After the discovery of Streptomycin in the 1940s, followed by isoniazid in the 1950s and later rifampin in the 1970s, the incidence of TB in the developed world dropped dramatically. Sanatoria closed and research into new antibiotics and vaccines likewise diminished. TB was no longer considered a significant threat in the US and much of Europe. So when multiple drug-resistant strains of TB (MDR-TB) appeared in the 1980s, the concern within the infectious disease community was perhaps understated. Besides, all but a small number of cases were in underdeveloped countries where the very high cost and difficulty of treating MDR-TB was considered beyond reach.
The 600-year tuberculosis epidemic continued to grow in regions of the world through the 1900's. If the organism was to be halted, a truly global public health strategy would be needed.
The seeds of change were planted when a graduate student named Paul Farmer visited Haiti in the 1980s. An admirer of the German Physician Rudolf Virchow (1821-1902), who we discussed in Part 1 of this blog, Farmer recruited fellow student Jim Yong Kim and others to come to rural Haiti to work as well. Both Farmer and Kim earned dual doctorates in Medicine and Anthropology at Harvard, and with their team they formed Partners in Health (PIH) to build a public health system in an area called Cange, 79 kilometers from Port au Prince, where TB was only one of several devastating health problems.
Turnaround in Treatment
To halt the spread of TB, the public health approach is identical to the medical approach – treating those who are sick, since patients receiving antibiotics quickly become non-infectious. PIH implemented the World Health Organization (WHO) system for treating TB, known as Directly Observed Therapy, Short-course, or DOTS for short. Directly observed therapy means that staff members ensure that patients receive all the different meds in the regimen, every day. The “Short course” part of DOTS was the first-line treatment, which lasted for four to six months. DOTS is more than 90 percent successful in treating TB and preventing the development of resistant strains.
To implement DOTS, Farmer and his team had to create a public health platform – they hired and trained members of the community as health workers, who visited patients and administered the TB meds, provided other care, and followed up if any missed a doctor’s appointment.
By the early 1990s, PIH was serving more than 100,000 people and was particularly successful in treating infectious diseases at low cost. The group was spending $150 to $200 in Haiti to cure TB, compared to about $15,000 to $20,000 in a US hospital at the time. However, treating TB typically requires not only medicine, but nutrition, clean water, and decent shelter. True to Virchow’s philosophy, the building of a public health platform (which, as in Berlin, included a new supply of clean water), and delivering care through community health workers, supported by a hospital, dramatically reduced overall mortality and morbidity from TB, as well as every other illness.
However, fate did not allow PIH to stay limited to Haiti. Farmer had friendships around the globe, and based on appeals from a friend, Jim Kim took the PIH platform to Peru. It was 1994 and Peru had a model DOTS program, but patients weren’t getting better. It was suspected that the program was failing in the face of MDR-TB, but the tools needed to diagnose drug-resistance were not available in the area where PIH was working – an area already struggling with poor nutrition, contaminated water, and insufficient housing. Given the lack of diagnosis, many insisted there was no MDR-TB and if there was, MDR-TB was considered untreatable in low-resource settings.
The problem was that the drugs used to treat MDR were both expensive and laden with unpleasant side effects, and the second-line regimen had to be followed for up to two years. Treating one patient for MDR-TB cost as much as $100,000 in the US at the time. Assisted by an angel in the form of a millionaire named Tom White, Jim Kim and Farmer began treating patients anyway, and when they succeeded, they stirred up the international community of TB experts, including some from Russia who asked PIH to come to Siberia.
In their path from Boston to Haiti to Peru and then to Russia, the PIH program had also reached Geneva. WHO had declared TB to be a global health emergency in 1993, and the DOTS platform was modified to include DOTS-plus for the treatment of MDR-TB. However, no one had the funds needed to even begin to implement treatment for MDR-TB; treating a few MDR-TB patients would cost many countries’ entire public health budget for all TB patients.
Turnaround in Affordability
To address the single biggest barrier to halting the epidemic (read – cost) Kim in 1996 spearheaded a complex campaign to make the drugs affordable, and succeeded on multiple critical fronts:
- Kim convinced the WHO to list the second-line drugs needed to treat MDR as “essential drugs,” which signaled the generic manufacturers that there was a substantial market for the medicines.
- Kim worked with the WHO to implement a Green Light Committee to control availability and (given their toxicity and the risk of creating resistance to these “last chance” drugs) make sure the meds were administered under a DOTS-plus program that included drug-resistance testing.
- Most of the medicines were under expired patents, and the International Dispensary Association (IDA) got involved, including recruiting manufacturers to produce generics.
- Eli Lilly, who manufactured two of the antibiotics, agreed to donate a large quantity of the agents as well as grant drastically reduced prices on purchases.
- Doctors Without Borders also helped in the campaign, including contributing funds for initial orders.
- Kim approached the Bill & Melinda Gates Foundation, who gave $45 million in 2000, and many millions more after that.
By 2000, the price of most of the drugs used to treat TB had dropped by 85 to 95 percent. For perhaps the first time in human history, global mortality from TB began to decline as well. The DOTS-plus program, combined with the reduction in the cost of many of the drugs and WHO’s Millennium Development Goals (MDGs) are showing results: Between 2000 and 2014, global incidence of TB fell by 18 percent and mortality dropped around 50 percent. Global funding for TB programs has increased, but TB continues to receive less attention than malaria, and only a small fraction of the funding for HIV/AIDS programs.
Both shortages in the drug supply as well as the cost of the agents continue to present a barrier to eliminating TB in the US and overseas. The general principles of supply and demand do not appear to apply to TB medications, and the economics of TB control is complicated. The factors at work are many: A number of medications in the regimen are used off-label; some are manufactured by a single supplier; manufacturers change and prices increase; quality issues often limit production; expiration dates are short, discouraging stocking up; new meds, though developed largely with public funds, usually enter the marketplace at very high cost; and administrative practices sometimes prevent programs from purchasing the drugs that are available at reasonable cost.
Light at the End of the Tunnel?
Nonetheless, a global public health strategy against TB is now underway and includes many international organizations, such as the TB Alliance and others. Regarding our story:
- Paul Farmer and PIH, although serving as a catalyst in addressing TB on a global scale, resisted “specializing” in TB; PIH has expanded to underserved regions in Malawi, Rwanda, Mexico, and many other countries, and is addressing HIV, Ebola, Zika, and other illnesses.
- Jim Kim is now President of the World Bank, and is the only person with a medical background to have held the office to date.
- WHO specifically has taken numerous critical steps: World TB Day is one of seven global public health days held annually by WHO to mobilize support (this year’s World TB Day was March 24); WHO has announced the End TB Strategy by the year 2030, summarized in the 2015 Global Report on TB; and ending TB is one of the targets of the WHO Millennium Development Goals (MDGs)
All in all, Virchow would be pleased.
Fisher BioServices UK is currently collaborating with partners on a global phase III clinical trial to create a biobank of blood, urine and sputum samples taken from TB-positive patients during treatment. To learn more about the objective, methods, and progress of the first tuberculosis biobank in the UK, download our scientific poster below!