August 24 th & 25 th 2012
Mid-term Meeting of IAPCOI,
The Hyatt Regency Hotel, Mumbai
Vipin M. Vashishtha, MD, FIAP
Convener, IAPCOI 2011-13 vipinipsita@gmail.com

Crude typhoid fever incidence rates by region, 2000

Incidence rate of typhoid fever in
Asia: comparison of 2 multi-centre trials

Kothari et al. The burden of enteric fever 259 J Infect Developing Countries 2008; 2(4): 253-259.

Age-specific incidence of culture-proven typhoid fever from population-based studies
Bhan MK , Bahl R , Bhatnagar S . Typhoid and paratyphoid fever. Lancet.
2005 2;366(9487):749-62.

Characteristics and incidence of typhoid fever from the study sites: Age group
Site
Typhoid
Incidence
(per 100000/yr) by age
0- 1 years
Hechi,
China
Kolkata
India
North
Jakarta
Indonesia
15.3
214.2
81.7
NA 89.2
0.0
2- 4 years
5- 15 years
≥ 16 years
NA
29.3
12.4
340.1
493.5
119.7
148.7
180.3
51.2
Karachi
Pakistan
451.7
NA
573.2
412.9
NA
Hue,
Viet Nam
Total
21.3
NA
NA
24.2
10.9
107.6
21.6
364.8
170.8
46.8
Ochiai RL, Acosta CJ, Danovaro-Holliday MC et al. (2008) A study of typhoid fever in five Asian countries: disease burden and implications for control. Bull World Health Organ 86(4):260-68.

How big is the paratyphoid burden?

Trends in S. Paratyphi A, Safdarjung
Hospital (S. Typhi vs. S. Paratyphi A)
J Infect Dev Ctries 2010; 4(6):404-411.

Global distribution of antimicrobial resistance in S typhi (1990–2004)

Rates of Antibiotic Resistance among S. Typhi Isolates from Five Asian Study Sites in the DOMI Programme

Studies reporting high-level ciprofloxacin resistance in S.
typhi & S. paratyphi A in India
Harish BN, Menezes GA. Indian J Med Microbiol. 2011 Jul-Sep;29(3):223-9.

 Bijnor a small city of western Uttar Pradesh, a northern state of India

Mangla Hospital & Research Center
District population (2007): 3.4 million
 Decadal population growth (2007)= 27.16%; UP=25.8%,
India=21.34%
 Birth rate: 460 per 10,000; UP=382, India=268
 Females ratio: 896 per 1000 males, UP=898; Inia=933
 Delivery at hospitals/nursing homes: 28.7%; India=
40.7%

A sentinel site surveillance of 10 VPDs

Total OPD cases,
March 2011-May 2012 cases
2500
2000
1500
1920
1745
1990
1920
2080
1840 1920 1760
2085
1920
1760
1840
2000
1910
1295
1000
500
0
Mar Apr May June July Aug Sept Oct. Nov Dec Jan Feb Mar Apr May

450
400
350
300
250
200
150
100
50
0
MHRC: 10 VPDs: Mar 2011-May 2012* (N= 27985)
382
30
17
40.9% of all 10 VPDS!!
105
90
98
60
137
3
11
ABM
Chikenpox
Dengue
Diptheria
Enteric fever
Hepatitis
Measles
Mumps
Pertusis
Pneumonia
* Till May 18, 2012

Age group of typhoid cases
(N=382)
100
80
60
40
20
0
180
160
140
120
3
0-1 yr
28
119
155
68
9
2 -5 yr 5 - 10 yr 10 - 15 yr Above 15 1- 2 yr
0-1 yr 1- 2 yr 2 -5 yr 5 - 10 yr 10 - 15 yr Above 15

359
Immunization status
(N=382) cases
9
14
Fully Immunized
Partially Immunized
Not Immunized

Seasonal breakup:
March 2011-May 2012
Cases
60
46
42
50
50
40
34
29
33
30
20
19
14
17
11 11
28
16
20
12
10
0
Mar April May June July Aug Sep Oct Nov Dec Jan Feb Mar April May

Arguments against significant typhoid burden in India

Significance of Typhoid in India*
*Mathew JL. Conjugate typhoid vaccine(s) in the Indian context.
Indian Pediatr.
2009
Feb;46(2):182-4.
• 1. Ochiai RL, Acosta CJ, Danovaro-Holliday MC, Baiqing D, Bhattacharya SK,
Agtini MD, et al. A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull WHO 2008; 86: 260-268.

Justification for Typhoid vaccination
Problem - I
Globally about 21.6 million cases every year, causing about 2.1 lac deaths
But estimates indicate 33 million cases
90% of all cases and deaths in Asia, rest in Africa and
Latin America
Problem – II
Multi drug resistance
Problem – III
Changing age scenario – infants and toddlers equally affected

Do we have ‘effective’ typhoid vaccine to issue recommendations on widespread use?

Orphan disease & Neglected vaccine!!

• Evidence from Cuba, Iran, Thailand, Malaysia,
Vietnam, & China confirms that a one-dose, Vi-
PS vaccination strategy targeting a wide age range can effectively control disease
• However, only 6 countries currently have school or community-based typhoid vaccination programs

Vi-PS typhoid vaccine has shown effectiveness in India!!
• In a recently published cluster randomized effectiveness trial conducted in over 40,000 subjects in urban slums of Kolkata, the overall
effectiveness of the vaccine at 2 years follow up was 61%, and in children below 5 years was 80%
• Interestingly the herd protection of 44% was noted in unvaccinated children in the vaccinated cluster as compared to the control cluster
Dipika Sur, R. Leon Ochiai, et al. A Cluster-Randomized Effectiveness Trial of Vi Typhoid Vaccine in India. N Engl J Med 2009;361:335-44.

What about the currently available
Indian Vi-PS conjugate vaccine? Does it have any role? Can we improve it further?

What about the currently available
Indian Vi-PS conjugate vaccine?
Does it have any role? Can we improve it further?

What is the pipeline for next generation typhoid vaccines?

Geographic Representation of Typhoid
Vaccination Programs
Despite recommendations, typhoid vaccines are significantly underutilized!!!

Barriers to widespread typhoid vaccine use:
Other potential challenges:
• Paratyphi burden?
• Lack of WHO prequalified vaccines
• Country political will
• Managing typhoid as a communicable disease rather than within the immunization system
• Current focus on Hib, pneumococcal, and rotavirus vaccine introduction in GAVI countries

How can IAPCOI help in prevention of
Typhoid fever in India?
Can we initiate a collaborative project with international agencies/institutions?
What level of support/commitment is required?