DIAGNOSIS AND TREATMENT OF TYPHOID FEVER IN THE CHILDREN
Transcript of DIAGNOSIS AND TREATMENT OF TYPHOID FEVER IN THE CHILDREN
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.
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
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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