Multiple barriers to ending Madagascar’s plague outbreak

In Madagascar more than 30 people have died from the plague in the past few weeks. Several hundred more are infected with the disease, and health authorities on the island are struggling to deal with the rapidly spreading outbreak.

Once a scourge across Europe and Asia, the plague – caused by a species of bacteria called Yersina pestis – is today largely absent from its former territories. In Madagascar, however, it remains endemic, and cases are recorded each year, although rarely in the numbers currently being experienced.

According to the US centres for Disease Control (CDC), around the world there are between 1000 and 2000 plague cases recorded every year. From 2010 to 2015, Madagascar accounted for 82% of them.

Papers published this year have helped to explain why the island’s plague problem is so stubborn and persistent. Other research lends hope that, at least in the medium term, the disease can be defeated.

In September this year, a team led by David Wagner from the Pathogen and Microbiome Institute of the Northern Arizona University, US, took 773 samples of Y. pestis from Madagascar and used genome sequencing to identify 31 separate strains of the bacteria.

These were correlated against location information, with the result that the scientists were able to classify the strains into 18 geographically and genetically distinct subpopulations. These subpopulations have persisted for at least two decades.

Wagner and his team found that the geographically distinct plague groups were often carried by people from one area to another, but once transmitted seldom if ever established a new territory.

Thus, there is no single dominant strain of the bacteria on the island, which might make a useful target for any one-size-fits-all treatment. The team found that, instead, different geographic and genetic subtypes flared at different periods, causing outbreaks.

“Persistent, local transmission cycles are likely responsible for the long term maintenance of plague in Madagascar,” the team concluded.

The spread of the plague is famously facilitated by fleas, but this isn’t quite as simple – and therefore potentially susceptible to biological control – as it sounds.

For a start, Y. pestis bacteria are highly promiscuous and can use several species of fleas as distributors. Secondly, they have more than one method of getting from inside the insect to inside a person.

In January this year research from a team led by Joseph Hinnebusch of the US National Institutes of Health set out to determine the relative efficiency of two of the plague’s most common flea vectors in passing on the bacteria.

The scientists looked at fleas known as Xenopsylla cheopis and Oropsylla montana. The found that after having first contracted the bacteria by consuming the blood of an infected mammal, the insects had two methods of passing them on.

The first method can occur as soon as the next time the flea feeds, and remains possible for a week or so. The mechanism by which it happens is still unknown.

The second method occurs after Y. pestis settles into its flea host. A short while after being consumed, the bacterium migrates into the flea foregut, where it beds down and covers itself with a protective biofilm.

As numbers increase, the biofilm capsules eventually block the function of the flea’s proventricular valve – the mechanism that closes to prevent ingested blood refluxing back up into the oesophagus.

The blockage also effectively stops the flea feeding, with the result that it vomits, dislodging the bacteria and sending them into the bloodstream of whatever mammal is providing its meal.

In a paper published in the journal PLOS Neglected Tropical Diseases, Hinnebusch and his colleagues found that in both species the first soon-after-eating method of transmission was not very common, with the biofilm blockage accounting for most cases. Xenopsylla cheopis  was found to become blocked much more readily than the other species. Both, however, made very efficient vectors.

So with multiple flea species transmitting multiple subpopulations, Madagascar’s battle to contain the plague is likely to be challenging. 

There are, however, some encouraging developments. 

A team from the Israel Institute for Biological Research has been working on developing a vaccine using live Y. pestis. In a paper published in March this year in the journal Frontiers in Cellular and Infection Microbiology, the scientists reported that a trial vaccine given to mice protected them even when given a normally lethal dose of plague immediately after.

The road from successful mouse study to human clinical trials and then to mass rollout across an entire island nation is likely to be a long one, but at least the journey has been started. 

Of more immediate impact, perhaps, is the potentially life-saving use of social media. A study published in July this year and led by Omar Da’ar of the King Saud Bin Abdulaziz University for Health Sciences in Saudi Arabia examined tweeting habits of Madagascans during another, smaller, outbreak of plague in 2014.

Looking at the Twitter feed for one week in November at the height of the outbreak, the researchers found that tweets containing plague-related messages were a very efficient way for people to pass on information about the spread of cases.

The researchers concluded that “Twitter can play an important role in ongoing disease surveillance and the timely dissemination of information during public health emergencies”.

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