As African kids died, doctors fought for ban on toxic Indian syrup

A known toxin lurked in the syrup taken by children in Gambia and doctors face a fight to prove it

Last July, more than 20 children were admitted to the Paediatric Emergency Unit of the Edward Francis Small Teaching Hospital in Gambia with kidney failure. Many received dialysis, the usual treatment.

Nearly all died.

Doctors were mystified, four of them said: They usually see one or two such cases a year. Consultant paediatrician Vivian Muoneke, a 33-year veteran, was scared.

"I had never seen anything like this," she said. "It was like an epidemic."

It was the rainy season; Gambian health ministry officials thought the problem was contaminated water. But Muoneke and her colleagues suspected the children had been poisoned.

Three months later, the deaths of more than 70 Gambian children from Acute Kidney Injury were linked by global health officials to cough syrups made in India and contaminated with ethylene glycol (EG) and diethylene glycol (DEG). The patients were the first of about 300 children killed worldwide last year by contaminated cough syrups, not all of them made in India. It was the deadliest total poisoning on record from toxins that have been known to scientists for decades.

As authorities search for a culprit in this case, the story of how the Gambian doctors raised the alarm, then pushed for weeks for health officials to test for chemical poisoning and ban cough syrup sales, has not been previously reported.

Delays in testing the medicines cost weeks. When completed with help from the World Health Organization (WHO), the tests showed the medicines contained extremely dangerous levels of the toxins and had been sold in bottles wrongly labelled as WHO-approved.

Pharmaceutical experts have warned for years about lax oversight of drugs made in India, whose industry supplies nearly half of the generic medicines used in Africa. India's health regulator says it found no fault with the medicines.

The Gambian case appears to be the first documented example of DEG poisoning from imported rather than domestically produced medicines, a group of experts from Gambia and the US Centers for Disease Control and Prevention said. The tragedy shows the difficulties faced by a poorly resourced country in identifying and removing harmful products, the experts said.

"There is not enough consequence when your drugs have been found to fail quality tests in a small African country," said Jude Nwokike, vice president of the Promoting the Quality of Medicines Program at US Pharmacopeia (USP), a non-profit partly funded by the United States that helps set drug-making standards globally. "That really needs to change."

Indian authorities closed the factory that made the drugs in October. Government inspectors found their manufacturer, Maiden Pharmaceuticals Ltd, had violated rules "across its manufacturing and testing activities." Maiden Managing Director Naresh Kumar Goyal said he had "not done anything wrong" and did not respond to further questions. He was keen to reopen his plant.

Goyal has since been convicted of manufacturing lapses that occurred a decade ago. Court documents did not note how he pleaded.

In December, India's health regulator said it did its own tests and found no toxins in the syrups. Government officials said the WHO had failed to prove a causal link to the Gambia deaths and accused the agency of denigrating its $41 billion pharmaceutical industry, according to a letter from the regulator to the health agency.

"It is absolutely clear that WHO has not established … a direct link between the consumption of the concerned cough syrups made in India and the deaths of children in Gambia," said India's health ministry in a statement.

The WHO says establishing that link is not the point.

"The issue is not about proof of causation," said WHO spokesperson Margaret Harris. The toxins found in the Maiden syrups "should never be ingested by human beings."

Similar poisonings – involving cough syrups made in Indonesia and by a different company in India – emerged later, in Indonesia and Uzbekistan. Police in those countries have arrested and charged chemicals traders, importers and regulators with improperly selling industrial-grade chemicals as suitable for pharmaceutical use, or failing to test the products.

In January the WHO sounded the alarm over the safety of cough syrups globally.

"CYANIDE IN A BOTTLE"

In 1937, DEG used in an antibiotic killed 107 people in the United States. Since then, the toxins have been found to cause at least 16 mass poisonings worldwide.

DEG is used in car brake fluid and radiators. Cats and dogs attracted by the sweetness often die after licking it off the ground, said Leo Schep, a toxicologist at New Zealand consultancy ToxInform who published a peer-reviewed paper on DEG poisoning.

"It is like putting cyanide in a bottle of paracetamol," Schep said.

After the US deaths, American lawmakers empowered the Food and Drug Administration to check drugs for safety before they go on sale. Other rich countries have similarly strong checks.

But Gambia is one of Africa's smallest and poorest countries. It has no pharma industry, no means of testing imported drugs, and just over two dozen pharmacists registered for 2.5 million people.

The first case at Muoneke's hospital was a two-year-old boy on July 7. Within a week, five more children were admitted.

The hospital had enough dialysis catheters for three patients, said deputy chief medical officer Abubacarr Jagne. He drove to neighbouring Senegal in search of more, eventually ordering nine from Nigeria.

The health ministry alerted the WHO to the children's cases, and the agency offered help. There was a chance E.coli bacteria in flood water was causing the deaths, the doctors said, but they had never seen E.coli infections as lethal.

The patients' histories showed the children had taken syrup for minor illnesses days before they were hospitalised. They soon began vomiting and had diarrhoea. Then they stopped urinating. Drowsiness set in, they lost consciousness. Their pupils became dilated and fixed. Blood tests showed poor kidney function.

Yet even as the doctors' evidence of toxins mounted, Gambian government officials said they wanted more proof. For two months, the government did not mention possibly risky syrups in public statements.

"For us it was psychological torture," said Muoneke. "We took their histories and asked them if they took the drugs, and we just knew" that the syrup was the culprit. If tests for toxins had been done in late July or early August, a sales ban could have saved dozens of children, she said.

Health Minister Ahmadou Lamin Samateh did not respond to that point but said in November he acted fast when he became aware that drugs were the most likely cause.

"We are no longer seeing cases, so did the government and the team do well? I think we did extremely well," he said. The ministry's director of health services, Mustapha Bittaye, said it would not comment further ahead of a government report on the matter.

FROZEN

Binta Ceesay keeps a picture on her phone of her triplets Ali, Moustapha and Mohamed, shortly after they were born.

Last July, her seven-month-old babies caught a cold. Ceesay said she bought them medicine. Three days later, they had diarrhoea and were vomiting. They stopped passing urine. On July 26, all three were admitted to a hospital south of Banjul.

Ali's mouth and nose began to bleed, she said. "He couldn't do anything. It was like his body was frozen."

Ali died on July 29. Two days later, Moustapha died.

Ceesay led a reporter to an overgrown cemetery where the two boys are buried a few yards apart in unmarked graves, according to a common tradition in conservative Muslim Gambia.

She took Mohamed to Muoneke's hospital. Doctors asked if he had taken any medicinal syrups: She showed them the medicines. They took photos and confiscated them, she said.

Doctors at the hospital said health ministry officials removed many case files for investigation. The ministry did not respond to a request for comment on Ceesay's account.

Over 10 days in Banjul, Mohamed recovered. But months on, he still cries when he urinates. His mother worries the episode has affected his development.

"WHO-CERTIFIED"

The drugs were in a batch of 50,000 imported bottles of four syrups containing active ingredients including paracetamol, which is known as acetaminophen in the United States. Made by Maiden, they were sold as Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup. Maiden is based in India's Haryana state and says it exports medicines to more than 40 countries.

Regulatory documents show its manufacturing practices had fallen short at least three times. In 2011, India's Bihar state blacklisted the company for five years for selling substandard and "spurious" (adulterated) medicine. In March 2022, two drugs manufactured by Maiden were found by Kerala state to miss quality standards. Last month, an Indian court sentenced Goyal and another executive to two-and-half years in jail for quality violations in drugs sold to Vietnam a decade ago. It gave them a month to appeal.

Despite this record, Haryana's Department of Food and Drug Administration (FDA) licensed Maiden to produce for export. Asked why, the Haryana FDA and India's health ministry did not respond.

The packaging on Gambia's Maiden cough syrups was marked with the WHO's logo and the wording "WHO-GMP certified," images issued by the agency show.

The WHO said Maiden had no right to use this wording or its logo, a message the agency's lawyers have sent to the company, according to emails. The agency does not provide certificates showing companies comply with Good Manufacturing Practices, Harris said.

AUTOPSIES

Acute Kidney Injury (AKI) can range from minor loss of function to complete kidney failure, which is what Muoneke and her colleagues were seeing in the children.

To prove medicines were the cause, they needed the drugs tested and patients autopsied. But post mortem examinations of bodies are rare in Gambia, based on the religious belief they desecrate the body before burial.

Muoneke met dozens of bereaved parents to try to persuade them. Two families agreed to 15-minute autopsies, but the results were not released by the hospital pathologist for a month.

On Aug. 6, the health ministry sent the first of 89 samples of stools and urine from children across Gambia to the National Public Health Laboratories in Banjul. That lab couldn't do the necessary tests, so some samples were sent to the Institut Pasteur in Senegal, 300 km (186 miles) away.

Ministry director Bittaye said that only five of these had harmful E.coli.

"If you are looking at it now, with all the data and all the patients, it more points away from E.coli," he said.

Then attention turned to testing the medicines. On Aug. 8 the ministry, with help from the WHO, sent medicine samples to the Centre Anti Poison du Senegal in Dakar. Worried a courier would take too long, officials drove them there themselves.

With cases arriving almost daily, the hospital on Aug. 9 issued a statement warning people not to use any drug purchased from a pharmacy without checking with a health facility first. But the health ministry was silent on the syrups.

MULTI-ORGAN FAILURE

By late August, Muoneke was seeing about nine cases a week, losing patients, but still waiting for results on the medicines.

The post mortem reports showed the children had suffered the destruction not just of the kidneys, but also of the spleen, liver, lungs and pancreas, Muoneke said. The extent of the damage was another indicator of chemical poisoning.

Because of the parents' concerns about post mortem exams, the autopsies were not as thorough as the doctors wanted, Muoneke said. A complete autopsy would take at least an hour, said Barbarajean Magnani, a professor of anatomic and clinical pathology emerita at the Tufts University School of Medicine in the US

Muoneke's then head of department, Professor Egbuna Olakunle Obidike, met Bittaye from the health ministry on Aug 31 to share the news about the organ failures.

"I presented it strongly to him that the facts at our disposal clearly pointed to medicines," he said.

But the Centre Anti Poison du Senegal, which was testing the medicines, told Gambian authorities it could not test for EG and DEG.

On Sept. 4, the health ministry released a statement about the AKI deaths. To the doctors' frustration, it did not mention the risks of paracetamol syrup but it did refer to unsanitary water, recommending people wash their hands and cook food well.

Muoneke said she met health minister Samateh at the hospital days later to "let him see why he should ban the drugs for a trial."

Finally, on Sept. 7, the health ministry told hospitals and regional health officials to ban every brand of paracetamol syrup from sale. Samateh did not say what triggered that or explain why the Sept. 4 statement had not mentioned the drug risk.

"IRREPARABLE DAMAGE"

The next day, the government and the WHO sent the medicine samples 2,000 km away to the US Pharmacopeia lab in Ghana, which could test for toxins. These found EG and DEG in some, but could not determine how much.

So the team sent medicine samples to another location: the WHO-approved Intertek Laboratory in Reinach, Switzerland.

The results, on Sept. 26, showed dangerous levels of DEG and EG in all four samples produced by Maiden, the WHO said. The lab also tested 19 samples made by other manufacturers that children in Gambia could have taken.

"All except the products from Maiden tested negative for the contaminants," spokesperson Harris said.

That fortnight, Gambia saw only two new AKI cases, which the minister later said was proof its ban had succeeded.

The WHO said it immediately shared the information with the authorities in India and Gambia, as well as Maiden, and published its findings on Oct. 5.

The next day, India's health ministry said it was the responsibility of the importing country to test medicines they buy from India.

In ensuing weeks Prime Minister Narendra Modi's government asked the WHO to prove the link between the drugs and the deaths – an assessment the U.N. health agency says is down to Gambia. Toxicology experts said establishing conclusive proof could be difficult even if the Gambian authorities were able to conduct the extensive autopsies that parents did not want.

The WHO in turn asked India for complete data on its tests of Maiden's drugs, but has not received this, according to emails and statements from the agency.

In December, India's then drugs controller general, VG Somani, told the WHO the global health agency's alert had been premature because the link to the deaths was not proven.

The warning, Somani protested, had "adversely impacted the image of India's pharmaceutical products across the globe, and caused irreparable damage to the supply chain of pharmaceutical products," according to an email.

Gambia's health ministry did not comment about Somani's complaint. The WHO did not respond directly when asked about Somani's email, but said it would continue working with governments to remove unsafe medicines from use.

"I WANT TO GO HOME"

For some children, word of Gambia's ban on cough syrups came too late.

Three-year-old Lamin Sagnia was usually full of energy, his father said, gesturing to the family couch that he said Lamin had torn by leaping about. The boy loved jokes, and would sit on his father's lap when he drove his old Mercedes around the neighbourhood.

On Sept. 7, Lamin developed a fever.

Fearing it was malaria, his father, Ebrima Sagnia, drove Lamin to the Precious Drug Store in Serekunda. A doctor, Comfort Smith, recommended a cough and paracetamol syrup. The manager did not tell her until the next afternoon they were banned, she said.

"If I had realised this sooner, I would not have sold him the drugs."

Lamin took the medicines that night. By the next day he was unable to urinate. Sagnia drove his son to the Banjul hospital.

Lamin was sleeping continuously. He did not respond to repeated rounds of dialysis.

Sagnia left his son's bedside briefly to buy bananas, milk and juice, but Lamin lay with his tongue out, unable to eat. "He was looking somewhere else different from this world," Sagnia said.

On Sept. 12, Lamin came round and spoke.

"Dad, I want to go home," he told his father.

"Very soon we will go home," Sagnia responded.

Lamin died the next day.

Sagnia is now a spokesman for a coalition of parents calling for systemic reforms. The government initially offered families 14,000 dalasis ($200) each, he and another parent said. The families rejected the sum.

Their main goal, he said: to ensure this never happens again.