Origin and global spread of the seventh Cholera pandemic

Hello, everyone. In this video, we will use Microreact to investigate the epidemiology of the seventh cholera epidemic in Africa. We will use the phylogeny and metadata of over 1,000 Vibrio cholerae isolates, collected during 50 years across 45 African countries. First, on the Tree panel, click on the Show Controls button to select the hierarchical layout. Select Transmission Event under the list Colour By to display the colours of transmission events. Know that there are 12 transmission events in total, highlighted on the tree. Each of them corresponds to a monophyletic clade made up of Vibrio cholerae samples collected from the same African region. We will investigate what is the origin of these transmission events.

Second, search for the two samples from Ethiopia using the search box at the top of your screen. Select country of isolation under Label By to show what country samples came from. Zoom in to take a closer look at clade T3 and take some time to identify the internal node that represents the common ancestor of all T3 isolates. Next, use the tree to identify closely related isolates. You will note that isolates from Ethiopia are closely related to isolates from the same year from Jordan and Israel, which suggests an importation of this sublineage from the Middle East into Ethiopia. Now, then we’ll click on a blank space to highlight all isolates and zoom out to visualise the whole tree again.

Now, we will investigate the source of the Latin America epidemic in the ’90s, labelled as Transmission Event DG. First, click on DG on the Legend panel to highlight all isolates from this sublineage. Zoom in to identify the internal node that defines these clades. If you click on it, you will highlight only DG isolates on all three panels. You will notice that most isolates were collected in Central and South American countries in the ’90s. Now, use the tree to identify closely related isolates to this clade, that is descendants of more ancestral nodes. Based on the location and collection dates of neighbouring isolates, the investigators concluded that the Latin American epidemic most likely originated from West Africa.

The investigators also noted a recurrent pattern of transmission for cholera epidemics in Africa. Several sublineages of the seventh pandemic, labelled as different transmission events, were repeatedly introduced into two main regions, either to West Africa or to East and Southern Africa. Epidemic waves then propagated regionally, in some instances spreading to central Africa, over periods of a few years to 28 years. Examples of importations to East and Southern Africa include transmission events T3, T4, T5, T6, T8, T10, and T11. Examples of importations from Asia to West Africa include sublineages T7, T9, and T12. In summary, the authors found that multiple sublineages originated from South or East Asia and were circulating in the Middle East before being imported into West or East Africa.

Next, we will use Microreact to visualise what sublineages carry the SXTR371 genomic island and the temporal spread of these. Remember from the previous step that this genomic island carries multiple AMR genes. Colour-code samples by transmission event and show the SXTR371 label on the tree under Label By. Type in ICEV in the search box at the top of your screen. This will highlight what samples carry this genomic island. You should be able to distinguish what lineages carry the genomic island, at the left-hand side of the tree, from those that do not, at the right-hand side of the tree. A close inspection will reveal that sublineages 8, 9, 10, 11, and 12 all carry this genomic island.

A closer look shows how the genomic island has remained very stable within these lineages, that is it has rarely been lost. This is characteristic of chromosomal integrated conjugated elements which, once integrated into the chromosome, are inherited vertically. We will now visualise the temporal and geographical spread of the different sublineages. First, make sure you can view the whole tree and the search box is empty so that all isolates are shown. You should now be able to see the 12 transmission events highlighted on the tree and map with different colours. Open the Timeline panel, select Quarter as the chosen time frame, and set the play speed to one quarter per second.

This will create a movie where isolates will be shown on all panels according to their date of isolation. Lastly, click on the Play timeline button.

The first isolates to appear correspond to the earliest and more ancestral isolates collected from Central and Southeast Asia in the ’60s. There is the origin of the seventh pandemic lineage. After this, isolates from the T1 sublineage appear in the ’70s, mostly clustered in North Africa, West Africa, and Europe. This sublineage continues to spread throughout Southern Africa during the ’70s. Isolates from the Latin American epidemic, shown in red, emerge in the ’90s. The multi-drug-resistant sublineages in Africa carrying the genomic island, that is T8, 9, and 10, also started emerging in the ’90s, followed by sublineages T11 and T12, all five accounting for most of the Vibrio cholerae cases sampled in the last 20 years.

Altogether, this data shows that the recent increase in cases of multi-drug-resistant Vibrio cholerae in Africa has been largely driven by the importation of already resistant sublineages from South Asia. That is attributable to sublineages T8 to T12, as opposed to the independent acquisition of resistance within Africa.