Two confirmed cases this week of Pneumonic plague in China have local and international health agencies on high alert. A middle-aged couple are being treated in Beijing for the most severe form of the infection that has afflicted humanity since the Bronze Age. 

The bacterium Yersinia pestis can cause three distinct disease manifestations dependent on the route of infection. With Bubonic plague, attributed to catastrophic Black Death pandemic of the 14th century, the bacterium enters the body via the skin, normally through a flea bite. In the Septicemic form, as the name suggests, the blood is infected. With this most recent case of Pneumonic plague, the severe lung infection has up to 100% mortality rate if left untreated. Luckily, early diagnosis and treatment with common antibiotics such as streptomycin and doxycycline, is highly effective.

These new cases are still however, a cause for concern as this variant does not need an infected animal or flea to spread, only inhalation of droplets from infected individuals. Bubonic plague is not just a disease of the past, with thousands of cases occurring around the globe each year. The Black Death of the 1300s killed around 75 million in Europe and altered the genomes of the population, resulting in increased resistance to HIV and heightened immune responses.

The genetics of Y. pestis and its subtypes have been extensively studied to find potential drug targets. Currently there are no vaccines for the plague. This is due to a combination of poor efficacy of previous formulations and the natural diversity of antigens carried by the bacterium. F1 and V antigens are anti-phagocytic factors produced by the bacteria in the body and within white blood cells. Natural and artificial immunity through vaccination comes from antibodies present in the body which target F1 and V antigens for neutralisation. However, bacteria without F1 have been found thriving and V antigens are variable enough to diminish vaccine efficiency.

One potential target for prevention could be in the plasmids the gram-negative bacterium carries that contribute to its virulence. One plasmid, pFra, facilitates the transmission by fleas, the classic transmission method. Another, pPla activates an enzyme, plasmin, that degrades blood plasma proteins in humans. pPla is an important virulence factor for overwhelming the lungs in pneumonic plague, allowing the bacteria to replicate rapidly in the airways. Studies have shown this plasmid controls the development of primary plague and its inhibition led to increased survival in affected animals.

This offers an exciting therapeutic option for this deadly disease which is still affecting the global population. Meanwhile international health agencies remain on high alert to combat and prevent outbreaks of this historic disease.

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