Ida Safitri Laksono
Number of Typhoid fever cases yearly 275639 255817 201252 134065
136088
2000
2001
2002
2003
2004
Incidence rate per 10.000 people of Typhoid fever cases yearly 13 12 9.5
Subdit Surveillance Epd Ministry of Health
6.2
6.4
2000
2001
2002
2003
2004
Bulletin WHO 2008
Host barriers Local : pH, GIT motility , intestinal flora General :
humoral and sellular immunity
Organism Number of microbes Virulence (serotype)
Antibiotic resistance
Intestinal Epithel Lamina propria Multiplication
Plaque Payeri
phagocytocis Inflamation response endotoxin (local, systemic) Local: inflamation Systemic: cytokine
Thoracic Duct Primary bakteremia
circulation Target Organ RES (Liver, spleen, bone marrow)
Secundary bakteremia Other organs (metastatic)
Incubation period Asimptomatic
Invasive period
Typhoid phase
Convalescence
Intermittent fever Headache Malaise Abdominal pain Constipation Diarrhea
Persistent fever Bradicardia Hepatomegaly Splenomegaly Constipation Diarrhea Rose spot
Carrier Relapse
Complication 370C
Day -15
400C
Day 0
Fever
Day 7
Day 21
Not specific symptoms and signs Fever ≥ 7 days Gastrointestinal symptoms Vomiting, Diarrhea / obstipation, Meteorismus
Delirium, decreasing consciousness Adolescent ~ adult Toxic appearance, dehidrated, Typhoid tongue hepatomegaly, splenomegaly
Sri Rezeki H, Tumbelaka AR, Satari HI. Sari Pediatri 2001;4:182-7
Fever Chilling Abdominal pain Nausea Vomiting Diarrhea Obstipation Raving Unconsciousness Typhoid tongue Epigastric pain Hepatomegaly Splenomegaly 10
25
50
75
100
Laboratory scheme of typhoid fever
Blood counts leucopenia, aneosinophilia, relative lymphocytosis thrombocytopenia
Increasing BSR, Increasing SGOT/SGPT Serological test : IgM & IgG Culture of Salmonella typhi
Serological test : Widal test, Tubex – TF, etc DNA probe IgG of outer cells membrane Immunoblotting (Typhi‐dot) PCR (polymerase chain reaction)
Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ 2006;333:78‐82.
Widal test, since 1896 O antibody, established earlier but for short time only (4 ‐ 6 months), H antibody, later and stay longer (9 months – 2 years), Vi antibody, late (persist in carriers)
Interpretation of Widal test should be taken carefully, depend on : Disease stadium Laboratory methods Endemicity of disease Immunisation history Nsutebu EF, Ndumbe PM, Koulla S. Trans R Soc Trop Med Hyg. 2002 Jan-Feb;96(1):64-7.
Advantages of Widal test Olopoenia LA, King, AL. Widal agglutination test - 100 years later: still plagued by controversy. Postgrad Med J 2000;76:80-84.
GROUP
SEROTYPE
ANTIGEN O
ANTIGEN H PHASE I
PHASE II
A
S. paratyphi A
1, 2, 12
a
-
B
S. paratyphi B
1, 4, 5, 12
b
1,2
S. typhimurium
1, 4, 5, 12
i
1,2
S. paratyphi C
6, 7
c
1,5
S. Cholerasuis
6, 7
c
1,5
S. typhi
9, 12, Vi
d
-
S. enteritidis
1, 9, 12
g, m
C D
Out of 103 patients (clinical and cultural proven typhoid), TUBEX pos in 86.4%, Typhidot 74.7%, and Widal 69.9% In non typhoid group, Tubex pos in 25%, Typhidot 3.8% and Widal 26,9% Maximum number of Tubex and Typhidot were positive in patients with 7 – 14 days of fever, while Widal was mostly positive in children with fever of more than 14 days Sensitivity, specificity, PPV and NPV for the tests
Tubex
86.4
84.6
95.7
61.1
Typhidot
74.7
96.1
98.7
49.0
Widal
69.9
73.0
91.1
38.0
Jaffery G, Hussain W, Saeed, Anwer M and Maqbool S. Annual Pathology Conference, 2003, Pakistan and 3rd Scientific Conference of Paediatric Association of SAARC Countries 2004, Lahore
Tubex TF dibandingkan dengan Uji Widal pada pasien dengan biakan darah dan/atau PCR
RSCM, RS Persahabatan, RS Tangerang , Mei – Oktober 2006 Diperiksa 52 kasus, 27 laki2 dan 25 wanita dengan usia tertua 20 – 30 tahun (53.8 %) Semua pasien telah memenuhi Skor tifoid Nelwan > = 8 dan klinis memenuhi syarat demam tifoid. Tubex TF dibanding uji Widal terhadap skor itu menghasilkan Sensitifitas 100% dan 53.1% Spesifitas 90% dan 65% Nilai prediksi positif 94.1% dan 70.8%, prediksi negatif 100% dan 46.4% Ratio likelihood (+) 10 dan 1.51, Ratio likelihood (‐) 0 dan 0.72 AUC ROC Tubex 5.91 dan Widal 0.591, sangat berbeda bermakna Surya H, Setiawan B, Shatri H, Sudoyo A dan Loho T. Diunduh dari http:/pacbiotekindo.co.id/tubextf.html, 29.11.2009
Intra intestinal tract
▪ peritonitis, ▪ bleeding, ▪ perforation
Outside intestinal tract
▪ encephalitis ▪ pneumonia ▪ meningitis ▪ osteomyelitis ▪ hepatitis
One third of 102 cases develop complications Anicteric hepatitis, bone marrow supression, paralytic ileus,
myocarditis, psychosis, cholesystitis, osteomyelitis, peritonitis, pneumonia, hemolysis, and SIADH If hepatitis is excluded, the rate of complications is 11 %.
A child with splenomegaly or thrombocytopenia had 1.5 times higher risk, where as a child with leucopenia has 2 times risk to have complications. A child with both splenomegaly and thrombocytopenia or leukopenia had 2.5 times higher risk. Alam Sher Malik. J of Trop Ped 2002;48:102-8.
Irritability Decreasing consciousness (late stadium) Abdominal distension Abdominal pain Defanse musculaire Lowering intestinal sounds Disappearance of hepatic dullness
Clinically difficult to differentiate Need supportive labs Nasogastric and anal tube should be inserted Abdominal x‐ray (3 positions) Unequal air distribution Air fluid level Hepatic area radio lucent Free air at abdominal wall
Supportive : Fluid therapy, dietetic Electrolyte Acid base
Causal : Medicamentous (antibiotics, steroid) Surgery (complication therapy)
Fluid Maintenance, D5 : NaCl 0.9% (3:1) Additional 12.5% for each 10 C increment
Dietetic Solid foods could be given as soon as possible, instead of
conventional strained food Less fibers and stimulating food Not to strict
Acid base corrections Electrolyte corrections
Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ 2006;333:78‐82.
Antibiotics
Sensitive
Interme diate
Resistant
Ampicillin
34
10
54
Amoxycillin
28
6
66
Nalidixic acid
64
12
24
Chloramphenicol
46
40
24
Cefixime
80
14
6
Azithromycine
78
22
0
Cotrimoxazole
64
0
36
Ciprofloxacin
84
1
15
E Hartoyo, A Yunanto, L Budiarti. 3rd Congress of Pediatric Infectious Diseases. Cebu City, Philippines, March 2006
Chloramphenicol 100mg/kgBW/day oral, max 2 gram, 10 days Not recommended for cases with leucocyte count <2000/Ul
Cotrimoxazole 6mg/kgBW/day, 10 days
Amoxicillin 100 mg/kgBW/day, 10 days
Ceftriaxone (cephalosporin 3rd gen) 50 ‐ 80 mg/kgBW/day , 5 days
Cefixime (cephalosporin 3rd gen) 10 ‐ 20 mg/kgBW/day , 10 days Oral
Azithromycin 20 mg/kg/day
Fluoroquinolone Not recommended for <14 years old
RCT comparing Ceftriaxone 75 mg/BW flexible duration to Chloramphenicol 75 mg/BW 14 days give mean defervescence of 5.4 days and 4.2 days respectively. No relaps in Ceftriaxone groups, but 4 cases in Chloramphenicol. Tatli MM, Aktas G, Kosecik M, Yilmaz A. Int J Antimicrobial Agents 2003;21:350-3
Ceftriaxone 50 mg/BW once a day for 14 days, give mean defervescence of 5.31 days and conciousness improving the first 4 hour in all cases except 2. Nathin MA, Hadinegoro SR. In RHH Nelwan, editor. Typhoid fever, profile, diagnosis and treatment in the 1990’s. FKUI Press, Jakarta, 1992:133-9
From 24 isolates, 87% of them sensitive to ampicillin, 96% to chloramphenicol and cotrimoxazole. All isolates were sensitive to Cefixime. Since fluoroquinolone is not recommended for children, cefixime could play a role as a choice in endemic areas with MDRST Santillan RM, Garcia GR, Benavente IS, and Garcia. Proc West Pharmacol Soc 2000;43:65-6
In FMUI‐CHD Jakarta, from 25 cases confirmed typhoid fever, cefixime 10‐15 mg/BW give 84% cure rate, with a mean defervescence time of 6.0 ± 3.1 days. Hadinegoro SR, Tumbelaka AR, Satari HI. Sari Pediatri 2001;2(4): 182-7
Asitromisin Pada 149 kasus anak dan remaja, yang menderita demam tifoid klinis diberikan asitromisin oral (20 mg/kg/hari) atau seftriakson iv (75 mg/kg/hari) selama 5 hari. Ternyata 30 (94%) kelompok asitromisin serta 35 (97%) dari kelompok seftriakson sembuh dan tidak berbeda bermakna. Enam kasus dengan seftriakson mengalami relaps dan tidak ada relaps pada kelompok asitromisin. Pengobatan 5 hari dengan asitromisin dinyatakan cukup efektif untuk mengobati demam tifoid tanpa komplikasi pada anak dan remaja.
Frenck RW, Mansour A, Nakhla I, Sultan Y, Putnam S, Wiezerba T et al. Clin Infect Dis. 2004;38(7):951-7.
Fever defervescence (days) Ampicilin/Amoxicilin Cotrimoxazole Chloramphenicol Ceftriaxone Cefixime
5,2 ± 3,2 6,5 ± 1,3 4,2 ± 1,1 5,4 ± 1,5 5,7 ± 2,1
Hadinegoro SR. Naskah lengkap PKB Ilmu Kesehatan Anak XLIV. Jakarta: FKUI 2001 :105-16.
Encephalopaty Dexametason 1‐3 mg/ BW/day, 3‐5 days Fluid restriction to 4/5 Acid‐base and electrolyte correction
Peritonitis, intestinal hemorrhage Fasting, parenteral nutrition, blood transfusion (if
indicated) parenteral antibiotic
Hospital
RSCM RSHS RSWS RSK RSMH
Mortality (%) 0 ‐ 0 ‐ 0 ‐ 0 ‐ 0 ‐
4,0 0,6 3,3 2,0 3,2
RSCM Jakarta, RSHS Bandung, RSWS Makasar, RSK Semarang, RSMH Palembang, 1991‐1996
Typhoid fever in children, mostly > 5 years of age Clinically milder than adult cases, Clinically not specific in younger children Sensitivity, specificity, and low cost laboratory support needed Drug of choice : chloramphenicol Prevention: vaccine and good hygiene sanitation
