Rotavirus Vaccine Impact Beyond Preventing Diarrhea

Samir K Saha, Ph.DChild Health Research Foundation

Dhaka Shishu HospitalDhaka, Bangladesh

Barriers to Rotavirus Vaccine Introduction

13th International Rotavirus Symposium, 2018Minsk, Belarus29 – 31 August

1

BANGLADESH – Achieved MDGs ahead of time

2

Bangladesh – a pro-vaccine country with remarkable success in EPI programme

• Introduced Hib vaccine in 2009

• Pneumococcal vaccine in 2015

3

Leading infectious causes of mortality, 2000 estimates

Dea

ths (

mill

ions

)< 5 years old > 5 years old

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Pneumonia AIDS Diarrhoea TB Malaria Measles

3.5

2.7

2.2

1.7

1.1 0.9

Source: WHO 4

1. The world is changing – specifically the developing worldVaccine Preventable Diseases

5

Our Days in the Laboratory in 1980s

• Diphtheria cases everyday• Tetanus was not uncommon• Pneumococcus and Hib disease were enormous though only few

laboratories could detect them

6

Country-specific mortality rates and deaths attributable to Pneumococcus and Hib in 2015

Wahl et al Lancet Glob Hlth 2018

• Two vaccines have saved 1.45 million children’s lives in the last 15 years

7

Pneumococcus Hib

2. The world is changing – specifically the developing worldVaccine uptake vs graduation of low income countries

8

50% coverage**

Years from availability

Million doses

0

50

100

150

200 HepB – 75 lowest income countries

Hib - 75 lowest income countries

1 3 5 7 9 11 13 15 17 19 21 23

33% coverage**

ESTIMATE

10% coverage**

50% coverage**

9

Delayed Uptake of Available Preventives

Growth of the Low Income /Emerging Countries

10

Source: International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Vaccine Information Management System (VIMS), data as of Sep 2015. Coverage based on WUENIC data, upd. as of Aug 2015.

0%

10%

20%

30%

40%

50%

60%

70%

2008 2009 2010 2011 2012 2013 2014

PCV

Cove

rage

(%)

High income Upper-middle income Lower-middle income Low income

PCV-7 PCV-10/13

PCV Coverage, by Income Group

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3. The world is changing – specifically the developing world

MDG SDG1990 2015 (MDG 4)

/year 12.7 million 5.9 millionAiming to achieve “Good Health and Wellbeing” SDG 3

Levels and Trends in Child Mortality, WHO 201512

Barriers to Rotavirus Vaccine Introduction

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Global Rotavirus Mortality Over Time• Remarkable decrease in

mortality• Specifically South Asia –

Bangladesh

Troegel et al JAMA Pediatr 2018 15

Under-5 Deaths per 1,000 live births

Bangladesh Demographic and Health Surveys, 2004 & 2011

Bangladesh - Most of the causes of <5 deaths are declining – remarkably diarrhoea

16

Proportion of <5 death due to Pneumonia and Diarrhea in Bangladesh

0

5

10

15

20

25

1993 1997 2004 2011

% o

f dea

th

Year

Diarrhoea

Pneumonia

Source: Liu et al. Population Health Metrics 2011, BDHS 2011 17

Hesitancy among the policy makers – Why?

• Minimal or no deaths from Rotavirus cases• Patients are leaving hospital within 24 – 48 hrs• Has the concern about the continuation of PCV beyond Gavi eligibility

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We explored the burden of Rotavirus and possible impact on “Health System”

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0

2

4

6

8

10

12

14

16

Perc

enta

ge 13%

; 3,0

21

Admission at Dhaka Shishu Hospital (N=23,064) – the largest pediatric hospital (2017)

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Rotavirus surveillance at Dhaka Shishu Hospital, Bangladesh during July-December, 2012. • 54% (159/297) were rotavirus-positive

among the enrolled cases.

• <3 months of age: 58% (19/33).

• <1 year: 51% (105/204)

• <2 years: 53% (137/258)

Rotavirus among acute watery diarrhea

19

86

32

22

14

85

2217

12

66

86

100

10

72

88

100

0

10

20

30

40

50

60

70

80

90

100

0

10

20

30

40

50

60

70

80

90

100

<3m 3-11m 12-23m 24-59m

Cum

ulat

ive

perc

enta

ge

Freq

uenc

y (n

umbe

r)

Age

Rota-positive

Rota-Negative

Cum. Rota(+)ve

Cum. Rota(-)ve

Tanmoy et al 2016 (PLoS One)

Arif Tanmoy

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Rotavirus surveillance at Dhaka Shishu Hospital, Bangladesh during July-December, 2012. • Prevalent genotypes:

• G12P[8] (35%; 55/159).• G1P[8] (29%; 46/159)

Circulating genotypes among rotavirus positive cases.

Tanmoy AM et al 2016 (PLoS One)

56

46

1310 8 7

4 3

11

10

10

20

30

40

50

60

Freq

uenc

y

GenotypesGagandeep Kang

22

0

2

4

6

8

10

12

14

16

Perc

enta

ge 13%

; 3,0

21

Admission at Dhaka Shishu Hospital (N=23,064) – the largest pediatric hospital (2017)

• In 2017 to 23,000 admission, 15% of them are pneumonia

• Rotavirus diarrhea (13%) also a predominant cause of hospitalization

• However, 97% of cases are discharged within 48 hours.

• Based on such data, vaccines against pneumonia and meningitis have rightly been prioritized.

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• Fierce competition for beds in public hospitals

• At Resource poor setting, only 3 beds per 10,000 population, in comparison to 31 in the US

• This leading to refusal of cases, just by putting a stamp

• “BED NOT AVAILABLE” • huge burden on Health

System

• In 2017 to 6000 admissible cases were refused

• A huge burden on the “Health System”

• Refused cases are more severe and vulnerable to deaths and disabilities

• Care seeking issues

1615

13

76 6

4 3 3 3 3 21 1 1 1 1 1 1 1 1

0

2

4

6

8

10

12

14

16

18

Pneu

mon

iaSe

vere

per

inat

al a

sphy

xia

Acut

e ga

stro

ente

ritis

Pre-

term

low

birt

h w

eigh

tN

eona

tal s

epsis

Bron

chio

litis

Febr

ile c

onvu

lsion

Seps

isN

eona

tal j

aund

ice

Ente

ric fe

ver

Men

ingi

tisN

ephr

otic

synd

rom

eDy

sent

ery

Cong

enita

l hea

rt d

iseas

eSe

izure

diso

rder

Anae

mia

Tach

ypne

a of

new

born

Inte

stin

al o

bstr

uctio

n et

c.U

rinar

y tr

act i

nfec

tion

Prot

ein

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gy M

alnu

triti

onEn

ceph

aliti

s

Impact of Rota on the health system-possible impact of vaccine

24Saha et al Am J Trop Med Hyg, 2018

• 3000 cases of AGE 1500 RV cases ~700 cases will be prevented by Rotavirus Vaccine

• We will able accommodate at least 500 potential serious cases

• Mostly with meningitis, asphyxia and preterm

Impact of Rota on the health system-possible impact of vaccine

Senjuti Saha

Saha et al Am J Trop Med Hyg, 2018

1615

13

76 6

4 3 3 3 3 21 1 1 1 1 1 1 1 1

0

2

4

6

8

10

12

14

16

18

Pneu

mon

iaSe

vere

per

inat

al a

sphy

xia

Acut

e ga

stro

ente

ritis

Pre-

term

low

birt

h w

eigh

tN

eona

tal s

epsis

Bron

chio

litis

Febr

ile c

onvu

lsion

Seps

isN

eona

tal j

aund

ice

Ente

ric fe

ver

Men

ingi

tisN

ephr

otic

synd

rom

eDy

sent

ery

Cong

enita

l hea

rt d

iseas

eSe

izure

diso

rder

Anae

mia

Tach

ypne

a of

new

born

Inte

stin

al o

bstr

uctio

n et

c.U

rinar

y tr

act i

nfec

tion

Prot

ein

Ener

gy M

alnu

triti

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aliti

s

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What are we doing now?

• Pre-vaccine• Measuring the burden of AGE• Proportion of cases with Rotavirus• Keeping track of all refusal cases irrespective of clinical diagnosis

• Refused cases will be followed up and outcome will be recorded• These will be used as baseline data

• Post-vaccine• Vaccine impact will be measured based on the combination of admission and

refusal data• Not just based on the admissions from the “administrative” data – as it was

done in the past

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0

2

4

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Ger

man

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UK

Denm

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Net

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land

New

…Sp

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Aust

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Cons

ulta

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Tim

e (m

in)

Countries

One Step Further• Consultation time

• Ranged from 48 sec to 22 mins• We are aiming for it too!

BMJ Open November 2017; 7(10): e017902 27

Conclusions• Introduction of Rotavirus vaccine will prevent deaths and disabilities

of non-Rota cases - who are getting refused due to lack of beds• Rota vaccine will facilitate the prevention of deaths and disabilities of

the cases with meningitis, severe pneumonia and birth asphyxia, preterm babies

• Expedite the achievement of SDG3• New Strategy of Advocacy to convince policy makers

• Based on multi-dimensional changes in the world our advocacy to convince the policy makers need to be changed

• Need to focus on improvement of health system, not limiting to prevention of disease specific deaths

• This concept is not specific for Rotavirus vaccine but also other diseases like RSV, Typhoid, etc.

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Acknowledgements

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