Infections are caused when disease-causing agents enter the body and multiply. Cholera is one of these, for which it was estimated that globally there were 1.3 – 4 million cases in 2017 that resulted in 143,000 deaths. This is the consequence of the seventh cholera pandemic that originated in South Asia in 1961 and spread throughout the globe over the course of the next 50 years. However, little is known about its propagation routes in Africa, the country most affected by this pandemic.
Professor Dougan and his colleagues have reconstructed the spread of cholera across the continent by analysing the genomes of 1070 cholera isolates. Such work helps to determine the factors that are important in the spread of the disease and allows us to gauge the impact of future interventions.
By mapping their data onto historical records of cholera outbreaks these scientists found that resurgence of cholera in the 1970’s was the result of two strains, one in West Africa, and another in East Africa. The West African strain first appeared between July and September 1970 and was likely to have come from Asia. Countries such as Angola saw infection despite being over 1000 km from the closest country with cholera at the time and this then led to an outbreak in Mozambique in 1973. The link between these quite distant countries may have been a Portuguese decolonisation war that was occurring at the time, which is then likely to have resulted in a Portuguese outbreak that occurred a year later. Subsequent reintroductions led to new outbreaks extending over many years up to 2003. The East African strain also appeared in 1970, but was more closely related to strains from the Middle East, suggesting that it had originated there. This strain was associated with several outbreaks over the next 40 years, leading to 125,000 cases of cholera in South Africa in 2001-2002, and 98,000 cases in Zimbabwe in 2008-2009, . Even these strains had originated in Asia, but some had circulated in the Middle East before moving into the East African region. Many of the outbreaks could be linked to large migrations resulting from war or from religious practices such as pilgrimage.
Antibiotic resistance is a growing global concern and as it represents a serious global health risk it has been the focus of much recent attention. The study by Professor Dougan and his colleagues was also able to discover the emergence of antibiotic resistance in their cholera strains. They found that African isolates became increasingly resistant over time. While the earliest of these were recovered in the early 1980’s, only resistant forms have been collected since 2000. The results showed that this spread of resistance is likely to have occurred by determinants that were already in these disease-causing organisms as they spread, rather than independent local acquisitions of resistance. In other words, the bacteria already contained the genetic information they needed to overcome antibiotics and its emergence was likely to result from human intervention. There are several examples of these, such as a Tanzanian strain that coincides with the use of 1.79 metric tons of tetracycline used by the Tanzanian Ministry of Health to control an outbreak of a susceptible strain. Five months later, 76% of isolates in the region were resistant to tetracycline and other antibiotics.
These studies show how it is possible to use modern scientific methods to monitor the spread of diseases, even long after outbreak events. The genomic data were consistent with events that were controlled by human activities, and demonstrated that these are more important than climatic or environmental considerations. As such, they highlight that the long-term spread and maintenance of cholera in Africa is largely a consequence of direct, human to human transfer, or indirect infection by water polluted with human faeces. Such large-scale scientific interpretations over long time scales have an enormous impact on our ability to govern the continued spread of this disease and anticipate future outbreaks.
Professor Gordon Dougan