From her base in Gallup, New Mexico, Melissa Wyaco supervises about two dozen public health nurses who crisscross the sprawling Navajo Nation searching for patients who have tested positive for or been exposed to a disease once nearly eradicated in the U.S.: syphilis.

Infection rates in this region of the Southwest — the 27,000-square-mile reservation encompasses parts of Arizona, New Mexico, and Utah — are among the nation’s highest. And they’re far worse than anything Wyaco, who is from Zuni Pueblo (about 40 miles south of Gallup) and is the nurse consultant for the Navajo Area Indian Health Service, has seen in her 30-year nursing career.

Syphilis infections nationwide have climbed rapidly in recent years, reaching a 70-year high in 2022, according to the most recent data from the Centers for Disease Control and Prevention. That rise comes amid a shortage of penicillin, the most effective treatment. Simultaneously, congenital syphilis — syphilis passed from a pregnant person to a baby — has similarly spun out of control. Untreated, congenital syphilis can cause bone deformities, severe anemia, jaundice, meningitis, and even death. In 2022, the CDC recorded 231 stillbirths and 51 infant deaths caused by syphilis, out of 3,761 congenital syphilis cases reported that year.

And while infections have risen across the U.S., no demographic has been hit harder than Native Americans. The CDC data released in January shows that the rate of congenital syphilis among American Indians and Alaska Natives was triple the rate for African Americans and nearly 12 times the rate for white babies in 2022.

“This is a disease we thought we were going to eradicate not that long ago, because we have a treatment that works really well,” said Meghan Curry O’Connell, a member of the Cherokee Nation and chief public health officer at the Great Plains Tribal Leaders’ Health Board, who is based in South Dakota.

Instead, the rate of congenital syphilis infections among Native Americans (644.7 cases per 100,000 people in 2022) is now comparable to the rate for the entire U.S. population in 1941 (651.1) — before doctors began using penicillin to cure syphilis. (The rate fell to 6.6 nationally in 1983.)

O’Connell said that’s why the Great Plains Tribal Leaders’ Health Board and tribal leaders from North Dakota, South Dakota, Nebraska, and Iowa have asked federal Health and Human Services Secretary Xavier Becerra to declare a public health emergency in their states. A declaration would expand staffing, funding, and access to contact tracing data across their region.

“Syphilis is deadly to babies. It’s highly infectious, and it causes very severe outcomes,” O’Connell said. “We need to have people doing boots-on-the-ground work” right now.

In 2022, New Mexico reported the highest rate of congenital syphilis among states. Primary and secondary syphilis infections, which are not passed to infants, were highest in South Dakota, which had the second-highest rate of congenital syphilis in 2022. In 2021, the most recent year for which demographic data is available, South Dakota had the second-worst rate nationwide (after the District of Columbia) — and numbers were highest among the state’s large Native population.

In an October news release, the New Mexico Department of Health noted that the state had “reported a 660% increase in cases of congenital syphilis over the past five years.” A year earlier, in 2017, New Mexico reported only one case — but by 2020, that number had risen to 43, then to 76 in 2022.

Starting in 2020, the covid-19 pandemic made things worse. “Public health across the country got almost 95% diverted to doing covid care,” said Jonathan Iralu, the Indian Health Service chief clinical consultant for infectious diseases, who is based at the Gallup Indian Medical Center. “This was a really hard-hit area.”

At one point early in the pandemic, the Navajo Nation reported the highest covid rate in the U.S. Iralu suspects patients with syphilis symptoms may have avoided seeing a doctor for fear of catching covid. That said, he doesn’t think it’s fair to blame the pandemic for the high rates of syphilis, or the high rates of women passing infections to their babies during pregnancy, that continue four years later.

Native Americans are more likely to live in rural areas, far from hospital obstetric units, than any other racial or ethnic group. As a result, many do not receive prenatal care until later in pregnancy, if at all. That often means providers cannot test and treat patients for syphilis before delivery.

In New Mexico, 23% of patients did not receive prenatal care until the fifth month of pregnancy or later, or received fewer than half the appropriate number of visits for the infant’s gestational age in 2023 (the national average is less than 16%).

Inadequate prenatal care is especially risky for Native Americans, who have a greater chance than other ethnic groups of passing on a syphilis infection if they become pregnant. That’s because, among Native communities, syphilis infections are just as common in women as in men. In every other ethnic group, men are at least twice as likely to contract syphilis, largely because men who have sex with men are more susceptible to infection. O’Connell said it’s not clear why women in Native communities are disproportionately affected by syphilis.

“The Navajo Nation is a maternal health desert,” said Amanda Singer, a Diné (Navajo) doula and lactation counselor in Arizona who is also executive director of the Navajo Breastfeeding Coalition/Diné Doula Collective. On some parts of the reservation, patients have to drive more than 100 miles to reach obstetric services. “There’s a really high number of pregnant women who don’t get prenatal care throughout the whole pregnancy.”

She said that’s due not only to a lack of services but also to a mistrust of health care providers who don’t understand Native culture. Some also worry that providers might report patients who use illicit substances during their pregnancies to the police or child welfare. But it’s also because of a shrinking network of facilities: Two of the Navajo area’s labor and delivery wards have closed in the past decade. According to a recent report, more than half of U.S. rural hospitals no longer offer labor and delivery services.

Singer and the other doulas in her network believe New Mexico and Arizona could combat the syphilis epidemic by expanding access to prenatal care in rural Indigenous communities. Singer imagines a system in which midwives, doulas, and lactation counselors are able to travel to families and offer prenatal care “in their own home.”

O’Connell added that data-sharing arrangements between tribes and state, federal, and IHS offices vary widely across the country, but have posed an additional challenge to tackling the epidemic in some Native communities, including her own. Her Tribal Epidemiology Center is fighting to access South Dakota’s state data.

In the Navajo Nation and surrounding area, Iralu said, IHS infectious disease doctors meet with tribal officials every month, and he recommends that all IHS service areas have regular meetings of state, tribal, and IHS providers and public health nurses to ensure every pregnant person in those areas has been tested and treated.

IHS now recommends all patients be tested for syphilis yearly, and tests pregnant patients three times. It also expanded rapid and express testing and started offering DoxyPEP, an antibiotic that transgender women and men who have sex with men can take up to 72 hours after sex and that has been shown to reduce syphilis transmission by 87%. But perhaps the most significant change IHS has made is offering testing and treatment in the field.

Today, the public health nurses Wyaco supervises can test and treat patients for syphilis at home — something she couldn’t do when she was one of them just three years ago.

“Why not bring the penicillin to the patient instead of trying to drag the patient in to the penicillin?” said Iralu.

It’s not a tactic IHS uses for every patient, but it’s been effective in treating those who might pass an infection on to a partner or baby.

Iralu expects to see an expansion in street medicine in urban areas and van outreach in rural areas, in coming years, bringing more testing to communities — as well as an effort to put tests in patients’ hands through vending machines and the mail.

“This is a radical departure from our past,” he said. “But I think that’s the wave of the future.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

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JoEllen Zembruski-Ruple, while in the care of New York City’s renowned Memorial Sloan Kettering Cancer Center, swallowed the first three chemotherapy pills to treat her squamous cell carcinoma on Jan. 29, her family members said. They didn’t realize the drug could kill her.

Six days later, Zembruski-Ruple went to Sloan Kettering’s urgent care department to treat sores in her mouth and swelling around her eyes. The hospital diagnosed oral yeast infection and sent her home, her sister and partner said. Two days later, they said, she returned in agony — with severe diarrhea and vomiting — and was admitted. “Enzyme deficiency,” Zembruski-Ruple texted a friend.

The 65-year-old, a patient advocate who had worked for the National Multiple Sclerosis Society and other groups, would never go home.

Covered in bruises and unable to swallow or talk, she eventually entered hospice care and died March 25 from the very drug that was supposed to extend her life, said her longtime partner, Richard Khavkine. Zembruski-Ruple was deficient in the enzyme that metabolizes capecitabine, the chemotherapy drug she took, said Khavkine and Susan Zembruski, one of her sisters. Zembruski-Ruple was among about 1,300 Americans each year who die from the toxic effects of that pill or its cousin, the IV drug fluorouracil known as 5-FU.

Doctors can test for the deficiency — and then either switch drugs or lower the dosage if patients have a genetic variant that carries risk. The FDA approved an antidote in 2015, but it’s expensive and must be administered within four days of the first chemotherapy treatment.

Newer cancer drugs sometimes include a companion diagnostic to determine whether a drug works with an individual patient’s genetics. But 5-FU went on the market in 1962 and sells for about $17 a dose; producers of its generic aren’t seeking approval for toxicity tests, which typically cost hundreds of dollars. Doctors have only gradually understood which gene variants are dangerous in which patients, and how to deal with them, said Alan Venook, a colorectal and liver cancer specialist at the University of California-San Francisco.

By the time Zembruski-Ruple’s doctors told her she had the deficiency, she had been on the drug for eight days, said Khavkine, who watched over his partner with her sister throughout the seven-week ordeal.

Khavkine said he “would have asked for the test” if he had known about it, but added “nobody told us about the possibility of this deficiency.” Zembruski-Ruple’s sister also said she wasn’t warned about the fatal risks of the chemo, or told about the test.

“They never said why they didn’t test her,” Zembruski said. “If the test existed, they should have said there is a test. If they said, ‘Insurance won’t cover it,’ I would have said, ‘Here’s my credit card.’ We should have known about it.”

Guidance Moves at a Glacial Pace

Despite growing awareness of the deficiency, and an advocacy group made up of grieving friends and relatives who push for routine testing of all patients before they take the drug, the medical establishment has moved slowly.

A panel of the National Comprehensive Cancer Network, or NCCN — specialists from Sloan Kettering and other top research centers — until recently did not recommend testing, and the FDA does not require it.

In response to a query from KFF Health News about its policy, Sloan Kettering spokesperson Courtney Nowak said the hospital treats patients “in accordance with NCCN guidelines.” She said the hospital would not discuss a patient’s care.

On Jan. 24, the FDA issued a warning about the enzyme deficiency in which it urged health care providers to “inform patients prior to treatment” about the risks of taking 5-FU and capecitabine.

On March 31 — six days after Zembruski-Ruple’s death — the network’s expert panel for most gastrointestinal cancers took a first step toward recommending testing for the deficiency.

Worried that President Donald Trump’s FDA might do nothing, Venook said, the panel — whose guidance shapes the practices of oncologists and health insurers — recommended that doctors consider testing before dosing patients with 5-FU or capecitabine.

However, its guidance stated that “no specific test is recommended at this time,” citing a lack of data to “inform dose adjustments.”

Sloan Kettering “will consider this guidance in developing personalized treatment plans for each patient,” Nowak told KFF Health News.

The new NCCN guidance was “not the blanket recommendation we were working toward, but it is a major step toward our ultimate goal,” said Kerin Milesky, a public health official in Brewster, Massachusetts, who’s part of an advocacy group for testing. Her husband, Larry, died two years ago at age 73 after a single treatment of capecitabine.

European drug regulators began urging oncologists to test patients for deficiency in May 2020. Patients with potentially risky genetics are started on a half-dose of the cancer drug. If they suffer no major toxicity, the dose is increased.

A Lifesaving Ultimatum?

Emily Alimonti, a 42-year-old biotech salesperson in upstate New York, chose that path before starting capecitabine treatment in December. She said her doctors — including an oncologist at Sloan Kettering — told her they didn’t do deficiency testing, but Alimonti insisted. “Nope,” she said. “I’m not starting it until I get the test back.”

The test showed that Alimonti had a copy of a risky gene variant, so doctors gave her a lower dose of the drug. Even that has been hard to tolerate; she’s had to skip doses because of low white blood cell counts, Alimonti said. She still doesn’t know whether her insurer will cover the test.

Around 300,000 people are treated with 5-FU or capecitabine in the United States each year, but its toxicity could well have prevented FDA approval were it up for approval today. Short of withdrawing a drug, however, U.S. regulators have little power to manage its use. And 5-FU and capecitabine are still powerful tools against many cancers.

At a January workshop that included FDA officials and cancer specialists, Venook, the NCCN panel’s co-chair, asked whether it was reasonable to recommend that doctors obtain a genetic test “without saying what to do with the result.”

But Richard Pazdur, the FDA’s top cancer expert, said it was time to end the debate and commence testing, even if the results could be ambiguous. “If you don’t have the information, how do you have counseling?” he asked.

Two months later, Venook’s panel changed course. The price of tests has fallen below $300 and results can be returned as soon as three days, Venook said. Doubts about the FDA’s ability to further confront the issue spurred the panel’s change of heart, he said.

“I don’t know if FDA is going to exist tomorrow,” Venook told KFF Health News. “They’re taking a wrecking ball to common sense, and that’s one of the reasons we felt we had to go forward.”

On May 20, the FDA posted a Federal Register notice seeking public input on the issue, a move that suggested it was considering further action.

Venook said he often tests his own patients, but the results can be fuzzy. If the test finds two copies of certain dangerous gene variants in a patient, he avoids using the drug. But such cases are rare — and Zembruski-Ruple was one of them, according to her sister and Khavkine.

Many more patients have a single copy of a suspect gene, an ambiguous result that requires clinical judgment to assess, Venook said.

A full-gene scan would provide more information but adds expense and time, and even then the answer may be murky, Venook said. He worries that starting patients on lower doses could mean fewer cures, especially for newly diagnosed colon cancer patients.

Power Should Rest With Patients

Scott Kapoor, a Toronto-area emergency room physician whose brother Anil, a much-loved urologist and surgeon, died of 5-FU toxicity at age 58 in 2023, views Venook’s arguments as medical paternalism. Patients should decide whether to test and what to do with the results, he said.

“What’s better — don’t tell the patient about the test, don’t test them, potentially kill them in 20 days?” he said. “Or tell them about the testing while warning that potentially the cancer will kill them in a year?”

“People say oncologists don’t know what to do with the information,” said Karen Merritt, whose mother died after an infusion of 5-FU in 2014. “Well, I’m not a doctor, but I can understand the Mayo Clinic report on it.”

The Mayo Clinic recommends starting patients on half a dose if they have one suspect gene variant. And “the vast majority of patients will be able to start treatment without delays,” Daniel Hertz, a clinical pharmacologist from the University of Michigan, said at the January meeting.

Some hospitals began testing after patients died because of the deficiency, said Lindsay Murray, of Andover, Massachusetts, who has advocated for widespread testing since her mother was treated with capecitabine and died in 2021.

In some cases, Venook said, relatives of dead patients have sued hospitals, leading to settlements.

Kapoor said his brother — like many patients of non-European origin — had a gene variant that hasn’t been widely studied and isn’t included in most tests. But a full-gene scan would have detected it, Kapoor said, and such scans can also be done for a few hundred dollars.

The cancer network panel’s changed language is disappointing, he said, though “better than nothing.”

In video tributes to Zembruski-Ruple, her friends, colleagues, and clients remembered her as kind, helpful, and engaging. “JoEllen was beautiful both inside and out,” said Barbara McKeon, a former colleague at the MS Society. “She was funny, creative, had a great sense of style.”

“JoEllen had this balance of classy and playful misbehavior,” psychotherapist Anastatia Fabris said. “My beautiful, vibrant, funny, and loving friend JoEllen.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Subscribe to KFF Health News’ free Morning Briefing.

This article first appeared on KFF Health News and is republished here under a Creative Commons license.