Project Name: Cholera Genomics Consortium II
Grant Amount: USD 4,995,205
Grant Duration: 01/12/2022-31/12/2025
Introduction
Every year, approximately 4 million cases and 143,000 deaths, due to cholera, are recorded globally, of which at least 54% are from Africa. In 2021, the average preliminary Case Fatality Rate (CFR) was 2.8%. Cholera is also one of the pathogens prioritized by the Africa CDC for preparedness and response.
Cholera has been largely eliminated from industrialized countries through treatment of domestic water and sewage, and good living environment. However, it remains a serious public health problem in some parts of the world including Africa, causing illness and death. Deployment of an Oral Cholera Vaccine (OCV) is a key intervention that can prevent and control cholera outbreaks. Other important interventions include improved water, sanitation, and hygiene (WASH) activities and cholera genomic epidemiological surveillance in endemic areas. A Global Roadmap to 2030 operationalizes the new global strategy for cholera control at the country level and provides a concrete path toward a world in which cholera is no longer a threat to public health.
By implementing the strategy between now and 2030, the Global Task Force on Cholera Control (GTFCC) partners are supporting countries to reduce cholera deaths by at least 90 percent. In 2021, GTFCC reported twenty-one countries with cholera outbreaks globally. The roadmap is concentrating on controlling the disease at country level, but a critical element for outbreak prevention is establishing an efficient mechanism that ensures routine monitoring and identifying sources of Vibrio Cholerae. During COVID-19 pandemic, Whole-Genome Sequencing (WGS) proved to be an essential tool for infectious disease surveillance and outbreak investigations. WGS coupled with epidemiological and environmental investigations delivers ultimate resolution for detecting and analyzing transmission routes and tracing sources of outbreaks as well as assessing pathogen’s immune escape properties, virulence and antimicrobial resistance determinants. WGS of Vibrio cholerae is now providing unprecedented insights into where cholera strains emerge and then spread to other areas. It is time to integrate these developments into routine public health measures especially in outbreak prone areas of Africa. However, cholera genomic surveillance remains largely unutilized for this purpose in these regions.
A single consortium with a steering committee composed of Africa Centers for Disease Control and Prevention (Africa CDC), Johns Hopkins University (JHU), and Bill & Melinda Gates Foundation (BMGF will leverage on existing laboratories and epidemiologists in the five selected African countries (Nigeria, Democratic Republic of the Congo (DRC), Mozambique, Cameroon, and Uganda) with the goal of utilizing cholera genomic data for public health decision making and improving the understanding of the molecular epidemiology of cholera in Africa. A primary focus of the consortium will be on building sustainable capacity for Vibrio cholerae genomics in each of the countries, leveraging on existing capacities and networks through coordination, training, mentoring, technical and logistics support from JHU and Africa CDC. Capacity will also be built through training, exchange of knowledge and skills between the participating African countries. At the end of this project, the countries in the consortium will be fully capable of generating standardized metadata and sequencing data for public health decision making using an end-to-end genomic surveillance framework which can be replicated in other African countries. Furthermore, the consortium anticipates that these genomic skills will be used to further understand bacterial genomics of other important pathogens, e.g., Salmonella Typhi, Klebsiella pneumoniae and Shigella species. The pilot will be implemented in five selected Africa PGI supported countries: Uganda, Cameroon, Nigeria, Democratic Republic of the Congo (DRC), and Mozambique.
The primary outcome of this investment from BMGF is to build genomic-informed management of Vibrio cholerae in the areas most affected by cholera through a coordinated genomic surveillance mechanism. The cholera genomic consortium in Africa will document multi-country lessons learned to improve future technical collaboration & coordination as well as guidance for oral cholera vaccine (OCV) deployment in cholera endemic areas.
During the project period, the Africa CDC through PGI in collaboration with APHF, JHU and Member States made significant progress in the project implementation. These include:
- Advocacy for enhanced cholera surveillance in Africa
The CholGEN project has further allowed the Africa PGI team to advocate for rapid, effective and enhanced Cholera surveillance and emergency response in Africa. The advocacy continues within the Africa CDC, at national, regional and global levels. For example:
The CholGEN project was presented to advocate for the need to enhance cholera genomic surveillance to track cross-border cholera transmission at the first “High-Level Emergency Ministerial Meeting on Cholera Epidemics and Climate-Related Public Health Emergencies” held in Lilongwe, Malawi from 9th – 10th March 2023. Ministers and senior technical experts from Angola, Botswana, Comoros, Congo, Eswatini, Lesotho, Malawi, Mozambique, Namibia, Tanzania, Zambia and Zimbabwe participated in the meeting.
The project team is actively participating in the development of Africa CDC’s strategy for the continental Cholera response plan.
The project team participated in the Malawi/Mozambique cross border cholera surveillance strategy meeting held in Malawi from 24-28 July 2023.
- Retrospective Cholera Genomic Surveillance in Africa
Leveraging stored Vibrio cholerae isolates to build genomic surveillance capacity was the primary objective of the project for 2023 and Q1 of 2024. for the implementation of cholera genomic epidemiology in Nigeria, DRC, Mozambique, Cameroon, and Uganda.
- Cholera WGS across the consortium:
The CholGen and other Africa PGI projects continue to support sequencing of stored cholera isolates at regional sequencing hubs and locally at all the participating laboratories. A total of 382 isolates were sequenced and genomes sequences were shared with the Africa CDC.
- Technical assessment and supervision visit to participating Member States.
The visit encompassed a comprehensive review of the CholGen Project’s activities, both retrospective and prospective, with a focus on aspects such as sample collection, processing, identification, and storage.
NCDC in Nigeria – Demonstrated how cholera samples are collected, processed, identified, stored, and later sequenced. Their process is well elaborate, and this ensures over 98% recovery of archived isolates. Bacteriology lab informed the Africa CDC that they use 20% skimmed milk and 20% glycerol to store cholera isolates.
CPHL – Uganda, INRB – DRC, and INS – Mozambique – Demonstrated how cholera samples are collected, processed, identified, and stored. Their process is elaborate; however, they are struggling to recover the archived cholera isolates, and their recovery rate is below 50%. To assist these labs, Africa CDC connected them with NCDC Nigeria and took them through the entire recovery process.
NPHL – Cameroon – Demonstrated how cholera samples are collected, processed, identified, and stored. Their process is elaborate; however, their recovery rate is at 7% of archived isolates. We discovered that the problem was at the bacteriology lab. It was noted that there were challenges in the processing. Africa CDC technical team recommended the following corrective measures. Similarly, to assist NPHL, Africa CDC connected them with NCDC Nigeria who will take them through the entire recovery process.
In addition to the on-site assessments, the Africa CDC technical team delved into the review of bioinformatics infrastructure and capacity at the respective institutions. To enhance the project’s analytical capabilities, Terra bioinformatics pipeline was introduced, ensuring that the participating countries have the necessary tools and resources for effective genomic analysis of cholera isolates. This comprehensive approach reflects the commitment of the CholGen project to not only generate valuable genomic data but also to strengthen the capacity of the participating countries in bioinformatics and genomic analysis.
- Supporting the Surveillance Working Group
The Surveillance Working Group of the CholGen Project conducted an extensive review of cholera surveillance systems in the participating member states. The aim was to assess strengths, identify gaps, and propose opportunities for enhancement in each country’s surveillance system.
