KOLERA

Dr. dr. Shahrul Rahman, Sp.PD, FINA

Departemen Ilmu Penyakit Dalam

Fakultas Kedokteran
Universitas Muhammadiyah Sumatera Utara
Pendahuluan
penyakit diare akut (rice water diarrhea)
awal : V cholerae O1
akhir 1993 : V cholerae O139

Kolera Robert Koch (1884) : Vibrio Cholerae

Manifestasi klinis : dehidrasi renjatan

hipovolemik dan asidosis metabolik
dapat berakhir bila tidak ditang-
gulangi secara adekuat
 Emerging Infectious Disease
Mutation of organism to new serovar (antigenic
type)
Migration of humans and animals into new
environments
Travel
War and natural disasters
Decline in vaccination rates
Climatic changes
Cholera 1800s
Infant with Cholera
 First Cholera Pandemic

Why does an epidemic end?

Second Cholera Pandemic
Cholera
New York
1830s
 John Snow
John Snow is
credited by many
with developing
the modern field
of epidemiology
Epidemiologi
Kolera telah menyebar hampir ke seluruh dunia

Sulawesi (1961) menyebar melalui jalur Asia, Eropa, Afrika

dan Pasifik Selatan

Organisasi Kesehatan Pan-Amerika memperkirakan sampai Juni

1993 830.000 kasus kolera pada 20 negara belahan bumi
Barat 7200
Kemah pengungsi Rwanda (1994) 600.000 terinfeksi
V cholerae O1 45.000

Pada daerah endemi, kolera jarang dijumpai pada anak <1 tahun
 Cholera in the 1990s
Epidemic in Peru beginning 1991
From 1991-1994
Cases 1,041,422
Deaths 9,642 (0.9%)
Originated at coast, spread inland
World Cholera 2000-01
Gambar 1. Negara/daerah yg melaporkan kasus kolera pd thn 2004
Gambar 2. Negara/daerah yang melaporkan kasus kolera dan kasus-
kasus yang dilaporkan dari tahun 1995-2004
 Cholera and El Nio
Periodic warming of water near coast of
Central and South America
Large plankton blooms, especially in
coastal waters with nutrients from sewage
runoff
 Cholera and El Nio
Cholera in Bangladesh also seen to
fluctuate with El Nio, but with 11 month
lag
Rita Colwell and multinational group
studying link between climate and cholera
Satellite and surface data used to show
cholera incidence is related to sea surface
temperature
Cholera from Space
Cholera and Sea Surface
Temperature
 Cholera in the 1990s
Cholera O139 emerges in Asia
Different O (coat) antigen, 99% genetic
identity
O antigen is how human immune system
recognizes and protects against V. cholerae
More people susceptible
Etiologi

V cholerae kuman Gram negatif berukuran 0,2-0,4 m x 1,5-4,0 m,

batang-batang pendek sedikit bengkok (koma), tersusun berkelompok
seperti kawanan ikan yang berenang
 Microbe of the Day
Vibrio cholerae
Gram negative
curved rod
Toxin alters sodium
pump in intestinal
cells fluid loss
 Vibrio Cholera

Gram-negative
Curved rod
.5-.8 m width
1.4-2.6 m length
Facultative anaerobe
Single polar flagellum
Chemoorganotroph
Optimal growth 20-30 degrees
 Divisions of V. Cholera
o Biotype (biovar)
different strains of the same bacterial species
distinguished by a group of phenotypic or genetic traits
o Serogroup
bacteria of the same species with different antigenic
determinants on the cell surface

V. Cholera has more than 150 different serogroups, only two of

which cause epidemic disease
 Inaba
i pe
rot
se Ogawa
classic
t ipe
bio
V cholerae e Inaba
t ip
bio ro
ti se
pe Ogawa
El Tor

V cholerae O1 & O139 dapat menghasilkan enterotoksin

cholera toxin
 V. Cholera
01 serogroup

Classic
genome: 3.2-3.6 Mb
El Tor (El)
genome: 4 Mb

01 antigen is divided into 3

types: A,B,C
A antigen
made of 3-deoxy-L-
glycerotetronic acid
B, C antigen
not been characterized
 Horizontal Gene Transfer

1. acquisition of VPI
2. lysogenic conversion by phage
3. exchange of genes leads to expression of O-antigen and capsule
 V. Cholera

the 01 strain and the recent

0139 strain have different
antigens expressed in the
polysaccharide capsule

the change in structure is

thought to have arisen from
a recombination event.
 V. Cholera
two circular chromosomes

Chromosome 1 is larger (2.96

million base pairs) and carries
many genes for essential cell
functions and housekeeping

Chromosome 2 is smaller (about

1.07 million base pairs and
carries the integron island
 Cholera is not transmissible person-
to-person, but can easily be spread
through contaminated food and water
Water Supply London 1850s
Tabel 1. Species Vibrio yang menyebabkan penyakit pada manusia
Clinical Presentation
Species GI Wound/Ear Septicemia
V cholerae
V cholerae O1 ++ (+)
V cholerae O139 ++ (+)
V cholerae non-O1, non O139 ++ + (+)
V parahaemolyticus ++ + (+)
V pluvialis ++ ?
V mimicus ++ +
V hollisae ++ (+)
V furnissii ++
V vulnificus + ++ ++
V alginolyticus ? ++ ?
V damsela ++ ?
V cincinnatiensis +
V carchariae +
V metschnikovii ? ?
 Pathogenesis of V. Cholera

Cholera disease begins with ingestion of contaminated water or

food. The bacteria that survive the acidic conditions of the
stomach colonize in the small intestine.

The cholera toxin (CT) is responsible for the severe diarrhea

characteristic of the disease.

Cholera Toxin
CT is a proteinaceous enterotoxin secreted by
V. Cholera
 Incubation Period
Ranging from a few hours to 5 days
Most cases presenting within 1-3 days

As expected for organisms passing through the

gastric barrier, the incubation period is shortest
when:
highest dose of ingested organsim
High gastric pH
 Infectious Dose
Infectious dose ranges from 106 1011 colonizing
units
The high level is necessary as the bacteria must
survive the gastric acid barrier as the bacterium is
sensitive to acidic conditions
Additionally, V. cholerae must penetrate the mucus
lining the coats the intestinal epithelium, the
bacterium adheres to and colonizes the epithelial
cells of the small intestine.
 John Snows Observations
People with cholera developed immediate
digestive problems: cramps, vomiting,
diarrhea
Face, feet, hands shriveled and turned blue;
died in less than a day
Probably spread by vomiting and diarrhea
Gejala Klinis
Masa inkubasi ( 45 jam) kolera dimulai dengan diare yg encer
dan berlimpah, tanpa mulas dan tenesmus

Feses pd pasien kolera : warna abu-abu, sedikit keruh, tdk berdarah,

manis, bau tidak menyengat

Muntah timbul setelah diare dan berlangsung tanpa mual

Gangguan elektrolit dapat bermanifestasi sebagai kelemahan

otot, ileus atau aritmia jantung
Jumlah cairan diare
dpt mencapai 500-1000
cc/jam
Takikardi, hipotensi, kolaps vaskular,
lidah menjadi kering, mata menjadi
cekung, produksi urine jauh berkurang
dehidrasi sampai berhenti, turgor kulit , jari
keriput, suara serak, somnolen sampai
koma
Tanda & Gejala :
Masa inkubasi : 24 -48 jam.
- Diare cair dan banyak(bisa > 250 ml / kgBB).
- Warna tinja spt cucian beras
- Tanpa rasa sakit dan demam.
- Muntah.
- Haus, lemah
- Kramp otot ok kekurangan elektrolit.
- Kesadaran menurun ok hiponatremia & dehidrasi.
- Pernafasan Kussmaul ok asidosis metabolik ok
kekurangan bikarbonat.
- Hipotensi postural, nadi lemah,
- Turgor jelek, oliguria
- Woman washer hand/washer woman.
- Dehidrasi --- syok hipovolemik --- kematian.
 Symptoms
Diarrhea may be sudden
or gradual Abdominal cramping
Rapid onset of water
associated with stool
** Fever is infrequent since
Vomiting, frequently
cholera is not invasive infection
watery, is common and
may begin before or
after diarrhea.
 Severe Disease
Cholera Gravis
Notable for how quickly healthy person becomes ill
Patients present after a few hours with massive
volume loss
500 1000 ml per hour, can rapidly lose more than
10% of their body weight
Mortality
Circulatory collapse from dehydrating effects of the
pathogen
 Cholera Gravis

Severest form of cholera

Infection in 2% of infected individuals
Patients with blood type O most susceptible
Characterized by voluminous expulsion of
electrolyte-rich fluid in patients stool
Amounts greater or equal to patients blood volume
Responds well to rehydration therapies
In areas where not available, death rates are
astronomical
 Complications: Severe Disease
Complications result from massive volume and electrolyte
loss as the Cholera stool contains high concentrations of
sodium, potassium, chloride, and bicarbonate

Therefore in addition to volume depletion, which can

cause renal failure, additional complications can occur:
Hypokalemia: causes arrhythmias, ileus, leg cramps
Metabolic Acidosis: due to phosphate moving out of cells
Hypoglycemia: mental status changes and seizures
Hypotension: due to water loss
Hypofusion of critical organs
 Mortality
In untreated patients, mortality can reach 50-70%
Risk much higher in children
10x greater than adults
As well as pregnant women
50% risk of fetal death in 3rd trimester
Patients can die within 2-3 hours of first sign of
illness also seen from 10 hours- several days
Laboratorium
Ht , lekositosis ringan, ureum dan creatinin , bikarbonat
dan pe an anion gap
pH arteri biasanya rendah

Feses dikultur pada media TCBS (thiosulfate-citrate-bile salt-

sucrose)
Metode ELISA, agglutinasi lateks dan PCR mendeteksi kolera

Diagnosis
Diagnosis kolera berat tidak sukar
Kolera yg khas dapat dikenal : diare yg sering tanpa mulas diikuti
muntah tanpa mual, cairan tinja spt air cucian beras, suhu yg tetap
normal atau turun dan keadaan pasien cepat bertambah buruk
 Diagnosis
Cholera should be considered in all cases with
severe watery diarrhea and vomiting
However, there are no clinical manifestations that
can distinguish cholera from other infectious
causes of severe diarrhea
Differential Diagnosis include:
Enterotoxigenic e. Coli
Bacterial food poisoning
Viral gastroenteritis
 Visible Symptoms

These include:
Sunken eyes and cheeks
Decreased skin suppleness
Dry mucous membranes
Urine production is sharply
decreased or stopped altogether
Renal failure is the most common
complication seen in recent outbreaks
 Diagnosis continued
Dehydrating diarrhea may be more common in
children but adults should be questioned as to
recent trips to Africa, Asia and central America
Additional questions asked about ingestion of
undercooked or raw shellfish
 Laboratory Diagnosis
Made through isolation of bacteria from extra-
intestinal environment or stool samples
Specimens are collected
Gram Stain show sheets of curved Gram negative rods
Untreated patients have 106 to 108 organisms / mL
Important to start treatment before the cause of
infection is identified: death can occur within
hours
 Laboratory Diagnosis Cont.

Vibrios often detected by dark field or phase

contrast microscopy of stool
Organisms are motile, appearing like shooting
stars
When plated on sucrose dishes, yellow colonies
appear confirming cholera present
Additional methods of detection include PCR and
monoclonal antibody-based stool tests.
 Tatalaksana

Langkah-langkah dalam tatalaksana penderita suspek kolera :

Langkah 1 : Menilai derajat dehidrasi

Langkah 2 : Memberikan cairan rehidrasi dan mengawasi penderita
secara ketat, kemudian menilai kembali derajat dehidrasinya
Langkah 3 : Mempertahankan hidrasi dengan cara mengganti cairan yg
hilang saat itu sampai diarenya berhenti
Langkah 4 : Memberikan antibiotika oral kpd penderita dehidrasi berat

Langkah 5 : Memberikan makanan kepada penderita

Langkah 1 : Menilai derajat dehidrasi

Tabel 2. Penilaian dehidrasi penderita diare

Tanda-tanda vital Tanpa dehidrasi- Dehidrasi sedang Dehidrasi berat

dehidrasi ringan

Kesadaran Normal Gelisah, rewel* lesu,lunglai-

somnolen*
Nadi Normal cepat dan lemah halus-tdk teraba
Tekanan Darah Normal TDS dpt menurun TDS 60 mmHg
tapi >60 mmHg
Respirasi Normal Normal cepat & dalam
(Kussmaul)
Suhu Normal Normal Normal -
hypotermia
Perhatikan Tanpa dehidrasi- Dehidrasi sedang Dehidrasi berat
dehidrasi ringan

Rasa haus Minum baik Haus, ingin minum* Tdk bisa minum*
tdk haus
Mata Normal cekung sgt cekung&kering
Wajah Normal pipi cekung pipi cekung, tlg
pipi menonjol
(Facies Cholerica)
Bibir, mulut Basah Kering Bibir kebiruan,
dan lidah sgt kering
Suara Normal Normal Parau (Vox
Cholerica)
Kulit jari tangan Normal Keriput Sgt keriput (Washer
dan kaki Woman Hands)
Bentuk perut Normal Normal Cekung
Auskultasi Peristaltik usus normal Peristaltik usus Bunyi jtg jauh,
normal Peristaltik usus
Turgor kulit Kulit normal, Kulit normal, Dingin & lembab,
Kembali cepat Kembali lambat* Kembali sgt
lambat*
Jumlah urine Normal Normal-oliguria Oliguria-anuria
 Cara membaca tabel :
- Baca tabel dari kolom kanan ke kiri
- Kesimpulan derajat dehidrasi penderita ditentukan dari adanya satu
gejala kunci (yg diberi tanda bintang) ditambah minimal satu gejala
lain pada kolom yang sama

Langkah 2 : Memberikan cairan rehidrasi dan mengawasi penderita

secara ketat, kemudian menilai kembali derajat dehidrasinya

Dehidrasi berat cairan iv sesegera mungkin (jumlah cairan yang

diberi dapat dihitung menurut skor Daldiyono atau dengan meng-
hitung berat jenis plasma)
Tabel 3. Skor Daldiyono
Gejala klinis Skor
Muntah 1
Vox cholerae 2
Apatis 1
Somnolen,sopor,koma 2
Sistole 90 mmHg 2
Nadi 120x/menit 1
Pernafasan Kussmaul (<30 x/i) 1
Turgor kulit kurang 1
Facies Cholerica 2
Ekstremitas dingin 1
Washer hand 1
Sianosis 2
Umur 50 tahun -1
Umur 60 tahun -2

Jumlah cairan yang diberikan dalam 2 jam :

Score/15 x 10% x BB (kg) x 1 liter
Dengan memakai berat jenis plasma, dengan
rumus :
BD Plasma 1,025 x Berat badan (Kg) x 4 ml
0,001
Oralit diberi setelah penderita dapat minum

dehidrasi berat : ulangi pemberian cairan iv

Setelah 3 jam dehidrasi ringan sedang : ikuti tatalaksana utk
nilai kembali dehidrasi ringan -sedang

tidak ada dehidrasi : lanjut ke langkah 3

Dehidrasi sedang cairan iv + oralit

Dehidrasi ringan oralit ad libitum
 Perkiraan jumlah oralit yang diberikan pada 3 jam pertama
Oralit yang diberikan dihitung dengan mengalikan
Berat badan penderita (kg) dengan 75 ml
Atau untuk memudahkan, maka untuk
dewasa dapat diberikan 2400 ml

Awasi penderita dengan ketat untuk memastikan bahwa cairan oralit

diminum dengan baik
dehidrasi (+) : ulangi tatalaksana diatas
Nilai kembali
setelah 3 jam dehidrasi (-) : lanjut ke langkah 3
Tanpa dehidrasi dapat diobati di rumah dengan memberikan
oralit cukup untuk 2 hari

Umur Jlh oralit yg diberi Jlh oralit yg disediakan

tiap BAB di rumah
< 12 bulan 50-100 ml 400 ml/hari (2 bungkus)
1-4 tahun 100-200 ml 600-800 ml/hari
(3-4 bungkus)
> 5 tahun 200-300 ml 800-1000 ml/hari
(3-4 bungkus)
Dewasa 300-400 ml 1200-2800 ml/hari
(6-12 bungkus)
Mintalah penderita untuk kembali bila timbul gejala-gejala :
- Frekuensi BAB
- Tidak mau makan dan minum
- Rasa haus yang nyata
- Muntah yang berulang
atau timbul :
- Panas
- Adanya darah dalam tinja
 Oral Rehydration
Oral Rehydration Solutions (ORS) have reduced
mortality from cholera from over 50% to less than
1%.
ORS utilizes the fact that sodium and water
absorption in the small intestine is facilitated by
glucose and occurs in the presence of cholera toxin
Used when the dehydration is less than 10% of
body weight
 O.R.S.
The World Health Organization recommends a
solution containing:
3.5 g sodium chloride
2.9 g trisodium citrate/ sodium
bicarbonate
1.5 g potassium chloride
20 g glucose or 40 g sucrose
Per liter of water
Min. of 1.5 x the stool volume losses should be
administered
Commercially sold over-the-counter as
rehydralyte
ORS
 Intravenous Rehydration

Used in patients who lost more than 10% of body

weight from dehydration or are unable to drink
due to vomiting
Ringers Lactate used commercially in hospitals
with appropriate electrolyte concentrations
specified to patients needs
 Intravenous Rehydration
Additional Options

Saline can be used, however, bicarbonate and

potassium losses are not being replaced
Glucose in water; this does not replace the
sodium, bicarbonate, or potassium losses

Dosage =
Langkah 3 : Mempertahankan hidrasi dengan cara mengganti cairan yg
hilang saat itu sampai diarenya berhenti
Penderita yang sudah terrehidrasi dan dehidrasi (-) Oralit tetap
diberi dengan tujuan mengganti cairan tinja yang keluar

Jumlah cairan oralit yang dibutuhkan untuk mempertahankan hidrasi

tergantung dari volume tinja yang keluar

Dalam 24 jam pertama, kebutuhan setiap penderita 200 ml/kg BB

tapi bisa 350 ml/kg BB dengan memperhitungkan jumlah cairan
yang keluar

Tanda-tanda dehidrasi dinilai kembali setiap 3-4 jam bila dijumpai

tanda-tanda dehidrasi kembali ke langkah 2
 Penderita harus selalu diawasi, bila mungkin, sampai diare berhenti
atau jarang dan jumlahnya sedikit

Bila penderita harus dipulangkan sebelum diare berhenti, ajarkan

cara menyiapkan dan memberikan larutan oralit

Langkah 4 : Memberikan antibiotika oral kpd penderita dehidrasi berat

Antibiotika yang efektif dapat mengurangi volume diare

Antibiotika diberi pada penderita dehidrasi berat dan berumur

lebih dari dua tahun

Pemberian antibiotika dimulai setelah penderita terrehidrasi dan

setelah berhenti muntah
 Tabel 5. Antibiotika yang digunakan dalam pengobatan kolera

Antibiotika Anak-anak Dewasa

Lini Pertama

Doxicycline (Dosis tunggal) 200 mg

Tetracycline 4x500 mg selama 3 hari

Lini Kedua

Trimetothoprim (TMP)
TMP 5 mg/kg BB & TMP 160 mg
Sulfamethoxazole (SMX)
SMX 25 mg/kg SMX 800 mg
2 x sehari selama 3 hari

Ciprofloxacin (Dosis tunggal) 1000 mg

Azithromycin (Dosis tunggal) 1000 mg
 Dosage Antibiotic Agents

Given orally when vomiting

stops.
Tetracycline is the standard
treatment
Administered in single dose
primarily to prevent spread
of secondary infection

WHO guidelines
Cholera Antibiotic Resistance
Cholera is
becoming
resistant to
several
antibiotics
 Tetracycline Resistance
Many strains of V. Cholerae now harbor plasmids
carrying multiple antibiotic resistances.
Fluoroquinolones are now an effective alternative
in regions where tetracycline resistance is
common

Langkah 5 : Memberikan makanan kepada penderita

Tidak ada pembatasan diet pada penderita kolera dewasa
 Prevention
V. Cholerae is spread through contaminated food
and water, therefore, prevention depends upon the
interruption of fecal-oral transmission
Anti-biotic prophylaxis, vaccines and surveillance
of new cases are the answer to preventing the
spread of disease.
Sari Cloth Filtration:
Preventative Measure

Using Sari cloth to filter

Water
 Antibiotic prophylaxis
The World Health Organization recommends
prophylaxis if 1 household member in a family
becomes ill.
Mass administration of antibiotics to a whole
community is not effective nor recommended
 Vaccines
Two types of cholera vaccines are currently
approved for use in humans.
Killed-whole-cell formulation: killed bacterial cells
from both biovars of serovar 01 and purified B subunit
of the cholera toxin.
Provides immunity to only 50% of adult victims and to
less than 25% of child victims.
Live-attenuated vaccine, genetically engineered
Provides >90% protection against classical biovar and 65-
80% agaisnt E1Tor biovar.
 Vaccines: Problems
The live vaccine is associated with certain
problems:
Side Effects:
Cause mild diarrhea, abdominal cramping and slight fever
Possible virulence of live strain
Upon infection of the vaccine strain by cholera toxin
Vaksin Kolera
Penggunaan vaksin kolera merupakan alat pelayanan kesehatan
tambahan untuk pencegahan kolera selain persediaan air yg bersih
dan sanitasi yang adekuat
Penggunaan vaksin kolera oral direkomendasikan pada populasi
untuk membatasi resiko dari :
- terjadinya wabah kolera pd populasi yang akan meninggalkan
area yang endemi kolera
- penyebaran dan insiden kolera selama wabah
 Vaksin kolera oral ada 2 jenis, yaitu :

1. Vaksin kolera dosis tunggal efek protektif didapat 8 hari setelah

vaksin diberikan dapat diberikan ketika wabah terjadi

2. Vaksin kolera dua dosis efek protektif didapat 10 hari setelah

dosis kedua tidak diindikasikan ketika wabah telah terjadi

Kedua jenis vaksin ini tidak dapat melindungi dari Vibrio cholerae
O139