This is the first in a series of blog posts exploring the threat that drug resistance poses in fighting the epidemics of AIDS, tuberculosis (TB) and malaria. The full series is available here.

There are an estimated 37 million people living with HIV worldwide today. Tuberculosis causes 10.4 million people to become ill annually. And in 2015 alone, 212 million people were infected with malaria. The human suffering caused by these three diseases is incalculable.

Fortunately, many of those infected with these diseases are now able to receive lifesaving treatment and live long, healthy lives. Global efforts to eradicate HIV/AIDS, malaria and tuberculosis (TB) hinges on the successful treatment of these diseases, but drug resistance is jeopardizing that effort.

Drug resistance occurs when the germs that cause disease are no longer susceptible to the drugs designed to destroy them. Random mutations in disease-causing bacteria, viruses or parasites provide a defense against the drug, allowing the germ to live in the human body. The newly resistant “superbug” can then be passed to other individuals, causing drug resistance to spread across populations. Drug resistance has emerged in HIV, TB and malaria in recent years, challenging treatment efforts.

Even steadily maintaining the status quo in massive U.S. and global efforts against epidemics will risk resurgence; more strategy and resources are needed. Here, we examine the state of drug resistance, as well as the Global Fund’s efforts against it, for the leading cause of death from infectious diseases: TB.

Every three seconds, someone falls ill with tuberculosis. TB is caused by Mycbacterium tuberculosis, a bacteria that typically attacks the lungs, causing a chronic cough, fever, night sweats and weight loss. TB is an airborne disease, easily transmitted to others when an actively infected person coughs or sneezes. Someone with active TB can infect between 10 and 15 people over the course of one year. When untreated, TB is lethal. Nearly half of those infected die without proper treatment. In 2015, TB killed 1.8 million people, more than any other infectious disease.

However, TB is treatable. Drug-susceptible TB can be treated with a six-month course of four antibiotics. The regimen is difficult and complex; patients must take several pills daily, which can cause nausea. Consequently, sometimes patients do not take all of their pills, or they stop treatment early when symptoms begin to subside. This can foster drug resistance, as the incomplete dosage is insufficient to kill all of the bacteria, allowing resistant strains to reproduce. Moreover, incorrect prescriptions and poor drug quality can also contribute to drug resistance.

This has led to the emergence of multi-drug resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). MDR-TB is resistant to two of the four first-line antibiotics, and therefore requires a more complex, lengthy and expensive treatment regimen. Patients with MDR-TB must take second-line medication, which are more toxic and cause harsher side effects, for up to two years.

XDR-TB is resistant to both first- and second-line drugs, and in many developing countries, individuals diagnosed with XDR-TB are left without any treatment options at all. In more developed countries, treatment is possible but is extremely difficult and can cost up to $494,000 per patient. In 2015 there were approximately 580,000 cases of drug-resistant TB worldwide, about half of which were fatal.

To counter drug resistance, the World Health Organization treatment guidelines recommend directly observed therapy, short course (DOTS). DOTS involves health workers meeting TB patients daily to watch them take their medication and inquire about complications. While it ensures follow-through to skirt resistance, this places an enormous burden on both patients and health systems.

In Jakarta, 15 year-old Ambiya and her mother must take an hour-long bus ride to the hospital, where health care workers help her to swallow 11 nauseating pills. She and her mother make this trek daily to treat her MDR-TB. Before Global Fund investments enabled access to MDR-TB treatment, the hospital where Ambiya receives care would have had no drugs to offer her. While it is resource-intensive, DOTS is the best way to ensure that people like Ambiya adhere to their treatment and to prevent drug resistance from developing.

The Global Fund is the largest international donor for global TB programs, supporting treatment for 17.4 million people since 2002. Recognizing the critical threat of drug-resistant TB, the Global Fund has tripled the funding available to address MDR-TB over the past six years.

In particular, the Global Fund has created a catalytic investment to further enable innovative TB programming. Through this, the Global Fund has invested an additional $115 million in the 12 countries where 55 percent of all missed cases of TB, including MDR-TB, occur worldwide (Bangladesh, Democratic Republic of Congo, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, South Africa, Tanzania, Ukraine, Kenya and Mozambique).

In these countries and others, the Global Fund is helping to support the diagnosis and treatment of drug-resistant TB. The Global Fund invests in the distribution of GeneXpert technology to dramatically streamline the TB screening process. The Global Fund is also helping to expand access to two new drug-resistant TB treatments, bedaquiline and delamanid. These drugs have fewer side effects, ensuring greater adherence to treatment and stemming drug resistance. Finally, the Global Fund is investing in community programs and health care systems to help patients get through treatment and further prevent drug resistance.

Tuberculosis has overtaken HIV as the biggest infectious killer, but it is curable – and with high success rates for patients who stick to treatment. Epidemiological control of a disease that is millennia older than HIV is a goal worthy of U.S. leadership. It is achievable with strategic efforts to counter drug-resistance. International summits on TB are set for Russia in November 2017, and for the UN General Assembly next year. As an innovative public-private leader in the TB fight, the Global Fund should feature centrally in the strategy to neutralize drug resistance.

Click here to learn more about how the Global Fund is fighting drug-resistant TB.