Oral Cholera Vaccines: An Investment Case

Transcription

1 Oral Cholera Vaccines: An Investment Case Brian Maskery, Ann Levin, Denise DeRoeck, Young Eun Kim, Mohammed Ali, Colleen Burgess Anna Lena Lopez, Tom Wierzba, Sunheang Shin, John Clemens WHO- SAGE April 7,

2 Why a global investment case? To provide a global evidence base for invessng in oral cholera vaccines (OCVs) as part of a larger strategy that includes improvements to water and sanitason directed to: Global donors and other decision makers (GAVI, WHO HQ, UNICEF, World Bank) Regional donors and decision makers (regional WHO, regional development banks) NaSonal and state- level governments Local industries affected by cholera outbreaks ExisSng cholera vaccine suppliers and potensal market entrants The investment case focuses on vaccinason against endemic cholera 2

3 Killed whole cell (WC) oral cholera vaccines rbs- WC (Dukoral) Killed whole cell vaccine + B (binding) subunit of cholera toxin Requires buffer ( ml) Vaccine efficacy of 60% sustained over 2 years Cost per dose to the public sector depends on volume ($4.70 afer tsunami) 2 doses for age>5 yrs. and 3 doses for age 2-5 yrs. WHO prequalified WC- only (Shanchol/mORC- Vax) Whole cell only vaccine; no cholera toxin B subunit No buffer required Vaccine efficacy of 67% sustained over 3 years (based on latest data) Current price/dose of Shanchol to public sector is $ doses for age 1+ Shanchol applicason for prequalificason under considerason 3

4 What is the global disease burden? 51 countries are defined as cholera- endemic countries, having reported cholera during at least 3 yrs. out of a recent 5- year period based on a literature review including WHO, ProMED, and other data 18 countries are defined as non- endemic countries based on being located in regions with endemic countries and with reports of cholera in at least one year from Use populason lacking access to improved sanitason as proxy for % at- risk for cholera by country Used 2005 UN populason data and Millennium Development Goal Indicators database Endemic regions include AFR, EMR, SEAR, and WPR 4

5 Annual cholera incidence (per 1,000 populason) in study sites in four countries N. Jakarta, Indonesia 9/01-7/ Kolkata, India 5/03-4/05 Matlab, Bangladesh < 5 years old 5-14 years 15 and over All ages Beira, Mozambique* 12/03-1/04 PopulaSon included in study DuraSon of study 160,257 58,063 ~200,000 19,547 2 years 2 years 10 years 1 year Deen J, et al. PLoS Negl Trop Dis Feb 20;2(2):e173. 5

6 EsSmated incidence rates (51 endemic countries) India Malaysia Philippines Seychelles Comoros Indonesia Incidence rate (/1,000) >=2.0 per 1, per 1, per 1,000 <0.5 per 1,000 Non-endemic 6

7 AssumpSons for cholera case- fatality rates (CFR) WHO sub-region Case fatality (%) AFR-D 3.8 AFR-E 3.8 EMR-B 1.3 EMR-D 3.2 SEAR-B 1.0 SEAR-D* 3.0 WPR-B 1.0 *Bangladesh estimated with country specific methodology Literature reports of cholera CFRs range from 0.3% to 13.6% 7

8 EsSmated cholera cases requiring treatment: ~3 million cases per year Es?mated cases in endemic countries WHO region <1y 1-4y 5-14y 15y+ Total AFR 160, , , ,744 1,411,453 EMR 19,192 71,041 47,243 51, ,793 SEAR* 102, , , ,789 1,224,368 WPR 846 3,287 2,785 5,137 12,055 TOTAL 282,688 1,030, , ,987 2,836,669 *Bangladesh estimated with country specific methodology In non-endemic countries, estimated cases are 87,246. 8

9 EsSmated deaths due to cholera: ~94,000 deaths per year Es?mated deaths in endemic countries WHO region <1y 1-4y 5-14y 15y+ Total AFR 6,096 21,655 13,656 12,225 53,632 EMR 613 2,267 1,507 1,633 6,020 SEAR* 2,665 10,132 8,108 10,813 31,718 WPR TOTAL 9,382 34,086 23,299 24,723 91,490 *Bangladesh estimated with country specific methodology In non-endemic countries, estimated deaths are 2,506. 9

10 Which countries are more likely to adopt and when? Semi- quanstasve scoring system and qualitasve adjustment to predict country adopson Independent variables: Reported and modeled cholera mortality AdopSon history (Hib, Hep- B, pneumo (applicasons to GAVI)) Performance of the EPI (MCV coverage) Previous cholera research in country (surveillance, clinical trials, demonstrason projects) Assume that each country adopts in increments over three years Year of adopson refers to year in which nasonal program is inisated Exclude countries in which cholera vaccinason is not very cost- effecsve according to the WHO criterion based on programs targeted to children 1-14 years of age 10

11 Projected adopson sequence for 33 endemic countries 11

12 How can cholera vaccinason be targeted in the 33 included countries? Large Target Urban slums & rural areas without improved water supply (Total population = 658 million) Children 1-14 years old (233 million) All ages 1 year & older (637 million) Option 1 Option 2 Small Target 50% of population in urban slums and rural areas without improved water (Total population = 316 million) Children 1-14 years old (113 million) All ages 1 year & older (306 million) Option 3 Option 4 Bangladesh has a country-specific targeting strategy. Thus, the Small Target population is not exactly 50% of the Large Target. 12

13 What is the impact on disease burden? Impact of vaccinason depends on adopson schedule, targesng strategy, and country- specific coverage rate Assumed 80% of reported measles vaccine coverage for age % of MCV for age 15+ Campaigns are phased in over 3 yrs. and repeated every 3 yrs. Impact essmate is based on a dual transmission dynamic model constructed from data from Bangladesh Cholera spread via contaminated water and direct contact with infected persons Assume use of whole cell OCV without B- subunit (Shanchol or morc- Vax) 13

14 Cumula?ve cases prevented (millions) Projected cumulasve cases and deaths prevented Small target 1-14 Small target CumulaSve cases prevented CumulaSve deaths prevented Cumula?ve deaths prevented (millions) Cumula?ve cases prevented (millions) CumulaSve cases prevented CumulaSve deaths prevented Cumula?ve deaths prevented (millions) Cumula?ve cases prevented (millions) CumulaSve cases prevented Large target 1-14 Large target Cumula?ve deaths prevented (millions) CumulaSve deaths prevented Cumula?ve cases prevented (millions) CumulaSve cases prevented Cumula?ve deaths prevented (millions) CumulaSve deaths prevented

15 What is the projected vaccine demand? 350 Annual poten?al demand (million doses) 300 Poten?al demand (million doses) Small Target, children 1-14 years Small Target, all persons 1 year and above Large Target, children 1-14 years Large Target, all persons 1 year and above

16 Cost and storage assumpsons for OCV (Shanchol and morc- Vax) Vaccine price used current price of $1.85 per dose, and assumed reducson of 20% over a 20- year period Vaccine wastage of 5% DuraSon of protecson 3 years (campaigns every three years) Freight, insurance, carriage (15% of price) Service delivery: $0.60 (2006 WHO immunizason cossng guidelines for campaigns) Total cost per dose administered = $2.73 (decreasing to $2.27 on average over period) Cold chain storage requirements 25.5 cm 3 per dose/51 cm 3 per person Ongoing efforts to decrease size 16

17 What would be the annual program costs? Vaccine purchase and delivery cost (million US$) $800 $700 $600 $500 $400 $300 $200 $100 $ Small Target, children 1-14 years Large Target, children 1-14 years Small Target, all persons 1 year and above Large Target, all persons 1 year and above

18 Will vaccinason be cost- effecsve? 4,000 3,500 Cost per DALY averted by WHO region Cost effecsve US$ ,000 2,500 2,000 1,500 1, Very cost effecsve ,471 1, With herd Without herd With herd Without herd With herd Without herd AFR EMR SEAR Threshold for Very cost- effecsve is the weighted avg. regional GDP per capita. Threshold for Cost- effecsve is 3x weighted avg. regional GDP per capita.

19 All scenarios require capacity expansion Doses (millions) Doses (millions) Small Target for children aged 1-14 years Large Target for children aged 1-14 years Projected demand Doses (millions) Doses (millions) Small Target for all persons aged 1+years Large Target for all persons aged 1+ years Total planned capacity

20 Is a cholera vaccine reserve/stockpile a potensal opson? Demonstrated success of stockpiles for meningococcal and yellow fever vaccines Vaccine reserves/stockpiles can be used for reacsve vaccinason or preempsve vaccinason (either in humanitarian emergencies or for high- risk endemic populasons) The stockpile could lead to expanded use of cholera vaccines Spur efforts to improve cholera surveillance Provide valuable experience in deploying cholera vaccines Verify demand for vaccines and demonstrate impact under real world condisons MoSvate donors and manufacturers alike to invest in cholera vaccines and producson capacity 20

21 Es?ma?on of the annual number of people at risk of epidemic cholera (an upper limit of demand) WHO region Annual number of cases (data from ) Minimum Maximum Mean AXack rate = 5/1000 Risk Popula?on AXack rate = 10/1000 AXack rate = 20/1000 AFR 32, ,000 98,000 20,000,000 9,800,000 4,900,000 SEAR 5,100 81,000 18,000 3,600,000 1,800, ,000 EMR 1,200 60,000 11,000 2,200,000 1,100, ,000 WPR ,000 1, , ,000 50,000 Total 39, , ,000 26,000,000 13,000,000 6,500,000 2 doses required per person vaccinated 21

22 Plausible trajectory for creason of a cholera vaccine stockpile Number of doses (millions) Total cost (price + delivery) in million USD No. of doses EsSmated total cost 22

23 Vaccine stockpile: use in endemic populasons- Small Target age 1-14 yrs. No. of doses (millions) Projected demand Proposed stockpile size 23

24 Conclusions The global investment case provides evidence supporsng the feasible introducson of OCVs for control of endemic cholera Burden of disease is high in South Asia and Africa New vaccines are lower in cost and do not require buffer The introducson of OCVs would be very cost- effecsve, especially programs targesng children A relasvely modest- sized stockpile would be inexpensive, but would ssll be large enough to be of value A stockpile could also be a gateway to sustainable cholera vaccine introducson Steady predictable demand would mosvate investment in vaccine capacity and demonstrate the value of cholera vaccinason to donors, helping to ensure adequate vaccine supply 24

25 Acknowledgements Cholera investment case team Cholera investment case Advisory Commiwee Country partners in Bangladesh and Uganda SIDA and BMGF for funding Shantha/Sanofi, VaBiotech, and Crucell 25

26 QuesSons? 26