School based typhoid fever School based typhoid fever immunisationimmunisation..Prospects & problems Prospects & problems

T. Jacob JohnVellore, India

Background document: The diagnosis, treatment and p revention of typhoid fever World Health Organization, WHO/V&B/03.07

UK: Lessons from successfulschool based vaccination programs

�Routine rubella at 13 yrs of age: 1971-1994

�BCG at 10-14 yrs: 1953-2005

�dT booster at 13-18 yrs: 1960 onwards

�Nationwide campaign measles/rubella at 5-16: 1994

�Mening. C campaign at 5-18 yrs: 1999-2000

�All “voluntary” and free of charge

Viet Nam: success storySchool based vaccination.

�Measles vaccination by school based campaign in 2002-2003:

�Coverage achieved: 99%

�When governments apply their minds and money, programs succeed

�The secret is to enable and ensure accountability to be accepted by governments

Many successful demonstration projectsof school based typhoid fever vaccination

�Viet Nam (Hue city: DOMI study, Vi)

� Indonesia (DOMI study Vi)

�Pakistan (DOMI study Vi)

�Chile (M Levine studies – Ty21a oral)

�No doubt projects work; up scaling and institutionalizing for sustainability not yet proven

�What happens in 2nd yr and thereafter?

Statement of principle

�School based vaccination, or any vaccination modality in public health, is not an end in itself, but a means to an end.

�Unless we define the “end” and apply methods of measuring it by stated time-target, and of monitoring it en route, we may look like “peddlers of product” and not “preventers of pathology” (that we really are)

�Unless “we” – them and us, can celebrate disease prevention, we cannot expect demand creation from them -- and the Sisyphean curse will not be cured.

National Family Health SurveyNearly 200,000 interviewed

Immunisation coverge %

1992-93 1998-99 2005-06

Uttar Pradesh: 20 20 23

Bihar: 11 12 33

National: 35 42 44

Delhi slum and Tamil Nadu village

� Lancet 1999; 354: 734 (A Sinha, MK Bhan) showed incidences of:

<5 yrs: 27/1000 person yrs5-19 yrs: 12/1000 person yrs19-40 yrs: 1/1000 person years (in urban, overcrowded slums in Delhi, with piped water supply, often contaminated with coliforms)

� M Datta, unpublished:

In rural community, overall incidence 1/100 of Delhi data.No case < 19 years of ageEvery adult case had h/o visit to Chennai and eating in restaurantLocal bore well water system, with or without tank storage.

EPIDEMIOLOGY

Typhoid fever, a severe disease present all over the world

Endemic mode Sporadic modeEndo-epidemic mode

•• PrevalentPrevalent worldwideworldwide -- SalmonellosisSalmonellosis increasingincreasing•• Incidence Incidence alwaysalways higherhigher in in studiesstudies for vaccine for vaccine efficacyefficacy

-- 16 16 -- 33 million cases / 33 million cases / yearyear worldwideworldwide (1, 2))(1, 2))

-- DevelopingDeveloping world : 540 / 10world : 540 / 10 55 / / yearyear

-- DevelopedDeveloped world : 0.2 / 10world : 0.2 / 10 55 / / yearyear

((HighestHighest : Papua New : Papua New GuineaGuinea : 1208 / 10: 1208 / 105 (1)5 (1)

IndonesiaIndonesia : 810 / 10: 810 / 105 (3)5 (3)

-- 0.5 to 0.7 million 0.5 to 0.7 million deathsdeaths / / yearyear((mortalitymortality AsiaAsia : 12 : 12 -- 32 %)32 %)

1. Tikki Pang et al., Typhoid fever and other Salmonellosis: a continuing challange, Trends in Microbiology, Vol.3, No 7, July, 1995; pp 253-255.2. Levine MM. Typhoid Fever Vaccines. In: Plotkin S.A., Mortimer EA, Editors. Vaccines, Philadelphia, Saunders. 1994: 597-633.3. Simanjuntak CH et al. Oral Immunization against typhoid fever in Indonesia with Ty21a Vaccine Lancet 1991; 338:1055-59.

TYPHOID FEVER TYPHOID FEVER -- THE PROBLEM THE PROBLEM

•• Incidence in Incidence in AsiaAsia :: 1000 / 101000 / 105 5 / / yearyear (1)(1)

•• Cases in South East Cases in South East AsiaAsia :: 4.36 4.36 -- 6.98 million / 6.98 million / yearyear

•• MortalityMortality in in AsiaAsia :: 12 12 -- 32 % (32 % (despitedespite treatmenttreatment ))

•• TravelTravel relatedrelated typhoidtyphoid :: IndiaIndia : 105 : 105 -- 118 / million travellers / 118 / million travellers / yearyearSE SE AsiaAsia : 7.2 / million travellers : 7.2 / million travellers (2)(2)

1. Bernard Ivanoff, Typhoid Fever: Global Situation and WHO Recommendations. Southeast Asian Journal of Tropical Medicine and Public Health, Vol 26 Suppl. 2, 1995, pp.1-6

2. Editorial, Typhoid Vaccination: weighing the option, Lancet; Vol. 340: Aug 8, 1992, 341-342

TYPHOID IN ASIATYPHOID IN ASIA

- Among the highest in the world- Incidence : 1206 / 10 5 / year

600,000 - 1300000 cases / year

- Mortality : >20,000 deaths / year

- Age : 91% of cases in 3 - 19 years age

Simanjuntak Cyrus H et al. Oral Immunization against typhoid fever in Indonesia with Ty21 a Vaccine, Lancet 1991; 338:1055-59.

EPIDEMIOLOGIC SITUATION: INDONESIAEPIDEMIOLOGIC SITUATION: INDONESIA

• Most cases in children and young adults (1)

Peak : 5 - 20 years age

80% : < 40 yeas age

1 - 4 years age < 5 - 9 years age group(Despite a similar risk of exposures) (2)

Source :

1. Michael L Bennish, Immunization against Salmonella typhi. Infectious Diseases in Clinical Practice,

Vol.4, No.2.

2. Mahle WT, Levine MM : Salmonella typhi infection in children younger than five year of age.

Pediatr Infect Dis J 1993, 12: 627-631.

TYPHOID FEVER TYPHOID FEVER –– RISK BY AGERISK BY AGE

Incidence according to ageIncidence according to age

0

50

100

150

200

250

300

Inci

denc

e (p

er 1

00,0

00)

0-4years

10-14years

20-24years

35-44years

55-64years

Age groups

Typhoid fever

Levine M.M. et al., PAHO; 1985: 37-53. Chile 1977-1981

EPIDEMIOLOGY: ENDEMIC AREAEPIDEMIOLOGY: ENDEMIC AREA

0

10

20

30

40

50

60

< 1 year 1-4 year 5-14 years 15-44 years > 45 years

0

10

20

30

40

50

60

1965 1991(b) 1991(a)

AGE DISTRIBUTION: INDIAAGE DISTRIBUTION: INDIAC

ase s

/ 10

5 P

opu l

atio

n

A. K. DUTTA et al., Typhoid Fever - an Asian perspective, APPSPGAN Teaching Workshop, Galle, Sri Lanka, October, 1998

• Age : Shift to the left (upto 60% < 5 years age)

• Many < 2 years age

• Variable clinical picture in young children

• Either typhoid-like (>2 yrs) or not so (<2 yrs)

• Common presentation: fever, diarrhoea

pain abdomen, refusal to feed, seizures,

radiological bronchopneumonia,

pronounced hepatosplenomegaly, no leukopenia

• Blood culture not often done in young children

Johnson A, Aderle WI, Enteric fever in childhood, J. Trop. Med. Hygiene 1981, Vol. 84, 29-55

Pandey KK, Srinivasan S, Typhoid fever below 5 years, I nd. Pediatr., 1990 Vol. 278, 153-156

TYPHOID FEVER (TYPHOID FEVER (ChildrenChildren ) ) THE DISEASE PROFILETHE DISEASE PROFILE

1948 : 1st successful treatment with Chloram.1950 : 1st resistance to Chloram. - England1960 : Worldwide Chloram. resistance1960 - 1984 : Increasing resistance to front line

drugs (TMZ, Ampicillin/Amoxy.)1984 : MDRST reported in Thailand1987 : MDRST - China1990 : MDRST - India1991 : MDRST - Malaysia and Pakistan

1997 : 1st reports of Quinolone resistance

MDRST : MDRST : MicrobiologicalMicrobiological : > 2 : > 2 antibioticsantibiotics in vitro in vitro ClinicalClinical : All : All threethree 1st line 1st line antibioticsantibiotics

TYPHOID TYPHOID -- THE CHANGING PROFILE THE CHANGING PROFILE ((MicrobiologicalMicrobiological ))

MDRST :MDRST : 40 - 50 % in Children15 - 50 % in Children < 5 years age

COUNTRYCOUNTRY % ISOLATES% ISOLATES

• INDIA : 40 - 92 %• PAKISTAN : 20 - 77 %• VIETNAM : 50 - 88.7 %• CHINA : 50 %• SINGAPORE : 16 - 25 %• KUWAIT : 5 %• IRAN : 37 %

TYPHOID TYPHOID -- THE CHANGING PROFILE THE CHANGING PROFILE ((MicrobiologicalMicrobiological ))

• Prolonged Pyrexia upto 8 weeks

• Marked Toxaemia

• Increased incidence of Diarrhoea

• Increased incidence of Tender HSM

• Higher incidence of Complications- Acute nephritic Syndrome- D.I.C.

TYPHOID TYPHOID -- THE CHANGING PROFILE THE CHANGING PROFILE (MDRST)(MDRST)

The unjust world of typhoid fever

�Where governments neglect their unavoidable responsibility to prevent and control diseases…

�Where treatment cost is left as the responsibility of the unfortunate person with disease…

�Whereas we declare that health is human right…�The obvious minimum action we must promote is

prevention by vaccination, by the govt. health system, in school and outside school, as the inalienable right of the people.

School based vaccination is appropriate,where,

�Disease prevention is a priority, and --

�Disease incidence is high in the relevant age group

�There is a health policy (national/local) to control the disease by vaccination

�School based vaccination is a part of the whole –(where typhoid fever is frequent in pre-school age and it is included in national vaccination program)

�Not perceived as “marketing tactic” only

Who are the involved parties?

� The health system (Public health, EPI, government)

� The school system: Public sector / private sector

� The school health system

� Parents of children (understand, accept, consent?)

� The children themselves (understand, accept, consent?)

� The professional association of care-givers: Pediatrics; public health; nurses

� The public (and the media that inform the public)

What are the components of TF control?

� (S. typhi rarely amplifies in environment; large inoculum via fecal contamination in water?)

� What are the elements of control?

� How does vaccination fit in? Which vaccine?

� Vi first (all ages) and Ty21a later?

� Which are special groups other than school children?

� One time catch up (Vi), followed by systematic vaccination of new age cohorts? What age? Which vaccine?

� Food hygiene, water quality, what else?

“Visibility, consensus and action plan”What is the measurable objective?

� Bad disease� Costly to treat, impoverishing individuals/nations� Common disease, but we have not unraveled the variations

in risk/prevalence frequencies. � Location-specific real-time data can come only from a functional

disease surveillance system� Must be controlled: What is the definition?� May be “eliminated” in local communities � Could (theoretically) be even eradicated� But who will champion our cause? Rich countries and the rich in poor

countries have very low risk.

THANK YOUTHANK YOU

Estimation of the number of annual casesEstimation of the number of annual cases

Cases ofCases ofTyphoid feverTyphoid fever

IncidenceIncidenceraterate

AfricaAfrica 4 375 0004 375 000 9.3/9.3/0000

West AsiaWest Asia 749 000749 000 7.6/7.6/0000

South and East AsiaSouth and East Asia 6 980 0006 980 000 5/5/0000

South AmericaSouth America 406 000406 000 1.1/1.1/0000

Edelman R. et al., Rev. Infect. Dis., 1986, 8:329-3 49

EPIDEMIOLOGY: ENDEMIC AREAEPIDEMIOLOGY: ENDEMIC AREA

COUNTRY INCIDENCE CFR

INDIA 500 / 105 (1994)992 / 105 (1997)

1.1 %

PAKISTAN 150,000 cases/year(1990 - 1994)

-

INDONESIA 350-810 / 105 (1995) 10 %

SINGAPORE 5.9 / 105 (1989)1.2 / 105 (1997)

Nil

THAILAND 12 / 105 (1992) 1 %

MALAYSIA 4.46 / 105 (1994) 0.88 %

TYPHOID IN ASIATYPHOID IN ASIA

•• TyphoidTyphoid isis 5th 5th mostmost commoncommon communicable communicable diseasedisease

•• 1979 1979 -- 1988 : 300,000 cases ; 1000 1988 : 300,000 cases ; 1000 deathsdeaths ??????

•• 1973 : Incidence : 7 . 6 / 1000 ( 1 1973 : Incidence : 7 . 6 / 1000 ( 1 -- 15 15 yearsyears age group )age group )

2.5 million case / 2.5 million case / yearyear

1. Dutta AK, Kanwal S, Nguyen VH, Wood Susan, A stud y of the cost burden of typhoidfever to an individual in India; Ind. J. Clin. Prac., Vol.9, No. 3, Aug’98, 16-29

2. Ichhpujani RL, Bhatia R. Typhoid Fever, First Edit ion 1997, Top Publications - Delhi

EPIDEMIOLOGIC SITUATION: INDIAEPIDEMIOLOGIC SITUATION: INDIA

Temptations, to be avoided

�To promote the “ritual” and forget the “spirit”

�To exploit opportunity of captive target

�To think “now” and forget sustainability

�Not to plan well, create ambience, reduce anxiety, preparedness to face adverse reactions – immediate and subsequent

�Not to be legally correct, not only morally right

�Not to be transparent