Tuberculosis (TB) is at once a textbook disease and a political reality: a bacterial process that is microbiologically well understood — and yet cannot simply be “treated away” globally. Derek Sloan, MD, infectious disease specialist and senior lecturer at the University of St Andrews, St Andrews, Scotland, sharpened this tension in a lecture to the Royal College of Physicians of Edinburgh, Edinburgh, Scotland. He argued that antibiotics are crucial, but without stable social structures and healthcare systems, they remain an inadequate solution.

Medicine Meets Society

Sloan has long worked in clinical infectious diseases and global TB care. He spent extended periods in east and southern Africa, including Kenya and KwaZulu-Natal (a province in South Africa). He later researched TB treatment in Blantyre, Malawi. A Wellcome Trust-funded PhD fellowship at the University of Liverpool in Liverpool, England, and a role as clinical lead in Sierra Leone during the Ebola outbreak shaped his view of TB as both a medical and a health system problem.

In his lecture, Sloan does not present the history of TB as a linear success story but as a sequence of breakthroughs and setbacks: Randomization arose from scarcity, resistance from monotherapy, and the officially described 6-month “short-course” standard treatment is a relative term. Epidemiologic trends reflect the success of individual drugs but are equally influenced by factors such as poverty, system collapse, and the dynamics of the HIV epidemic.

Although the decline in TB mortality in Western Europe began decades before the clinical introduction of streptomycin, Sloan’s central message is this: Biomedical innovation remains important, but at the population level, functioning public health systems, housing conditions, and poverty reduction determine long-term success. Medically, however, the introduction of streptomycin marked a historic breakthrough in TB treatment.

Breakthrough to Resistance

A key example for the start of antibiotic TB therapy is the London streptomycin trial of the late 1940s, considered one of the first randomized clinical trials for TB treatment. Randomization was driven not only by methodological interest but also by pragmatic reasons: The new drug was scarce, so random allocation seemed a fair solution. The clinical results were striking and marked the beginning of modern antibiotic TB therapy.

But disappointment followed quickly. Used as monotherapy, streptomycin selected for resistant mycobacteria; the bacterial load fell initially but then rose again after a short time. For Sloan, this was an early turning point in infectious disease medicine: Only a few years after introducing an effective antibiotic, it became clear that therapeutic success and resistance development are inseparable.

Combination Therapy Triumph

Streptomycin was followed by para-aminosalicylic acid and later isoniazid. The critical insight was less about any single new drug than the fact that combination therapies could cure and slow resistance. The price was early treatment regimens lasting up to 18 months, which were difficult to implement in routine care.

Sloan points to pragmatic progress in studies conducted in East Africa in the 1970s under the British Medical Research Council (often referred to as the Medical Research Council). With the introduction of rifampicin and pyrazinamide, treatment duration was shortened for the first time to 6 months. That model — a 6-month standard regimen — has remained remarkably stable: 2 months of four-drug therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampicin and isoniazid. Pharmacologically, the two key drugs have different roles — isoniazid rapidly reduces the bacterial load, whereas rifampicin eradicates more persistent bacterial populations.

The Limit to Shortening Therapy

In the East African Collaborative Trials of the 1970s, researchers tried to shorten treatment further to 4 months. At first, the results looked promising: The number of positive sputum tests dropped, and patients’ clinical condition improved quickly. But the real problem emerged after treatment ended. Depending on the combination used, 20%-40% of treated patients relapsed, especially when rifampicin played a lesser role.

That experience remains decisive: Reliably shortening the standard regimen below 6 months has not been achieved without accepting higher relapse rates. The consequences are not only scientific. A 6-month regimen demands a high degree of adherence — often in healthcare systems with scarce resources and under social conditions where transport costs, stigma, or economic pressures determine the course of treatment. Sloan describes this challenge from his own experience as a TB control clinician in KwaZulu-Natal, where he cared for thousands of patients annually.

Costly Diagnostic Shift

For Sloan, TB diagnostics are less a question of new technology than of practical feasibility in the day-to-day reality of many programs. For a long time, diagnosis relied mainly on the classic Ziehl-Neelsen stain: Sputum is smeared, fixed, stained, and examined microscopically for acid-fast bacilli. The method is inexpensive but requires experience and ties up personnel and, for decades, has remained the main diagnostic route in many high-incidence regions.

New technologies are gradually changing these workflows. Fluorescence microscopy speeds reading, liquid culture shortens the time to organism detection, and molecular tests such as GeneXpert provide much faster diagnosis. The problem does not disappear, however; it appears in another form: Whereas a microscope slide costs only a few cents, machines and cartridges are substantially more expensive. Thus, despite technical advances, diagnostics remain a matter not only of sensitivity but also of financing, infrastructure, and practical implementability in routine healthcare.

TB as a Persistent Challenge

Sloan explains why TB did not disappear globally after 1990 with three main drivers. First, TB remains a disease of poverty; high incidence correlates epidemiologically with low per-capita income. Second, the collapse of public health systems after the end of the Soviet Union favored program breakdowns and reservoir formation, for example, in prisons. Third, HIV has changed the risk profile: It accelerates progression from infection to disease and can complicate diagnosis because sputum bacterial loads may be lower.

Despite an effective and inexpensive standard therapy, case numbers rose for years before international programs produced measurable effects. For Sloan, this is a recurring motif: TB is not a newly emerging crisis but a disease that persists despite medical progress.

Interruptions Fuel Resistance

Where the 6-month standard regimen is not reliably completed, the risk for resistant strains rises. Sloan describes how treatment interruptions and irregular drug intake favor multidrug-resistant TB. Clinically, this breaks with first-line therapy: Instead of well-tolerated standard regimens, patients face longer, more toxic second-line treatments — often lasting many months and long lacking a strong evidence base. Only in the 2010s did the picture begin to change: New drugs such as bedaquiline and delamanid made shorter, fully oral regimens possible and improved cure chances, even for highly resistant TB.

At the same time, Sloan emphasizes that every therapeutic innovation also brings new risks: Soon after the introduction of new drugs, early reports of resistance appeared — echoing the early history of streptomycin. Even with new agents, TB therefore remains less a closed chapter than an ongoing process.

This story was translated from Univadis Germany, part of the Medscape Professional Network.