Dr. Philp McMillan,  John McMillan

Four years ago, a prediction circulated among those paying close attention to immune response data. Specific interventions, it was argued, would trigger a cascade of immune suppression, one that would eventually manifest as a population-level resurgence of ancient diseases. Tuberculosis sat at the top of the list.

At the time, the prediction seemed premature. The conversation around “shedding” focused on the wrong mechanism entirely: exosomal transfer of RNA through saliva, a phenomenon considered clinically insignificant. But the real concern was never about spike proteins passing between people at dinner parties. It was about something far older and far more dangerous: the possibility that weakened immune systems would lose their grip on pathogens they had spent years containing. New data from Pakistan and South Korea suggests that prediction is now arriving on schedule.

We may be witnessing the early stages of a granuloma breach, a slow-motion failure of the immune architecture that keeps latent infections locked away. The implications extend far beyond any single pathogen.

The Perfect Prison

*Mycobacterium tuberculosis* is not a bacterium the human body defeats. It’s one the body learns to live with.

TB is ancient. It has co-evolved with humans for tens of thousands of years, developing an almost perfect defense: a cell wall so sophisticated that immune cells cannot degrade it. When macrophages, the body’s front-line defenders, engulf TB bacteria, they are unable to digest their prey. The bacteria simply sit inside these cells, alive and waiting.

The immune system’s solution is architectural. Unable to destroy the invader, it builds a prison instead. This structure, called a granuloma, is a marvel of biological containment. At its center sit infected macrophages, holding bacteria they cannot kill. Surrounding them is a wall of giant cells and neutrophils. On the outer perimeter, lymphocytes stand guard. The result is a cellular fortress, a standoff that can last a lifetime.

TB functions “almost like a bacterial form of HIV, because you just can’t get rid of it,” as researcher and clinician Dr. Philip McMillan has noted. The comparison is apt. In both cases, the immune system reaches a stalemate rather than a victory. The difference is that with TB, the stalemate depends entirely on the strength of the walls.

Roughly a third of the global population carries latent tuberculosis, bacteria locked away in granulomas, causing no symptoms, posing no immediate threat. The prison holds. But prisons require guards. And the guards, it appears, are getting tired.

The Pakistan Signal

A preprint study from Pakistan offers the first direct evidence of what was predicted years ago. The research team examined immune responses in a COVID vaccinated cohort, comparing those with no prior symptomatic COVID-19 infection against those who had experienced the disease. Pakistan was an ideal setting, a high-endemic region where latent TB infection rates range from 30% in the general community to 70% among household contacts.

The findings revealed a pattern of immune suppression persisting up to 37 months after infection.

The key markers, interferon gamma, interleukin-6, and tumor necrosis factor alpha, were all reduced in the COVID-recovered group. These aren’t obscure molecules. They’re the signaling chemicals that keep granulomas stable. Interferon gamma, in particular, is critical for activating the macrophages that form the granuloma’s inner wall. Without adequate signaling, those walls begin to crumble.

The study is small (40 participants split between two groups) and remains in preprint, awaiting peer review. But it offers a mechanistic explanation for patterns emerging in epidemiological data elsewhere. The researchers themselves note that “further studies are required to assess whether latent TB and COVID increase the long-term risk of progression to active tuberculosis.” The question is no longer theoretical. It’s now a matter of scale and timeline.

This scenario was predicted years earlier: regulatory cells becoming dysfunctional, macrophages growing “hyperactive” but ultimately exhausted, the entire granuloma structure degrading. Once bacteria escape containment, they can spread to new sites in the body and, critically, into droplets that reach other people.

The Korean Anomaly

If Pakistan provides the mechanism, South Korea provides the macro-level confirmation.

Korean health authorities recently published data tracking respiratory infections across the entire population from 2023 to 2024. The pertussis numbers alone should raise alarms. After hovering near zero throughout the pandemic, whooping cough cases exploded to 60,000 per month in 2024, mostly among younger people. Vaccination reduced symptomatic cases by 94% in older cohorts, which sounds reassuring until you consider what it implies: a massive population of asymptomatic carriers, circulating bacteria they cannot effectively fight.

The TB data tells a similar story. From 2016 onward, Korea’s tuberculosis incidence had been declining along a predictable trajectory. Then, around January 2021, the trend line broke: cases stopped falling and began to plateau. By 2024, the country was recording 47% more TB cases than anticipated based on pre-pandemic projections.

Korea is not a high-endemic region. It has strong public health infrastructure and high vaccination coverage for BCG, the tuberculosis vaccine that helps the immune system contain (though not eliminate) the bacteria. The fact that TB is resurging there, against the historical trend, suggests something has changed in the population’s baseline immunity.

Connect the micro-evidence from Pakistan with the macro-evidence from Korea, and a coherent picture emerges: population-level immune fatigue manifesting as resurgent ancient infections.

The Flip

The emerging situation demands uncomfortable directness: “This is one of those flip situations where now it may be that the unvaccinated have to protect themselves against everyone else.” Dr. McMillan observed.

The irony is bitter. For years, the public health message emphasized protecting the vulnerable through collective vaccination. Now, the data suggests a subset of that vaccinated population may be carrying and transmitting pathogens their compromised immune systems can no longer contain. The unvaccinated, whose immune responses may remain more robust against bacterial threats, find themselves in an unfamiliar position, potentially exposed by the very cohort that was meant to provide herd protection.

There are no pharmaceutical quick fixes here. The focus shifts instead to physiological defenses, particularly the role of nasal nitric oxide, a natural antimicrobial agent that can be boosted through simple practices like humming. It sounds almost quaint against the scale of the problem. But when immune systems are failing at the population level, individual protective measures become essential.

The Road Ahead

Degraded immune terrain, not the pathogen, is the real threat. A population with compromised immune function becomes fertile ground for diseases humanity thought it had contained. TB is patient. It has waited inside granulomas for years – even decades. It can wait a little longer, until the walls finally fall.

The timeline stretches out to five or ten years. But waiting for certainty is its own form of negligence. Public health authorities can begin identifying vulnerable cohorts and strengthening surveillance now, or continue playing catch-up with pathogens that have been planning their escape for decades.

The granulomas are holding. For now.