Enteric (Typhoid) Fever

Definition

 Is a systemic disease characterized by fever and abdominal pain

and caused by dissemination of S. typhi or S. Paratyphi.
 Initially called typhoid fever because of its clinically similarity to
typhus
 1800s – defined pathologically as a unique illness on the basis of its
association with enlarged Peyer’s patches and mesenteric LN
 1869 – given the anatomic site of infection, the term enteric fever
was proposed as an alternative designation to distinguish typhoid
fever from typhus.
Epidemiology

 Worldwide, there are an estimated 27 million cases of enteric fever,

with 200,000 – 600,000 deaths annually. The annual incidence is
highest (>100 cases/100,000 population) in south central and
Southeast Asia. 1
Etiology
Genus G(-) bacilli
within
Enterobacteriaceae
family

Salmonella are G(-),

Non-spore forming,
facultatively anaerobic
Salmonella enterica, bacilli that measure 2-3
which contains 6 Salmonella bongori
subspecies µm by 0,4-0,6 µm.

Subsepcies I – almost
all the serotypes
pathogenic for
humans
 Pathogenesis

Once
phagocytosed,
Once reach the
typhoidal
small intestine, they
salmonellae
penetrate mucus
After crossing disseminate
Ingestion of organism layer of the gut and
epithelial layer of the throughout the body
(contaminated food traverse the intestinal
SI they are in macrophages via
or water), 200 CFU to layer through
phagocytosed by the lymphatics and
106 phagocytic
macrophages. colonize
microfold (M) cells)
reticuloendothelial
that reside within
tissues (liver, spleen,
Peyer’s patches
LN, and bone
marrow)
Clinical Course

 The incubation period for S. typhi averages 10–14 days but ranges
from 5 to 21 days, depending on the inoculum size and the host’s
health and immune status.
 The most prominent symptom is prolonged fever (38.8–40.5 C; 101.8
–104.9 F), which can continue for up to 4 weeks if untreated
 Early physical findings of enteric fever include rash (“rose spots”;
30%), hepatosplenomegaly (3–6%), epistaxis, and relative
bradycardia at the peak of high fever (<50%). 1 Rose spots
commonly appears during the second week of disease. Disappears
in 3-4 days.
 “Rose spots” the rash of enteric fever due to
Salmonella typhi or Salmonella paratyphi

Rose spots make up a faint, salmon-colored, blanching, maculopapular rash located primarily
on the trunk and chest
Clinical Findings

 During the prodromal stage,

 there is increasing malaise, headache, cough, and sore throat, often
with abdominal pain and constipation
 While the fever ascends in a stepwise fashion, after about 7-10 days,
it reaches plateu and the patient Is much more ill, appearing
exhousted and often prostrated.
 There may be marked constipation, especially early, or “pea soup:
diarrhea; marked abdominal distention occurs as well.
 If there are no complications, the patient’s condition will gradually
improve over 7-10 days. However, relapse may occur for up to 2
weeks after defervescence.
Clinical Findings

 Gejala yang biasanya dijumpai

 adalah demam sore hari dengan serangkaian keluhan klinis, seperti
anoreksia, mialgia, nyeri abdomen, dan obstipasi.
 Dapat disertai dengan lidah kotor, nyeri tekan perut, dan
pembengkakan pada stadium lebih lanjut dari hati atau limpa atau
kedua-duanya
 Pada anak, diare sering dijumpai pada awal gejala yang baru, kemudi-
an dilanjutkan dengan konstipasi.2 Konstipasi pada permulaan sering
dijumpai pada orang dewasa.
 Pada sekitar 25% dari kasus, ruam makular atau makulo- papular (rose
spots) mulai terlihat pada hari ke 7-10, terutama pada orang berkulit
putih, dan terlihat pada dada bagian bawah dan abdo- men pada
hari ke 10-15 serta menetap selama 2-3 hari.

“Tatalaksana Terkini Demam Tifoid” CDK-192/ vol. 39 no. 4, th. 2012

Demam Tifoid pada Anak
 DemamTifoid
 Pertimbangkan demam tifoid jika anak demam dan mempunyai salah
satu tanda berikut ini: diare atau konstipasi, muntah, nyeri perut, sakit
kepala atau batuk, terutama jika demam telah berlangsung selama 7
hari atau lebih dan diagnosis lain sudah disisihkan.
 Diagnosis
 Pada pemeriksaan, gambaran diagnosis kunci adalah:
 Demam lebih dari tujuh hari
Terlihat jelas sakit dan kondisi serius tanpa sebab yang jelas
Nyeri perut, kembung, mual, muntah, diare, konstipasi
Delirium
Hepatosplenomegali
Pada demam tifoid berat dapat dijumpai penurunan kesadaran,
kejang, dan ikterus
Dapat timbul dengan tanda yang tidak tipikal terutama pada bayi
muda sebagai penyakit demam akut dengan disertai syok dan
hipotermi.
Demam Tifoid pada Anak

 Pemeriksaan penunjang
 Darah tepi: leukopeni, aneosinofilia, limfositosis relatif, trombositopenia
(pada demam tifoid berat).
Serologi: interpretasi harus dilakukan dengan hati-hati.
 Tatalaksana
 Obati dengan kloramfenikol (50-100 mg/kgBB/hari dibagi dalam 4 dosis
per oral atau intravena) selama 10-14 hari
Jika tidak dapat diberikan kloramfenikol, dipakai amoksisilin 100
mg/kgBB/ hari peroral atau ampisilin intravena selama 10 hari, atau
kotrimoksazol 48 mg/kgBB/hari (dibagi 2 dosis) peroral selama 10 hari.
 Bila klinis tidak ada perbaikan digunakan generasi ketiga
sefalosporin seperti seftriakson (80 mg/kg IM atau IV, sekali sehari,
selama 5-7 hari) atau sefiksim oral (20 mg/kgBB/hari dibagi 2 dosis
selama 10 hari).
Diagnosis

 Diagnosis needs to be considered in any febrile traveler returning

from a developing region, especially the Indian subcontinent, the
Philippines, or Latin America.
 Positive Culture
 In 15-25% of cases, leukopenia and neutropenia are detectable.
 Leukocytosis is more common among children, during the first 10
days of illness,
 Definitive diagnosis of enteric fever requires the isolation of S. typhi
or S. paratyphi from blood, bone marrow, other sterile sites, rose
spots, stool, or intestinal secretions.
Diagnosis

Blood culture 40-80 % sensitive

Bone marrow culture 55-90 % sensitive, its yield is not
reduced by up to 5 days of prior
antibiotic therapy
Stool cultures Although negative in 60-70% of cases
during the first week, can become
postive during the third week of
infection in untreated patients

• Serologic tests, including the classic Widal test for “febrile agglutinins” and
rapid tests to detect antibodies to outer membrane proteins or O:9 antigen
have lower positive predictive values than blood culture.
Widal vs Typhidot
 Sensitivity Specificity

TPTest 96 % 96,6 %

Tubex 60,2 % 89,9 %

Typhidot 49,3 % 80 %
Treatment

For treatment of drug-

susceptible typhoid fever,
fluoroquinolones are the
most effective class of
agents, with cure rates of
~98% and relapse and
fecal carriage rates of
<2%.
Treatment

 Patients with persistent vomiting, diarrhea, and/or abdominal

distension should be hospitalized and given supportive therapy as
well as a parenteral third-generation cephalosporin or
fluoroquinolone, depending on the susceptibility profile.
 Therapy should be administered for at least 10 days or for 5 days
after fever resolution.
 In a randomized, prospective, double-blind study of critically ill
patients with enteric fever (i.e., those with shock and obtundation)
in Indonesia in the early 1980s, the administration of dexamethasone
(an initial dose of 3 mg/kg followed by eight doses of 1 mg/kg every
6 h) with chloramphenicol was associated with a substantially lower
mortality rate than was treatment with chloramphenicol alone
Treatment for Carriers

 Ciprofloxacin, 750 mg orally twice a day for 4 weeks, has proved to

be highly effective in eradicating the carrier state.
 Cholecystectomy may also achieve this goal.
Pendidikan Kedokteran Berkelanjutan “Update Management of Infectious Diseases and
Gastrointestinal Disorders” 2012, DEPARTEMEN ILMU KESEHATAN ANAK FKUI
Complications

 Komplikasi yang sering dijumpai adalah,

 Reaktif hepatitis,
 Perdarahan gastrointestinal
 Perforasi usus
 Ensefalopati tifosa, serta gangguan pada sistem tubuh lainnya
mengingat penyebaran kuman adalah secara hematogen.

“Tatalaksana Terkini Demam Tifoid” CDK-192/ vol. 39 no. 4, th. 2012

 Neurological manifestations were diagnosed in 27.1% (n = 68) of the
above 232 patients. Patients with neurological manifestations were
broadly categorised into two groups:
 Typhoid delirium state or typhoid toxaemia : 42.8% (n = 27).
 Specific neurological complications : 57.2% (n = 36).
 Encephalitic disorders in 25% (n = 9) as the commonest,
 Psychiatric disorders, and cerebellar ataxia in 19.44% (n = 7) of patients each.
 Other prominent manifestations included
 Meningitis (13.89%; n = 5);
 Polyneuropathy (8.33%; n = 3); and
 Extra- pyramidal syndromes (5.56%; n = 2)
Prevention

 Penyediaan makanan dan minuman yang tidak terkontaminasi,

higiene perorangan terutama menyangkut kebersihan tangan dan
lingkungan, sanitasi yang baik, dan tersedianya air bersih sehari-hari
Prevention

Vaksinasi
 Vaksin Vi Polysaccharide
Vaksin ini diberikan pada anak dengan usia di atas 2 tahun dengan
dinjeksikan secara subkutan atau intramuskuler. Vaksin ini efektif selama
3 tahun dan direko- mendasikan untuk revaksinasi setiap 3 tahun.
Vaksin ini memberikan e kasi perlindungan sebesar 70-80%.
 Vaksin Ty21a
Vaksin oral ini tersedia dalam sediaan salut enterik dan cair yang
diberikan pada anak usia 6 tahun ke atas. Vaksin diberikan 3 dosis yang
masing-masing diselang 2 hari. Antibiotik dihindari 7 hari sebelum dan
sesudah vaksinasi. Vaksin ini efektif selama 3 tahun dan memberikan e
kasi perlindungan 67-82%.
 Vaksin Vi-conjugate
Vaksin ini diberikan pada anak usia 2-5 tahun di Vietnam dan
memberikan e kasi perlindungan 91,1% selama 27 bulan setelah
vaksinasi.
Prognosis

 The mortality rate of typhoid fever is about 2% in treated cases.

Elderly or debilitated persons are likely to do worse.
 Relapses occur in up to 15% of cases.
Sources

1. Harrisons’ Principles of Internal Medicine 19th edition

2. Current Medical Diagnosis and Treatment, 2018
3. “Tatalaksana Terkini Demam Tifoid” CDK-192/ vol. 39 no. 4, th. 2012