Cholera in Yemen

The cholera outbreak in Yemen is considered one of the largest in proportion and most protracted in duration ever recorded in recent history. The number of cases reported in the country since the outbreak started in 2016 has now surpassed 2.5 million cases and over 4,000 deaths.

When the disease first appeared in October 2016, there was interest in knowing where the disease originated from before it first set a foothold in the country. At that time, outbreaks of cholera were reported in Iraq and other countries in the East Mediterranean region while small-scale outbreaks in East African countries such as Kenya, Tanzania, and Uganda were also being reported.

Genomic epidemiology was identified as the most relevant tool to address this important public health question. As Yemen did not have genomic sequencing capacity, Vibrio cholerae isolates from Yemen and their genomic DNA extracts were sent to collaborating partners including the Pasteur Institute of Paris and the Wellcome Sanger Institute for sequencing and genomic analysis.

This analysis established that the sub-lineage of Vibrio cholerae that caused the outbreak in Yemen is closely related to sub-lineages responsible for outbreaks of cholera in East African countries such as Kenya, Tanzania, and Uganda. Even though genomic data did not present enough evidence for a precise route of transmission, it indicated that population movement may have been the route by which the disease arrived in Yemen. From there, it spread in large proportions within the country owing to the scarcity of clean water and the breakdown of water, sanitation and hygiene (WASH) infrastructure, including the sewage systems, as a direct consequence of the war.

As the outbreak continued, in late 2018, the bacteriology laboratories in Yemen reported Vibrio cholerae isolates that were becoming resistant to key antibiotics used for the treatment of the disease. Antibiotic therapy is not the mainstay for the treatment of cholera. However, antibiotics reduce the duration of illness and volumes of stool – both of which are important determinants in the transmission of the disease. There was a need to know whether the multidrug resistance pattern reported from the bacteriology laboratories was present at the genome level and to understand the molecular basis driving the rapid spread of the multidrug resistance clones in a short period of time.

A total of 260 Vibrio Cholerae isolates collected from Yemen in 2018/19 were successfully sequenced in partner institutions. Genomic analysis revealed the timelines and the mechanism behind the spread of multidrug-resistant strains. It was shown that a minority clone of Vibrio cholerae – present in 6/89 (6.7%) of the sequenced isolates first emerged in late 2018. This clone had acquired an IncC-type plasmid carrying a multi-drug resistance (MDR) transposon that could confer resistance to a number of antibiotics useful for the treatment of cholera. By 2019, this minority clone rose to dominance and was present in 151/151 (100%) of sequenced isolates from 2019. Isolates carrying this plasmid were essentially resistant to key antibiotics that were being used for treatment in Yemen. After this report, the clinical guidelines for treatment with antibiotics were revised and antibiotics such as azithromycin and trimethoprim-sulfamethoxazole were no longer prescribed for patient treatment. Instead, doxycycline was then used to treat all cholera patients in Yemen. This work is reported in an article currently under peer review and a preprint is already accessible.

Genomic surveillance was also crucial in confirming phenotypic characteristics of the strains, describing the spatiotemporal distribution of the strain causing annual successive waves of cases, and revealing genomic variation of V. cholerae strains within Yemen. This showed that the epidemic strain that spread globally co-occurred with diverse endemic strains, and exchanged genetic material with them, which is the likely mechanism for the emergence of the MDR strain.

In summary, the experience of cholera and other infectious disease outbreaks, such as COVID-19 in Yemen, has shown that genomic surveillance/epidemiology is an indispensable tool in tackling disease outbreaks and in getting better outcomes from all the public health interventions, such as diagnostics, therapeutics, and control/prevention tools, aimed at tackling disease outbreaks.