The Black Death has claimed 165 lives on the Africa island since the outbreak which has infected around 2,000 people.
Infection and immunity expert Dr Matthew Avison said: “This disease is extremely rare, it doesn’t get exposed to antibiotics that often.
“That means it’s more resistant to antibiotics and the risk of death is higher.”
The airborne disease has devastated Madagascar as it spreads quickly through the population.
Dr Avison, of the University of Bristol, has called on the authorities to ensure antibiotics are handed out quickly in order to increase the chances of containing the outbreak.
Claiming that if they act fast enough the Black Death can “still be treated”.
However, a failure to act quickly could lead to the worst outbreak in 50 years with a risk of it spreading to other continents, Dr Avison warned.
Europe and the United States could be in the firing line if the disease is not contained.
Dr Avison said: “It’s starting to be a big problem.
“The worrying thing is it’s going to spread to other countries if not properly contained. There is evidence that is happening already.
“It’s will probably get worse before it gets better.”
The World Health Organisation (WHO) have issued a warning about the possibility of the infection spreading.
Currently, 10 countries have been put on alert about the virus, with Malawi, South Africa, Ethiopia, Kenya, Mozambique, Seychelles, Tanzania, La Reunion, Mauritius and Comoros Islands all being told to prepare.
Scientists also believe the disease, which can kill in 24 hours, could become untreatable in the future if the virus mutates.
Dr Avison said this is unlikely to happen anytime soon as old antibiotics developed decades ago can still cure the disease.
He said the problem is “access to those” antibiotics in countries with poor health infrastructure.
This current outbreak is “different” to those seen before WHO claimed it needs £3million to stop the black death’s spread.
An update from the WHO said: “While progress has been made to control the outbreak of plague in Madagascar, the possibility of future flare-ups cannot be ruled out.
“Notwithstanding the financial support and contributions from partners, WHO urgently requires an additional $4million (£3m) to sustain response operations in the next three months of the plague outbreak in Madagascar.
“The funding is needed to interrupt ongoing transmission, provide care for those affected by the disease, reduce the risk of international spread and provide effective coordination and operations support.”
All schools in the country had been disinfected and 8,000 community leaders had been trained to spot signs of the disease, the WHO said.
They warned the majority of regions in Madagascar, 14 of 22, had been hit by the outbreak.