Cholera

Cholera is an acute diarrhoeal infection, caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Cholera remains a global threat to public health and an indicator of inequity and lack of social development

Key Factors
  • Cholera is an acute diarrhoeal disease that can kill within hours if left untreated.
  • Researchers have estimated that each year there are 1.3 million to 4.0 million cases of cholera, and 21,000 to 143,000 deaths worldwide due to cholera.
  • Up to 80% of cases can be successfully treated with oral rehydration solution (ORS).
  • Severe cases will need rapid treatment with intravenous fluids and antibiotics.
  • Provision of safe water and sanitation is critical to control the transmission of cholera and other waterborne diseases.
  • Safe oral cholera vaccines should be used in conjunction with improvements in water and sanitation to control cholera outbreaks and for prevention in areas known to be high risk for cholera.
  • A global strategy on cholera control, with a target to reduce cholera deaths by 90%, was launched in 2017 by WHO.

Fig. 1 Cholera bacteria under an electron microscope

Cholera poses a severe challenge to a number of low and middle income countries…
  • Cholera is an acute diarrhoeal disease that can kill within hours if left untreated.
  • Cholera affects at least 47 countries across the globe, resulting in an estimated 2.9 million cases and ~ 95,000 deaths / year.
  • ~2 billion people, without access to safe water, are potentially at risk for Cholera globally.
  • 89 million people live in Cholera "high risk" areas in Africa alone.
  • Cost of economic burden is estimated at US $2B/ year due to health care cost and lost productivity.
  • OCV to be used in conjunction with improvement in water & sanitation to control cholera.
  • Global Task Force on Cholera Control (GTFCC) will support countries to reduce Cholera deaths by 90% by 2030.

Cholera Demand
  • Gavi demand for OCV increased from ~0.2 million doses (md) in 2013 to >13 md in 2017. The travellers and military market is estimated at 1.3 md/year.
  • The roadmap focuses on the countries that are considered to be at highest risk for cholera, and on India.
  • Stockpile for outbreak response is expected to remain around 5 md between 2019 and 2023 and to stabilize at 2.5 md from 2028
  • Volume required for endemic use is expected to increase to approximately 18 md in 2018, 31 md in 2019, 64 md in 2021, reaching approximately 74 md in 2022, and may stabilize at about 65-70 md from 2025-2026.
  • Bangladesh is expected to represent an average of 36% of the Gavi39 demand during 2018-2028.
  • Demand for India could reach up to 20 md within 3 years and 80 md within 6 years.
  • Beyond Gavi39 and India, other countries may require up to 4.3 md in 2019, 12 md in 2023, and 7 md in 2028.
  • Travellers and military market is expected to increase from about 1.3 md to 2 md/year over the next ten years.

Source: Gavi Cholera Supply and Procurement Roadmap, December 2018

PROBLEM STATEMENT

Current prequalified vaccines effective but complex to manufacture:

  • 3 or 4 different strains
  • Two different inactivation methods

APPROACH

Single vaccine strain (Hikojima) incorporating desirable characteristics of the current Cholera vaccine:

  • Ogawa and Inaba dual expression
  • Single fermentation run
  • One inactivation method
  • Efficient process results in lower COGs
Science behind Hillchol™

Single vaccine strain (Hikojima) incorporating desirable characteristics of the current Cholera vaccine:

  • wbeT gene mutated and inactive in Inaba phenotype
  • Fully functional wbeT gene
  • Partially functional wbeT gene

Co-expression of Inaba and Ogawa serotype antigens
However, no stable Hikojima strains exist in nature

PLOS ONE, November 2014 | Volume 9 | Issue 11 | e108521