Dr. Philip McMillan,  John McMillan

On a Friday in Siberia, a 28-year-old woman who worked at the Siberian Plague Institute died of pneumonia. Around 200 people were placed in quarantine. Reuters reported that no plague cases had been detected, and the origin of her illness has still not been established. Those are the facts, and there are not many of them. Yet the word plague carries a weight that few other words in medicine can match, and within days it had found its way back into the headlines.

Dr. McMillan, a British researcher and clinician, is not inclined to take the official account at face value. He notes that the Russian authorities have not explained how the woman fell ill, and he places her death in a longer run of outbreak scares: bird flu, Nipah virus, hantavirus, and now plague. Is the sequence a coincidence, he asks, or a pattern worth watching? It is a reasonable question, though a single unexplained death cannot answer it. What can be answered with some confidence is a different set of questions. What is plague? How does it overpower the body? And why, in an age of antibiotics, is it usually curable?

Three Pandemics Before Antibiotics

To understand why the word still frightens people, it helps to look back. Before antibiotics, plague swept across the world three times. The first pandemic began in 541 and is estimated to have killed between 25 and 50 million people. The second, the Black Death of 1347 to 1353, killed somewhere between 75 and 200 million, and Europe lost 30 to 50 percent of its population in the space of six years. The third, concentrated mainly in India and China, claimed another 12 to 15 million lives. Historians work from patchy records, so the ranges are wide, but even the lowest estimates describe a catastrophe on a scale that is hard to hold in the mind.

“This is a beast of a disease,” Dr. McMillan says. “You don’t want to be messing around with this.”

Fleas, Rodents and Droplets

The culprit is a bacterium, Yersinia pestis, and it reaches people in two main ways. Bubonic plague, the classic form, travels by flea. A flea feeds on an infected rodent, picks up the bacteria, and passes them on when it later bites a person. Pneumonic plague settles in the lungs. It is harder to catch than a cold or the flu, but it can pass from one person to another through close contact with respiratory droplets, and that distinction carries real weight. A disease that needs a flea to move can be contained by controlling rodents and their fleas. A disease that moves directly between people is a far more difficult thing to stop.

A Trojan Horse in the Immune System

The most remarkable part of the story begins after the bite. When bacteria enter the body, the immune system dispatches macrophages, large white blood cells whose job is to swallow invaders and digest them. Y. pestis is swallowed readily enough. In some people, though, it is never digested. Tucked inside the very cell sent to destroy it, the bacterium is hidden from the rest of the immune system and shielded from being broken down, and there it begins to multiply.

Macrophages do not stay put. They migrate to the lymph nodes, the filtering stations of the immune system, and the infected cells carry their passengers with them. There the bacteria keep replicating until the nodes swell into the painful, tender lumps known as buboes. For the patient, this usually arrives with fever and chills.

Then comes the cruelest twist. Having used the macrophage as a nursery, the bacteria destroy it and burst out wrapped in a protective capsule, a coating that prevents other macrophages and immune cells from engulfing them. The defenders arrive and find nothing they can grab hold of. Left untreated, the infection can escape the lymph nodes and spread through the blood, and it is this collapse of the body’s defenses, in Dr. McMillan’s account, that explains the staggering death tolls of the pre-antibiotic era.

The Good News: A Treatable Infection

So if the bacterium is this cunning, why is plague not a constant threat today? The answer is antibiotics. Plague responds to simple, inexpensive drugs, primarily doxycycline, which Dr. McMillan puts at 97 percent effective. Many people never become seriously ill at all, because a healthy macrophage can often destroy the bacteria on its own, or with an assist from antibiotics.

Dr. McMillan’s concern lies in a pair of hypothetical scenarios. If a strain were ever altered to resist standard antibiotics like doxycycline, the safety net would fray. If it were altered to spread more readily between people, shifting the balance toward pneumonic plague, the problem would grow larger still. He ties both possibilities to gain-of-function research, the laboratory practice of modifying pathogens in order to study them. It is a worry rather than a finding. Nothing reported about the Siberian case points to such a scenario, and Dr. McMillan acknowledges that the episode may turn out to be nothing at all.

An Opinion About Tired Macrophages

At this point Dr. McMillan moves from established biology into hypothesis, and the shift deserves to be marked clearly. His research group has previously linked macrophages to severe COVID and to long COVID, and he believes the same cells shape the unusual patterns that follow repeated reinfection. After years of recurring COVID exposure, he proposes, many people’s macrophages may be exhausted, depleted or overactivated. In that state they might allow bacteria like Y. pestis to replicate more freely, spill into the bloodstream and cause more extensive disease. He is explicit that this is speculation. “This is just my opinion,” he says, “there is a very unique post-pandemic risk.”

What supports the idea? Dr. McMillan has been following UK Hospital Episode Statistics across a decade, from 2016 to 2026. In the most recent year, the category B99, “other unspecified infectious diseases,” showed the largest rise. He reads this as evidence of immune dysregulation, which he distinguishes from immune suppression: an immune system that responds too weakly when an infection arrives, yet overreacts when none is present, a pattern he links to the chronic symptoms of long COVID.

The observation is intriguing, but it needs careful handling. A rise in a catch-all hospital category can have many causes, including changes in testing, shifts in how cases are coded, and an aging population. On its own, it cannot show that anyone’s macrophages are exhausted, and it says nothing directly about plague. The hypothesis is a question worth testing, not a conclusion to act upon.

What Readers Can Take Away

Set the headlines aside and the picture becomes steadier. Plague is ancient, serious and well understood. Scientists know the organism, the routes by which it spreads and the drugs that defeat it, and most people who are treated promptly recover. The genuine unknowns are narrower than the alarm suggests: how the Siberian death occurred, and whether repeated COVID infections alter the way the immune system handles other threats.

On that second question, Dr. McMillan offers practical advice: reduce the chances of respiratory viruses breaking through the upper airway, a theme he develops in his recent book on nitric oxide. One need not accept every part of his wider argument to see the sense in it. An immune system that is not fighting one infection after another has more in reserve when the next one comes.

Plague, in the end, is the story of a bacterium that turns the immune system’s own soldiers into hiding places. Medicine has the tools to counter it. The harder task is keeping enough curiosity, and enough calm, to tell a headline from a genuine threat.