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