Not only does the current Russia-Ukraine pose unique risks of regional and global military escalation, it is also creating historic levels of population displacement and military mobilization of convicts, in one of the world's foremost multi-drug-resistant tuberculosis hotspots.
TB, or "consumption" is an ancient disease, closely associated with malnutrition and overcrowding. It is the disease that killed Chekhov, Chopin, Emily Bronte, Orwell, Kafka, Keats, Thoreau, and many others at the height of their creative years.
TB is caused by the bacteria 'Mycobacterium tuberculosis'. Mycobacteria have evolved a waxy coating which allows them to survive and reproduce inside macrophages, thus evading our immune system's first line of defense. Tuberculosis can remain latent within the body for many years, becoming active once the immune system is sufficiently weakened by factors such as malnutrition, diabetes, HIV, or smoking. A patient with latent TB has a 5-10% lifetime chance of developing active TB. Classic symptoms of active pulmonary TB include night sweats, weight loss, and a cough that produces blood-tinged sputum. Untreated, pulmonary TB eventually destroys the lungs in a "swiss cheese" pattern, and leads to patient death. TB bacteria may also disseminate throughout the body, creating a variety of symptoms, such as cutaneous nodules, engorged lymph nodes (scrofula), meningitis, and an array of internal organ problems.
TB is the world's top infectious disease killer, and fully 1/4 of the world population currently carries latent tuberculosis. Infection rates vary locally, ranging from as low as 3% in some developed countries, to 90%+ in parts of Africa. Only patients with active TB can pass the bacteria on to others, and may infect 15 other individuals per year. Conflict and other social disruption events can have a major impact on spread. Firstly, conflict subjects individuals to physical hardships, such as poor nutrition, inadequate housing, and exposure to other infectious diseases. Second, conflicts displace populations, and lead to overcrowding, poor sanitation, and breakdown of healthcare systems. Studies suggest that war increases annual TB incidence up by up to 20%. The 2022 Russian invasion of Ukraine has resulted in the fastest mass refugee migration since WWII. In 2022, the world-wide number of displaced persons hit a new record of over 100 million souls.
Social disruptions do not have to be conflict-based to facilitate the spread of TB. Russia and other former USSR members have the developed world's highest TB rates, due to social disruptions that occurred during the decade after the fall of the USSR. The 1990's reversed a huge amount of Soviet progress on TB control, which had been achieved via xray detection, isolation, and treatment in sanitariums. Infection rates in Russia fell from 1910 levels of 400/100,000, down to a rate of 17.3/100,000 (in men) and 1.9/100,000 (in women) in 1990. But post-Soviet poverty and healthcare system collapse caused Russian TB rates to double between 1991-1998. During the same time period, incarceration rates tripled in most post-Soviet states. By the late 1990's, TB had become a raging epidemic within the overcrowded Russian prison system, with prisoner infection rates averaging 4,000/100.0000, and in some regions reaching 7,000/100.000.
Mycobacterium tuberculosis's ability to hide from the immune system means that treatment regimes, even for cases that are susceptible to first-line antibiotics, are lengthy. If, due to treatment costs, disruptions in health services, or poor patient education, a patient stops treatment early, evolutionary forces favor the growth of antiobiotic-resistant bacteria within that patient's body. This resistant bacteria can then be passed on to others, garnering new opportunities, with each unsuccessful treatment course, to become resistant to additional medications. The result is multi-drug-resistant TB, or "MDR-TB"- one of today's major public health challenges. Treatment regimes for MDR-TB last up to two years, may cause uncomfortable side effects, and have a significant failure rate. To reduce risk of MDR-TB, DOTS, or Directly Observed Treatment, has become the gold standard for TB treatment worldwide.
However, in post-Soviet states, corruption and economic woes interfered with successful TB programs. Physicians opposed DOTs, feeling that it threatened their already precarious livelihoods. TB medications were re-purposed and sold in markets by crooked pharmacists, or traded for other items by prisoners in treatment programs. Until fairly recently, antibiotics were widely available without prescription at pharmacies in both Russia and Ukraine. It was quite common to self-prescribe an inappropriate course of antibiotics, for example, for a viral cold infection. By 1998 20% of Russian prison cases were MDR-TB. As prisoners were released mid-treatment, this trend spread into the general population. Eastern Europe now accounts for the largest MDR-TB burden in the world.
In recent years Russia, along with many former Soviet states, has resumed making progress on TB control. Between 2010-2020, Russian TB mortality halved, and general population infection rates fell to 45-50/100,000 (48% MDR-TB). WHO estimated 2021 TB incidence in Ukraine to be 71/100,000 (31% MDR-TB in new cases and 45% in relapse cases). In contrast, average 2021 TB incidence in the EU was 8.4/100,000 (33% MDR-TB). Thus, TB infection in refugee populations moving from Eastern to Western Europe is a major public health concern.
Despite progress within prisons, as well as amongst the general population, TB remains a major problem in Russian prisons. Russia has one the world's highest incarceration rates, with overcrowding and poor living conditions extremely common. A 2017 study estimated that 1 in 10 Russian prisoners have active TB, and that the majority of remaining prisoners have latent infections. A 2019 study found that Russia had the world's second-highest number of new active TB cases amongst prisoners (~13,000 cases, second only to 15,000 cases in Brazil). A 2-3 yr prison sentence leads almost inevitably to TB infection. 48% of Russian prison cases are multi-drug-resistant. Russia also has one of the highest rates in the world of "extensively drug-resistant TB", which is even more difficult to treat than MDR-TB. Russia's heavy reliance on convicts as soldiers, low health standards for enlistment, difficult frontline living conditions, unreliability of medication supplies, potential for injury or capture, and inter-mixing with and displacement of civilian populations all create a major risk for wartime transmission of TB, MDR-TB, and XDR-TB.
In the Ukraine war, post-Soviet health challenges are potentiated by the melange of convict soldiers, frontline conditions, and mass displacement of civilians. The result is a myriad of spread opportunities for the world's new diseases of disruption: MDR-TB, MDR wound infections, and potentially also novel respiratory viruses (think a new wartime COVID variant or a 1918-style influenza).
Spread of MDR-TB is not the only concern. TB comes in a variety of strains. Interestingly, the prevalent strain in Russia is the "Beijing" type. The Beijing TB strain, first described in 1995, has unique proteins. These potentially make it more infectious and more resistant to treatments. A 2020 literature review of studies involving 7,000 patients found strong support for correlation between the Beijing strain and more unfavorable treatment outcomes. Despite global implementation of DOTS, TB incidence seems to be declining at only 1-2%/yr- far slower than math models predict. The reasons for this include prevalence of HIV coinfection, diabetes, malnutrition, drug resistance, crowding, and poor control infrastructure. Arguably, another reason is the spread of Bejing subtypes- which will also likely be further facilitated by the disruptions of the Ukraine war.
There is hope on the horizon for TB control. A currently approved vaccine, the BCG TB vaccine, does not prevent TB, but it does serve to lessen risk of some severe forms of disseminated disease in children. Several vaccines designed to prevent pulmonary TB in all ages are currently under development. The most promising is M72. M72 was dropped by its original creator due to low profit potentials, but has recently been picked up by the Gates Foundation and has entered Phase III trials. M72 may be able to prevent pulmonary disease in 54% of infected adults. And for a disease that can take years to treat, and becomes active in 5-10% of patients, who go on to infect 15 other people per year, 54% prevention be a game-changing statistic.
WHO TB page
WHO TB Surveillance and Monitoring in Europe, 2023
The 2020 clinical update by the Global Tuberculosis Network
2020 Stanford-China study: Mycobacterium tuberculosis Beijing genotype strains and unfavourable treatment outcomes: a systematic review and meta-analysis
2017 literature review: Multidrug resistant tuberculosis in prisons located in former Soviet countries: A systematic review
No comments:
Post a Comment