue feeding or increase breastfeeding during, and increase
feeding after the diarrhoeal episode
• Use antibiotics only when appropriate (i.e. bloody diarrhoea and
cholera) and abstain from administering anti-diarrhoeal drugs
(including probiotics)
• Advise mothers on danger signs and on compliance with the
treatments
WHO/UNICEF. Joint statement on the clinical management of acute
diarrhoea. 2004.

149. 1. Rehydration
• According to dehydration degree
– No dehydration à Treatment Plan A
o Some dehydration à Treatment Plan B
o Severe dehydration à Treatment Plan C

150. • A child’s fluid deficit can be assessed as follows ;

155. Reduced Osmolarity
ORS Solution
• Stool output is reduced by 25 to 30%
• Vomiting is reduced by 30%, and
• The need for unscheduled IV fluids is reduced by more
than 35%

156. The Molecular process of
ORT

157. Plan
Degree of dehydration Estimation of fluid Type of
solution
Route of treatment
A Normovolemia 10-20
ml/kg/diarrhea
ORS oral
B Moderate 6-9%
Mild
70ml/kg/3h
50ml/kg/3h
HSD/ORS
HSD/ORS
Iv/intra gastric
Oral/iv/intragastric
C Severe 30ml/kg/1h Ringer
Lactate
iv
Pediatric Fluid Rehydration (iso-hyponatremia)
Soetomo Hospital
Neo/3 Mo : D10%0,18 NaCl
Bronchopnemonia, Severe Malnutrition, heart failure : 30ml/kg/2h ; Mild :70ml/kg/6h
Hypernatremia : HSD 320ml/kh/48h
Pediatric Standard Therapy of Soetomo Hospital 2008

158. Pediatric Fluid Therapy Principles
Maintenance H2O needs:
Weight in Kg H2O fluid needs
1-10 100cc /kg /day
11-20 1000+50cc/kg/day
20 1500 + 20cc/kg/day
Add 12 % for every 0C

160. 16
0

161. Severe Malnutrition
• Do not use the IV route for rehydration except in
cases of shock
• ReSoMal 5ml/kg/30 minutes for first 2 hrs ; then 5-
10 ml/kg/h for the next 4-10 hrs
• ReSoMal : 37.5mmol Na, 40mmol K and 3 mmol
Mg per litre

162. Severe Malnutrition

164. Severe Malnutrition

165. Severe Malnutrition

166. 2. Nutritional Support
• The infant usual diet should be continued during
diarrhea and increased afterwards
• Food should never be withheld
• The child's usual foods should not be diluted
• Breastfeeding should always be continued.
• Aim : to give as much nutrient rich food as the child
will accept
• When food is given, sufficient nutrients are usually
absorbed to support continued growth and weight
gain.
• Continued feeding speeds the recovery of normal
intestinal function

167. 3. Zinc Supplementation
• Zinc supplementation
o Reduce duration and severity of the diarrheal episode
o Reduce the risk of dehydration
o Prevent diarrhea from relapsing in 2-3 months
– Restore child’s appetite
• Dosage
– 6 months : 10 mg per day
o 6 months : 20 mg per day
• Given for 10-14 days straight (although the child has
recovered from diarrhea)

168. Mechanisms of Action of ZINC
• Booster effect on immune function: Zinc
is the main-cofactor of immune function
enzymes
• Anti-Secretory effect: Zinc acts as a K
channel blocker of cAMP mediated
chlorine secretion, leading to increased
absorption of Na+ et reduced secretion
of Cl
• Anti-oxydative effect: maintenance of

169. Low
Inter-
mediate
High
~33% of the worlds population
live in countries with a high risk
of zinc deficiency
Zinc Defiency
Low
Inter-
mediate
High

170. Zinc for the Treatment of Diarrhoea
Research Findings
• 20% reduction in duration of acute diarrhoea
• Significant reduction in diarrhoea severity
• 24% reduction in duration of persistent diarrhoea
• 42% reduction in treatment failure or death in
persistent diarrhoea

171. Additional Preventive Aspects of Zinc
Treatment
• Zinc supplementation for 10-14 has longer term effects
on childhood illnesses in the 2-3 months after treatment
• 34% reduction in prevalence of diarrhoea
• 26% reduction in incidence of pneumonia
• Zinc Dose : 6 Mo (10mg) for 10 days
• 6 Mo (20 mg)
• Zinc Investigators Collaborative Group. Pediatrics. 1999.

172. 4. Selective Antibiotic
• Indication :
bloody diarrhea (dysentry) and cholera
• Dysentry
Give antibiotic for 5 days

173. WHO
§ Quinolon (e.g. Ciprofloxacin) 30-50 mg/kg body weight/day divided in 3
dosages for 5 days
§ Monitor in 2 days :
fever, reduced diarrhea, blood in stool, increased appetite
§ improvement à STOP THE ANTIBIOTICS
§ no improvement à stop the antibiotic and replace it with a more
suitable antibiotic (according to the area and sensitivity)
§ If still no improvement, other etiology should be considered

174. 5. Parents’ Education
• Parents should take their child to a health worker if
the child:
o starts to pass many watery stools;
o has repeated vomiting;
o becomes very thirsty;
o is eating or drinking poorly;
o develops a fever;
o has blood in the stool; or
o the child does not get better in three days.

175. PROBIOTICS

176. Effect of Probiotics to Prevent Diarrhoea
• Statistically significant effect on
o Antibiotic ass. Diarrhoea
0.48 (95% CI 0.35 –
0.65)
• No statistically significant effect on:
o Traveller's diarrhoea
0.92 (95% CI 0.79 –
1.06)
o Community-based diarrhoea

177. Probiotics
A meta-analysis of data from RCTs,
Lactobacillus GG was associated with a
reduction in the duration of diarrhoea,
particularly of rotaviral etiology.
There is not enough evidence from
community-based studies, and from
developing countries to make any global
recommendation for use of probiotics in the
management of diarrhoea