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Diagnosis, Treatment and Prevention of Typhoid Fever in the Children of
Bangladesh: A Microbiologist’s View.
Samir K Saha, Ph.D.Department of Microbiology
Dhaka Shishu HospitalBangladesh
Typhoid Fever:Salmonella enterica Serover Typhi.
• Endemic in Indian Subcontinent• Diagnosis: Often jeopardized.• Treatment: Become a challenge due to drug
resistance.• Prevention: Should be planned properly.
• Sanitation• Vaccine
Laboratory Diagnosis of Typhoid fever
• Blood culture – Gold standard– Limitations: only 50-60% of the cases are
positive in the first week of disease.• Serological: Widal test. • Stool and/or Urine culture
– Both of them are rarely positive and stool culture needs special procedure.
Serological tests• Widal widely used test in the endemic region.
Cut off point – Varies from place to place and time– Significance for diagnosis and prognosis
• Bangladesh Perspective – TO ≥1:160 and/or TH ≥1:320
• Clinical correlations – Non-specific reactions, previous clinical/subclinical infections.– Common questions ………
Saha et al. 1997. Annals of Trop Pediatrics
BLOOD CULTURE AND RECENT ADVANCES.
♣Conventional•Time consuming
♣ Advance technologies: FAN, Vitek, Bactech etc.• Expensive and Needs Automation.
♣ Lysis-direct plating/centrifugation method.
Schematic diagram of LDP/LC method.
♣The device is made indigenously.
♣ Method is simple.
♣ Can be adapted in any lab with minimum facilities.
Growth of S. typhi after 18 hours of incubations.
Blood culture during antibiotic therapy?
• Introduction of any Newer method that usually accompanied with loud fanfares and intensive promotions.
• What is the reality?– Sensitivity of the organisms– Culturable and non-culturable form of bacteria.– Pharmacokinetics of antibiotic(s)
Saha SK, et al. 1991. Applied Environmental Microbiology. 57(11): 3388-9
Growth from a partially treated case.
Saha et al. 1992 Trans. Royal Society Tropical Medicine and Hygiene.
Turnaround time for Culture Positive Cases (N=391).
• TAT – Key to create impact on treatment.
• TAT90 was 30 h• TAT100 was ≤67 h• Antibiogram of
randomly selected strains were tested by conventional NCCLS method.– The result was identical
(±1mm).
Saha et al. 2001. Journal of Clinical Microbiology.0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%<=67h<=54h<=47h<=30h
Impact of Report on Therapy.Empirical Therapy Started Change
Needed from 1st line to 2nd
line.
Change Needed from 2nd line to 1st
line.17% (8/47), which was done on the next day.
83% (33/40) would be changed to 1st
line.
Appropriate Therapy after getting report
81% (87/108) 19% (21/108)
54% (47/87) with 1st line of antibiotic
46% (40/87) with 2nd line of antibiotic
Overall impact is only on 27% [29(21+8)/108] of cases.
Cost effectiveness was never a consideration.
Treatment of typhoid fever• 1st line of Antibiotic
– Amoxycillin– Chloramphenicol– Cotrimoxazole
• Recent Problem– Slow epidemic of multi-
drug resistant S. Typhi in the subcontinent
• 2nd line of antibiotic– Ceftriaxone - Expensive– Ciprofloxacin – Widely Used
62
0
10
20
30
40
50
60
MDR (1992-93)
Saha et al. 1995 J Antimicrobiol Chemotherapy.
• Panic among the public health people
• Confusion between clinicians and microbiologists
Impact of using 2nd line of drugs - Resistance of community vs hospital strains, 1994-1997
71
56
3330
40
26
16 13
0
10
20
30
40
50
60
70
80
1994 1995 1996 1997Years
% o
f M
ultid
rug
res
ista
nt s
train
s DSH
PDC
• Remarkable difference between hospital and community isolates.
• Ideal practice in Bangladesh and ….• Hospital Vs community
Saha et al. J Antimicrobial Chemotherapy 1997
Nalidixic Acid Resistance in S. typhi
0
10
20
30
40
50
60
70
80
1998 1999 2000 2001 2002 2003 2004
No.
of c
ases
• Progressive increase in relative resistance to Ciprofloxacin– Delay in clinical
response– Higher dose– Treatment failure– Recurrence
Trend of drug resistance in last one decade
11
29 2933
72
6257
7
14 14
22
34
4144
1998 1999 2000 2001 2002 2003 2004
71
56
3330
40
26
1613
0
10
20
30
40
50
60
70
80
1994 1995 1996 1997
% o
f M
ultid
rug
resi
stan
t st
rain
s
HospitalCommunity
Prevention• Improvement of sanitary system and
assurance of safe water supply. • Immunization – designed for school age
children– Common belief – either not prevalent or benign
in early age
• Vaccine type– Parentaral
• LPS – age group dependent– Oral
• Attenuated
Magnitude of S. typhi bacteremia : change in concept of virulence
31
2322
1516
11
7
0
5
10
15
20
25
30
35
1-12m 13-24m 25-36m 37-48m 5-9y 10-19y 20y
• Magnitude of Bacteremia is directly proportional to age.
• Disagree with the common belief about – Virulence– vaccination.
Saha et al Pediatric Infectious Disease Journal, 2000
Age group distribution of Typhoid cases 1998-2004: Implication in vaccination policy (N=2074)
15
19
32
44
54
78
92
100
0
20
40
60
80
100
120
0-5m 0-11m 0-23m 0-35m 0-47m 0-59m 0-9y 0-19y All age
Recommended age of vaccination
Conjugate vaccine needed for this group
New recommendation for vaccination.Existing vaccine will
not be effective in 19% of cases
98% coverage
19%
With effective
conjugate vaccine
Saha et al Pediatric Infectious Diseases Journal, 2000; and unpublished
Conclusions• Prevalence – Most common cause of febrile
illness in the community and hospital• Treatment – Third generation cephalosporin• Prevention – Vaccination, Sanitation,
Education (?)– Vaccination policy – conjugated vaccine at the
age of 9 months to 1 year
Recommended