An alternative to antibiotics could work wonders in Africa. It isn’t being used.

In January, a burn injury patient was admitted to a hospital in Kenya’s western Rift Valley. After three months, the patient developed an infection. Doctors quickly prescribed the standard slew of antibiotics, but the infection persisted. In March, doctors swabbed the infection and sent samples to a nearby laboratory. Scientists there isolated a bacteria called Pseudomonas aeruginosa and then tested the strain against 10 different antibiotics in a petri dish. None of the drugs could kill the bacteria, which had evolved to evade and survive such medicines, in a process called antibiotic resistance. Because bacteria will always be able to evolve much faster than humans can create new antibiotics, antibiotic resistance is not only deadly for individuals, but also a cause for worldwide public health concern. In 2019, researchers estimated that more than 1 million people died globally from antibiotic-resistant infections. The toll is disproportionate: It’s likely highest in sub-Saharan Africa, and based on some estimates, Kenya has one of the world’s highest rates of drug-resistant infections. Scientists believe we might actually be accelerating the development of drug resistance because modern medicine and modern farming rely so heavily on the mass use of antibiotics to treat and prevent infectious diseases in people and enhance growth in animals. Countries in the global south, then, often struggle to access the latest cutting-edge treatments for drug-resistant infections. And even as this crisis deepens, antibiotic research and development remains stalled. No major US or European pharmaceutical companies are currently working to develop new antibiotics. Even if they were, it takes decades and at least $1 billion to develop new drugs. With no traditional, effective options available, the patient’s doctors turned to a decades-old but long-overlooked treatment: viruses that can kill infection-causing bacteria. Bacteriophages, or phages for short, are viruses that infect and kill bacteria, and because they are living entities, phages evolve alongside the bacteria they feed on. Some experts believe phages now hold the promise to fix one of our most pressing global health crises. In the US, doctors can apply for emergency or compassionate use authorization from the Food and Drug Administration to employ phage therapy when other options have been exhausted. The US military, which has long been a leader in this field, maintains a biobank of phages and funds phage-related discovery and research around the world. While Big Pharma isn’t leading phage development — much of its focus is toward more profitable drug markets — some small, private biotech companies are slowly entering the field to develop new, genetically modified phages for treatment. There are more than 80 clinical trials for phage therapy in various stages taking place in the US. [Image: Martin Georges, a senior medical laboratory technologist in Lillian Musila’s laboratory at the Kenya Medical Research Institute, collects polluted water in Kibera, a large slum in Nairobi, in October 2023. Georges and his colleagues will try to isolate bacteriophages from the sample and test them to see if they can be used to treat drug-resistant infections. https://platform.vox.com/wp-content/uploads/sites/2/2024/09/Vox_JessicaCraig_Phages_inline.png?quality=90&strip=all] Lillian Musila, a principal research scientist at the Kenyan Medical Research Institute in Nairobi, has for years been rooting out phages in the local environment and studying their effectiveness against various drug-resistant bacteria. In the lab, Musila’s team tested the bacteria causing the patient’s infection against 72 different phages they had in their biobank and found 36 that effectively killed it. Unfortunately, the patient’s doctors couldn’t use this phage therapy to treat the patient. Kenya, like many other countries in the global south, does not have the regulatory, manufacturing, or clinical infrastructure to use phages to treat patients. While clinicians, researchers, and policymakers in North America and Europe are increasingly turning to phages for treatment and are working to implement health policy, regulation, manufacturing protocols, and clinical guidelines, Kenya and other countries in Africa are severely lacking in the ability to follow suit. To date, phage therapy has not been used anywhere in Africa, according to Musila and Tobi Nagel, a phage expert and Fulbright Scholar who founded the nonprofit Phages for Global Health. Unless these barriers are dismantled, hundreds of thousands of lives will remain at risk. A brief history of phage therapy Phages actually predate antibiotics. They were first discovered by Felix d’Hérell, a French-Canadian microbiologist around a decade before some time before Alexander Fleming famously stumbled upon penicillin in 1928. After their discovery, phages were used to treat numerous infectious diseases, including one of the era’s most pernicious killers: cholera. But the use of both phages and antibiotics really took off with World War II. As infectious diseases – from malaria and dengue fever to dysentery, STDs, and wound infections – proliferated in every major theater of the war, US pharmaceutical companies produced massive volumes of antibiotics for American and allied troops. And while the US and its Western allies were able to take advantage of the big increase in antibiotic production, globally, there was a huge shortage of the drugs. Militaries and governments in other parts of the world turned to phage therapy as their major line of defense against infectious diseases. The therapy took off in the Soviet Union, in part, because d’Hérell founded a research institute in Tbilisi shortly after he discovered phages. --- Antibiotic resistance, briefly explained As I explained earlier this year, antibiotic resistance is a natural process. Bacteria, like all living things, are just trying to survive, so they develop ways to avoid being killed by antibiotics. Antibiotics have brought tremendous health gains, but their waning effectiveness threatens all of that progress. Check out Vox’s coverage: * Drug-resistant bacteria are killing more and more humans. We need new weapons. * Antibiotics are failing. The US has a plan to launch a research renaissance. * Big Meat just can’t quit antibiotics --- For decades, phage therapy remained largely relegated to Eastern Europe. A few researchers in the US, including the military, continued researching phages in the lab, but it wasn’t being used in a clinical setting. That began to change in 2015. That year, Steffanie Strathdee, then the division chief of global public health at UC San Diego, and her husband Tom Patterson were vacationing in Egypt. There, Patterson picked up an infection caused by a bacteria that his doctors said was resistant to all known antibiotics. He was medically evacuated back to the US, where he fell into a coma. Strathdee, desperate to find a treatment for her husband and drawing from her background in microbiology, stumbled upon an online article about phages. She found military and academic scientists who were researching phages in relative obscurity and persuaded them to test the bacteria causing her husband’s infection against any phages they had stored in their labs. A few weeks later, they found one. Patterson’s doctors administered phage therapy through an IV line in his arm. Days later, Patterson awoke from his coma and ultimately survived his infection. It was the first documented IV phage therapy in the US. Since then, study after study has reported that phage therapy is not only largely effective against different types of infections, but it is also safe. A few scattered studies report that patients experience side effects such as fever and low blood pressure during phage treatment, but otherwise no published study has reported major life-threatening side effects from phage therapy. Despite the mounting evidence that phage therapy is safe and effective, uncertainties remain. For one, while we know that phages target and kill specific bacterial cells, Nagel explained that researchers aren’t entirely sure how phages interact with the human immune system. Phages are viruses, so does the immune system develop antibodies against phages in the same way it does against invading bacteria or viruses? “We don’t fully know, and the data that we do have so far seems to suggest that it will depend a lot on the specific phage,” said Nagel. Another concern is that because phages are living viruses that are also constantly evolving, they may adapt to target bacteria other than the one doctors are trying to treat, or could mutate in another unforeseen way that could be harmful to patients. It hasn’t been documented yet, at least among published studies, but it may be possible. This is, of course, not a concern with antibiotics, which are chemical compounds and not living, evolving organisms. At present, no one in the Western world can just walk into a pharmacy and order a vial of phages. The US, Canada, and countries in Europe are just now putting together clinical treatment protocols, regulations, and guidelines that spell out the exact steps to get a phage from a laboratory to a clinical setting. All the patients who have been treated with phage therapy in the US outside of clinical trials have been treated under an FDA emergency use authorization as Patterson was. This typically requires a doctor reaching out to various laboratories around the country trying to find an exact phage-bacteria match. When one is found, the laboratory grows some phage, purifies it, and then sends it off to the hospital where doctors prepare it, usually as an intravenous injection, for the patient. This can take anywhere from a few days to a few weeks. For larger-scale use and for late-stage clinical trials, which are needed to ensure that the therapy is safe and effective for the general population, phages will need to be manufactured according to a consistent protocol that adheres to good manufacturing practices. This would require sterile manufacturing sites and entire teams dedicated to producing the drug, testing its quality, and bottling it for distribution. Getting phages to Africa While there are barriers to the global use of phage therapy, in many countries in Africa where the need for such treatment options is greater, the hurdles are even higher. Many African governments lack the regulatory authorities and mechanisms to approve completely new therapies. Historically, medical regulators in Africa such as the Pharmacy and Poisons Board — Kenya’s equivalent to the FDA — only approve drugs or vaccines once they have already been approved in other countries that have rigorous vetting processes in place to ensure that drugs are acceptably safe and effective. Kenya’s Pharmacy and Poisons Board has never before approved a domestically manufactured drug. [Image: A scientist in Lillian Musila’s laboratory holds a petri dish where bacteriophages have killed bacteria leaving behind a tell-tale clear circle called a plaque. https://platform.vox.com/wp-content/uploads/sites/2/2024/09/Vox_JessicaCraig_Phages_lede.png?quality=90&strip=all] One way around this might be for physicians in Kenya or other African countries to import phages from abroad, at least initially. This would be expensive, come with significant delays, and may not be feasible in situations where patients are critically ill. In the long run, this approach is not very sustainable, but it may help kick-start phage therapy in Kenya and elsewhere in Africa. Another sticking point: Given that phages and bacteria evolve together, phages that originated in the local environment where they will be used may be more effective than those found abroad. Different countries have different types of drug-resistant bacteria, so what is a priority in Europe may not be a priority in Africa. Longstanding barriers to drug development in Africa, including a lack of manufacturing infrastructure, also remain an obstacle for phage therapy. But this may be a problem for the future. When patients are treated with phages in emergency use situations, phages are usually grown and purified in academic or university laboratories, not sterile drug manufacturing sites. Regulatory bodies in the US are just now grappling with the manufacturing challenge as clinical trials reached phase 3 stages. Musila and her team took a huge first step toward introducing phage therapy into Kenya and Africa more broadly. That they were able to quickly identify a slew of phages that were effective against the bacteria causing the patient’s drug-resistant infection demonstrated that researchers have the phages, the laboratory infrastructure, and the know-how in hand to make this lifesaving treatment, at least on a patient-by-patient basis. But the policy and regulation barriers around phage treatment in Kenya meant that the patient’s clinicians could not apply for emergency authorization and then receive it quickly enough to save the patient’s life, as is the case in the US and many European countries. Unfortunately, the burn patient died of his infection. A potentially lifesaving treatment was sitting in a nearby laboratory, unable to make it to the patient in time.

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An alternative to antibiotics could work wonders in Africa. It isn’t being used.