Yusra’s tiny body was hooked up to machines twice her size as her mother clutched the side of her cot, watching her baby fight for her life. Yusra had developed severe sepsis, which meant her body had turned on itself. As her immune system attacked her vital organs, doctors tried to treat her with various antibiotics. But there was a problem: the drugs weren’t working.
Yusra and her twin sister had been born two months early by C-section in Woldia, a hilly town in a region of northern Ethiopia blighted by violence between rebel and government forces. The hospital where they were delivered was still recovering from a rebel raid two years earlier that had stripped it of vital supplies. At six days old, Yusra’s sister died because she needed blood the hospital did not have.
Fearing she would lose this daughter too, her mother had taken her on a five-hour journey, past numerous military checkpoints, to a specialist hospital in Dessie.
Sepsis, which accounts for one in three newborn deaths in Ethiopia, is a condition whereby the body overreacts to an infection. It can be stopped by tackling infections early and treating them with antibiotics. But in Yusra’s case, it wasn’t that simple.
Doctors had treated her with so-called “first-line” antibiotics – drugs that are used on infections in the first instance – but they hadn’t worked. As they cycled through other types of antibiotics, her condition continued to deteriorate. And the drugs were expensive. Even if the doctors did find one that could save Yusra’s life, her mother might not be able to afford it.
Yusra’s story is part of a growing global emergency. Increasingly, infections that would once have been straightforward to manage with a course of antibiotics are no longer responding to drugs.
In 2019, drug-resistant infections were linked to nearly 5 million deaths around the world – more than HIV and malaria combined. Over 20 per cent occurred in sub-Saharan Africa, where the life-saving drugs that do exist can be in short supply, incorrectly prescribed and prohibitively priced.
“It’s happening on the scale of a pandemic,” says Nicholas Feasey, a professor at Liverpool School of Tropical Medicine. “African babies are dying in huge numbers because of this very widespread and severe illness.”
The problem is not confined to Africa. Around the world, the rate of resistance is growing and doctors on every continent are having to contend with infections that are nearly impossible to treat. But it’s patients like Yusra who are hit hardest.
A century of antibiotics
Antibiotics are the cornerstone of modern medicine. Without them, the risk of a deadly infection would be present every time anyone underwent routine surgery, gave birth or even scraped their knee falling over.
When Alexander Fleming discovered penicillin, the first ever antibiotic, in 1928, it ushered in a new age of medicine. Since then, it has been estimated that almost 500 million lives have been saved by penicillin alone. Illnesses like meningitis and rheumatic fever went from being commonly fatal to easily treatable.
But antibiotics are fighting a moving target. The bacteria that cause infections react to their surroundings and, if given enough chances, can “learn” ways of fending off the drugs designed to kill them.
When Fleming accepted the Nobel prize for his discovery, he issued a warning: these drugs had to be used sensibly because the bacteria they treat can become resistant.
Almost a century later, we now have more than 100 types of antibiotics. Some only kill specific bacteria while others work against a wider range. All have saved countless lives across the world. But Fleming’s warning has not been heeded.
In the last quarter-century alone, there has been an almost 50 per cent increase in the amount of antibiotics used on people around the world. Antibiotics are increasingly used by doctors as a first recourse for conditions that might not require them. Where resources are scarce, lack of access to diagnostic testing and vaccines can leave doctors with little choice. In many countries, too, certain antibiotics are available over the counter without a prescription.
This overuse of these drugs – combined with a lack of clean water, sanitation and hygiene – has driven an alarming increase in antibiotic resistance.
The result is that medical progress is effectively being reversed: infections from typhoid to pneumonia are becoming less easily treated with a simple round of drugs. Increasingly, they are becoming fatal.
Fighting for survival
With only around 50 beds in total and referrals coming from across the region, the babies’ intensive care unit in Dessie was constantly at capacity. The beeping of machines across the ward merged into a single, constant drone. In a separate room to Yusra, a mother was breastfeeding her newborn son, Adonias, who was also battling an infection.
Signs of neonatal sepsis include trouble breathing, fever, poor feeding and tiredness.
Following complications during his birth, Adonias was showing nearly all of them. But his local hospital didn’t have the testing facilities that would show which bacteria could be causing the infection – and therefore which antibiotics would have the best chance of treating it.
With no information to go on, they took a shot in the dark and prescribed Adonias the antibiotics most commonly used for sepsis. When days passed without them taking effect, Adonias was rushed eight hours to Dessie, his mother by his side.
But again, the hospital did not have the right testing equipment. And so again, the doctors had to gamble.
“We usually have to treat them blindly,” said Tarekegn Bitew, a neonatal doctor in Dessie’s intensive care unit. “If they don’t improve with the first-line antibiotics, we suspect clinical drug resistance and blindly prescribe second-line antibiotics.”
Prescribing blind is a regular part of the job for doctors like Terekegn, not least because hospitals can be a hotbed for infections. The high concentration of sick people and presence of antibiotics can lead to bacteria surviving, getting stronger and spreading between patients.
And if the wrong antibiotics are prescribed by doctors going on guesswork, the bacteria will continue to multiply, and the patient’s condition worsens.
In Adonias’s case, the second-line antibiotics seemed to be working. He was feeding more regularly and required less oxygen. But without testing there was no way to be certain.
Testing times
On the other side of the continent, in a neonatal ward in Lagos, lay Eniyoha, a week-old baby who had been abandoned by her parents at a hospital.
The hospital was in the midst of one of the power blackouts that plague the Nigerian city. And with the ward quickly losing daylight, the nurses prepared to do what they could to keep the babies warm.
The erratic power supply meant also that the patients’ medical records had to be kept on paper. Eniyoha’s file was already thick with notes detailing her condition, complications and treatments. She had been born eight weeks early with birth defects that meant lifelong physical impairments. Her parents had left her without an explanation, but hospital staff said it was likely to have been because they couldn’t afford the hospital bill.
Eniyoha also had drug-resistant neonatal sepsis. Almost all of the babies admitted at the hospital in Lagos are septic before they arrive.
With resources limited, the staff were doing what they could. For more than a year, they had swabbed the ward every day for bacteria and sent the samples for testing in government labs. The results were compiled and used to try and decide which drugs to use to treat the sick babies.
While the hospital didn’t have the means to test every baby for infection, it now had a cheat sheet: a list of antibiotics with a higher chance of success in treating these infections. This removed some of the guesswork, saving valuable time in the race to save lives.
This has never been more urgent. In Nigeria, one in every 29 babies die within four weeks of being born. Sepsis is one of the main causes. For premature babies like Yusra and Eniyoha, the odds of surviving a drug-resistant infection are even lower.
Counting costs
Eniyoha’s infection had not responded to either first or second-line antibiotics, so doctors were trying a third type. But many Nigerian hospitals do not cover the costs of any drugs, so for now, money from hospital donors was being used to foot the bill.
“It’s out of pocket,” said Folakemi Irewole-Ojo, medical director of the hospital, referring to the costs faced by patients needing antibiotics. “We come across parents that can’t afford treatment every day.
“It’s the long duration of treatment – by the time the preterm babies have spent two weeks here, [the parent’s] pocket is dry.”
For premature babies, hospital stays can last for weeks. And the bills rack up.
The concern was echoed by doctors in Ethiopia, where hospitals cover the costs of some drugs but not others. “The cost is also high, we don’t know which patient will be sensitive to which antibiotics,” Tarekegn said.
The standard approach, then, is to try the cheaper ones first. But if these fail, and a baby needs to be put onto so-called “last-resort” antibiotics such as meropenem, then the costs fall outside of the hospital’s budget. And a full course of treatment – around 20 vials – can cost five times as much as an average person earns in an entire month.
“If we had testing in this hospital, we would be able to improve patient management,” said Tarekegn. “It would also decrease the costs for the families.”
At times, in hopes of spreading costs and saving money, vials of medicine and other hospital equipment are shared among patients. This is especially common among babies as they require smaller doses of medication than adults.
High ceilings and concrete walls failed to keep the humidity low in the hospital ward in Dessie. Cots were spaced as far apart as possible to prevent the spread of infection, but a single vial of meropenem might sometimes be shared between three babies. Though it makes the most of scant resources, it can mean infections spread more easily across wards.
“Having to share hospital equipment is a major source of drug-resistant infections among neonates,” says Jonathan Strysko, a paediatrician and infectious disease epidemiologist based in Botswana. “It’s the fact hospitals have major reservoirs [of bacteria], like equipment that can never be fully cleaned.”
If not properly sanitised, the equipment is at risk of contamination by the bacteria that cause these fatal infections. “We need different ways of looking at infection prevention and controls in the hospital setting,” Strysko said. There is an added difficulty if hospitals do not have access to clean water.
In the neonatal ward in Lagos, the doctors’ cheat sheet had done its job: Eniyoha’s infection cleared. Social services are now trying to trace her parents. Back in Dessie, Adonias also continued to improve and was soon discharged from hospital.
Yusra, though, had not responded to second-line antibiotics. As her daughter’s health deteriorated, Yusra’s mother tried to get hold of meropenem before it was too late. It was on sale at pharmacies just outside of the hospital gates, but she didn’t have the money to pay for it. Her daughter died five days later.
Lives on the line
Half the babies introduced to TBIJ during a short visit to Dessie did not survive more than the first few weeks of their lives. It’s something these doctors and nurses witness time and time again.
“Most of the patients die,” said Tarekegn, the neonatal doctor. “Some of them do improve.”
And while the babies in his ward are among those worst affected by drug-resistant infections, they are far from the only ones put at risk by an increasingly global problem.
As more and more bacteria learn how to fend off human medicine, we are all at risk of dying from infections that are becoming untreatable. But for now, it’s the most helpless patients who find themselves on the frontlines.
Their access to testing equipment, vaccinations, clean water, sanitation and hygiene must all be addressed. As Feasey, the tropical medicine professor, said: “A holistic approach needs to be taken to prevent neonatal sepsis and to get those extremely vulnerable babies through the first 30 days of their life.”
Without it, he says, “the frailest members of African society will continue to die”.
