State govt to test efficacy of antiviral Favipiravir for treatment of Covid patients

A health department official said, “The health minister issued a direction to rope in a team of doctors for assessing the effectiveness of Favipiravir on Covid patients.”

TNN August 24, 2020.

 

JAIPUR: The health department has issued directions to find out about the efficacy of antiviral drug Favipiravir used for treatment of Covid-19 patients.

A health department official said, “The health minister issued a direction to rope in a team of doctors for assessing the effectiveness of Favipiravir on Covid patients.”

A lot of pharmaceutical companies have rolled out Favipiravir with different brand names and have claimed it to be effective for treatment of Covid patients.

In Cities Where It Once Reigned, Heroin Is Disappearing

The rise of the more potent fentanyl in its place has put a generation of older users, who had managed their addiction, at far greater risk of overdose.

-By Abby Goodnough - NYT

William Glen Miller Sr. has been using heroin since he was 13 years old. He lost one leg to a heroin-related infection and now lives in a nursing home in Baltimore.CreditCreditLexey Swall for The New York Times

BALTIMORE — Heroin has ravaged this city since the early 1960s, fueling desperation and crime that remain endemic in many neighborhoods. But lately, despite heroin’s long, deep history here, users say it has become nearly impossible to find. 

Heroin’s presence is fading up and down the Eastern Seaboard, from New England mill towns to rural Appalachia, and in parts of the Midwest that were overwhelmed by it a few years back. It remains prevalent in many Western states, but even New York City, the nation’s biggest distribution hub for the drug, has seen less of it this year.

The diminishing supply should be a victory for public health and law enforcement alike. Instead, in cities like Baltimore, longtime users who managed to survive decades injecting heroin are now at far higher risk of dying from an overdose. That is because synthetic fentanyl, a deadlier drug that is much cheaper to produce and distribute than heroin, has all but replaced it.

The dramatic rise of fentanyl, which can be 50 times stronger than heroin, has been well documented. But its effect on many older, urban users of heroin, who had been able to manage their addiction for years, has been less noticed. The shift from heroin to fentanyl in cities has contributed to surging overdose deaths among older people and African-Americans and deeply unnerved many like William Glen Miller Sr., who first tried heroin as a 13-year-old in West Baltimore. 

“It doesn’t take a second for it to hit you,” said Mr. Miller, 64, describing the unfamiliar punch of fentanyl. “All I remember is pushing in the needle, and three hours later I am getting up off the ground.”

He was speaking from a nursing home bed in northern Baltimore, where he spent several recent months recovering from pneumonia and contemplating addiction treatment in another state. Heroin had a lulling effect, he and others said, but fentanyl is killing many of their peers. The claim is backed by federal data showing that the rate of overdose deaths involving fentanyl increased by nearly 54 percent in 2017 for people ages 55 to 64 — more than for any other age group.

“Clients we’ve known for years are dying,” said Derrick Hunt, director of the Baltimore City Needle Exchange Program, which has two vans that serve 17 locations around the city. “Everywhere I go, this person passed, that person passed.”

Lina Imbragulio, center, and her wife, Alissa Imbragulio, right, seek help from a Baltimore Health Department needle exchange van last month. “It doesn’t make you nod or give you that rush, even sniffing it,” Alissa said of fentanyl. “It just makes you tired.”CreditLexey Swall for The New York Times

The reason fentanyl is everywhere is economic: Dealers and traffickers can make far more money from it than from heroin. Instead of waiting months for poppy fields to grow in Mexico and farmers to harvest the brownish-black gum, which then gets refined into powder and shipped north, traffickers here and in Mexico can order fentanyl from China, or precursor chemicals to make it in clandestine labs, generating far more doses with far less labor.

This is not an elegy for heroin, a dangerous drug in its own right that spread from cities into suburbs and rural areas about a decade ago, when addictive prescription painkillers became harder to get. But for longtime urban users like Mr. Miller, many of them African-American, its disappearance is taking a particular toll. From 2016 to 2017, the fatal overdose rate from fentanyl and other synthetic opioids increased by 61 percent among black Americans, compared with a 45 percent increase for whites. 

The number of overdose deaths involving heroin has been dropping, even as overdose deaths over all have kept climbing because of fentanyl. In Maryland, deaths involving heroin fell by 38 percent from 2016 through 2018, according to preliminary data. In Massachusetts, heroin or likely heroin was present in 71 percent of opioid-related deaths in 2014; in the third quarter of 2018, it was present in only 34 percent. 

And in New Hampshire, which did not have a robust heroin market until the painkiller-fueled crisis of the past decade, the drug has almost completely vanished. Only four of the 397 opioid deaths in New Hampshire last year involved heroin, according to preliminary data; 363 involved fentanyl.

“In this situation, heroin looks protective compared to the fentanyl,” said Dr. Daniel Ciccarone, a family physician and researcher at the University of California, San Francisco, who has studied both drugs.

Nationally, there were 7 percent fewer deaths involving heroin in the year ending in September 2018 than there were in the previous year, according to preliminary data from the Centers for Disease Control and Prevention. The smaller overall decline may be a reflection of heroin’s continued strong presence in Western states like California and Arizona. 

Data on drug seizures similarly suggest a diminishing of heroin. Here in Baltimore, Todd C. Edwards, a spokesman for the Drug Enforcement Administration’s local district office, said law enforcement was now seizing more fentanyl than heroin. And in a Philadelphia neighborhood called Kensington, which has been hit particularly hard by opioid addiction, users report that “they can’t find heroin anymore,” said Patrick Trainor, a spokesman for the D.E.A. there. “It’s pretty much been replaced.”

On a street corner in East Baltimore one recent morning, a van distributed clean needles to about 25 clients, most of them older black men. Some leaned on canes or walkers; all said they missed heroin and its relative predictability. On the front of the van was a sticker showing a needle aimed at an arm and the words “GO SLOW,” a warning to inject only a little fentanyl at a time.

Each person took a paper bag full of needles and Narcan, the overdose reversal drug. The vans now also offer test strips, which people can use to check their drugs, including cocaine, for fentanyl. But some clients don’t see the point.

“Most people, they’re not using no test strips,” said Mr. Miller, who helped start a local group that hands out fentanyl strips and naloxone. “Because fentanyl is in daggone everything now.”

Fentanyl may still be mixed with heroin or other drugs, but increasingly, it arrives pure — either as powder or pressed into counterfeit pills resembling Percocet or Xanax. It can be diluted with more filler than heroin can, because it takes far less fentanyl to have a powerful effect.

“At the dealer level right now, fentanyl is like a magic dust it’s a moneymaker,” said Jon DeLena, the associate special agent in charge of the D.E.A.’s New England field division. 

“We were hearing people start to say, ‘I want the old stuff again, I want the brown,’ meaning heroin,” he continued. “But traffickers just started mixing fentanyl with something that had a brown tinge to it. They’re never, ever, ever going to go back to selling heroin around here again.”

Mexican poppy cultivation reached a high in 2017, according to the D.E.A. But several news outlets have reported that the price of opium paste the part of the poppy that gets turned into heroin — has dropped sharply over the last year, a sign that criminal organizations are increasingly focused on fentanyl.

Ray Donovan, who leads the D.E.A.’s New York office, said he believed China’s recent decision to ban all variants of fentanyl as a class could ultimately force traffickers to refocus on heroin. But because China has not banned many of the precursor chemicals needed to make fentanyl, others believe the effect could be minimal.

Tino Fuentes, a former heroin user who teaches people how to test their drugs for fentanyl, said only half of the samples he tests in New York these days are positive for heroin much less than even a year ago. 

“I have people telling me all the time, ‘If you find something that’s heroin, let me know,’” Mr. Fuentes said. 

Still, law enforcement officials are continuing to seize heroin coming across the border. From January through April, Customs and Border Protection officers seized 1,585 pounds of heroin at official ports of entry, along with 921 pounds of fentanyl. 

“The notion that heroin is disappearing altogether is false,” said Katherine Pfaff, a spokeswoman for the D.E.A., adding that the drop in heroin-related deaths could be a result of Narcan saving more heroin users. Still, she said, there is definitely more demand now for fentanyl than heroin in some regions, including New England. 

That could be because most users in those regions took up heroin only after crackdowns on prescribing opioids took hold, and were just as happy with fentanyl, Mr. DeLena said.

Not so for Mr. Miller and many other longtime heroin users.

“I’d rather have the straight heroin from back in the day,” said Duane Coleman, 67, who was among those seeking needles from the health department van. “The fentanyl comes on you too strong. Thank God I’m still holding on.”

Even if heroin were to proliferate again, Mr. Miller said, the high it provided would not suffice for most users because the fentanyl they have gotten used to is so much more potent. Mr. Miller said he had had to use fentanyl 10 times a day to avoid withdrawal, up from two or three times a day for heroin.

At the Baltimore needle exchange, Wayne Hall, 65, accepted a handful of strips to test his drugs for fentanyl, along with his batch of clean needles. He had gone to the emergency room recently, he said, after injecting what he assumes was fentanyl. He had woken up trembling, with his heart racing.

“When I was doing heroin I never shook like that,” he said, leaning on a cane, his paper bag of supplies tucked under his arm. “I do miss it.”

A Rare Genetic Mutation Leads to Cancer. The Fix May Already Be in the Drugstore.

A common dietary supplement may help overcome mutations in the Pten gene. Should patients take it?

-By Gina Kolata - NYT

Kelley Oliver Douglass, left, with her daughter Maryn. Ms. Douglass has a genetic mutation that can cause a range of cancers. A new study suggests that indole-3-carbinol, commonly sold as a supplement, may help restore the gene’s activity.CreditCreditTodd Anderson for The New York Times

When Kelley Oliver Douglass got breast cancer, a genetic counselor posed an odd question: Do you and your children have trouble finding hats that fit?

They did, and that gave the counselor a clue to the source of the cancer: a mutation in a gene called Pten. 

In addition to increasing head circumference, this rare mutation markedly raises the risk for several cancers, including prostate and breast cancer (the lifetime risk in carriers is 85 percent), as well as autism and schizophrenia in some individuals.

Ms. Douglass, 51, of Mount Dora, Fla., and her children carry a Pten mutation. Now, researchers have stumbled on a way to counter it — and the treatment may be as close as the local drugstore.

In a study published on Thursday in the journal Science, researchers found evidence that a compound called indole-3-carbinol (i3c) blocks an enzyme that inhibits the activity of Pten. With the gene more active, patients with the mutation may be better protected against cancer. 

They could get more i3c simply by eating brussels sprouts, broccoli or other cruciferous vegetables. But to get enough, they’d have to eat a lot: six pounds of brussels sprouts a day — raw.

Yet i3c also is widely available as a dietary supplement, and experts are debating whether to embark on a clinical trial with it. 

The new study was done only in mice and in human cancer cells grown in Petri dishes. The findings only apply to Pten gene activity — there is little evidence for most of the other wild claims made for i3c by supplement makers.

Inherited Pten mutations are rare, striking one in 200,000. If the research holds up, however, it could be important to larger numbers of cancer patients. The mutation is not just inherited; the Pten gene is spontaneously mutated in many tumors. When that happens, the patient’s prognosis is poor. 

Pten activity is somewhat impaired in the vast majority of human cancers. A drug that reactivates the gene could help curb cancer growth. 

Dr. Mustafa Sahin, an expert on the Pten gene at Boston Children’s Hospital, called the new research a “tour de force study.” The result is “a paradigm shift in the field and very exciting in terms of its therapeutic implications,” Dr. Sahin, who was not involved in the research, wrote in an email. 

Dr. Pier Paolo Pandolfi, senior author of the paper and director of the cancer center at Beth Israel Deaconess Medical Center in Boston, has spent years trying to find a way to restore Pten activity. 

The gene governs production of an enzyme that stops cells from dividing too quickly, reducing the chances that cancers will form. With reduced activity in Pten, cells grow uncontrollably. 

Pten mutations do not completely halt the gene’s functions. Instead, the mutations tamp down the gene’s activity, so cells make less of the enzyme needed for orderly growth. 

But one of the hardest things for researchers to do is to find a way to increase, rather than turn off, a gene’s activity. Eventually, Dr. Pandolfi and his colleagues learned enough about the Pten system to reason that i3c might do the trick.

“We got lucky, or smart,” he said.

Dr. Pandolfi and his colleagues tested their treatment on human prostate cancer cells and in mice bred to develop prostate cancer. It worked: In the cells and in mice, i3c treatment resulted in fewer cancers, and those that arose were small and less deadly.

The findings, while intriguing, raise a difficult question for people with Pten mutations. 

Should they run to the drugstore and buy i3c, hoping it will lower their cancer risk? Should cancer patients who have developed Pten mutations do so?

Or should everyone wait for rigorous clinical trials with a pharmaceutical-grade version of i3c? 

Dr. Pandolfi has posed those questions to several patient advocacy groups. All agreed that a clinical trial is necessary. 

But some urged waiting for a drug company to make a more potent compound. If a trial with a supplement fails, no one will want to try again, some patients worry. 

Others want to go ahead immediately with a trial using an i3c compound made so its purity and potency are assured. 

Kristin Anthony, president and chief executive of Pten Foundation, has the gene mutation and so does her 16-year-old daughter. Wary of taking a drugstore supplement and hoping for the best, she is urging that experts begin a clinical trial now with a pure form of i3c. 

If the results are at all promising, she hopes a drug company might develop and test a more potent form.

For her part, Ms. Douglass is doing all she can to protect herself and her children from cancer. She had her unaffected breast removed prophylactically and also had a prophylactic hysterectomy. 

A CT scan found an early-stage kidney cancer, so she had part of her kidney removed. She has frequent colonoscopies to check for colon cancer and skin exams to look for melanoma. 

Her 20-year-old daughter will soon be having mammograms, as is recommended for young women with inherited Pten mutations.

“A clinical trial could literally change my children’s lives,” Ms. Douglass said. “I would totally enter a clinical trial.”

In the meantime, she said, “I will eat more broccoli.”

Citrus Farmers Facing Deadly Bacteria Turn to Antibiotics, Alarming Health Officials

In its decision to approve two drugs for orange and grapefruit trees, the E.P.A. largely ignored objections from the C.D.C. and the F.D.A., which fear that expanding their use in cash crops could fuel antibiotic resistance in humans.

-By Andrew Jacobs - NYT

ZOLFO SPRINGS, Fla. — A pernicious disease is eating away at Roy Petteway’s orange trees. The bacterial infection, transmitted by a tiny winged insect from China, has evaded all efforts to contain it, decimating Florida’s citrus industry and forcing scores of growers out of business.

In a last-ditch attempt to slow the infection, Mr. Petteway revved up his industrial sprayer one recent afternoon and doused the trees with a novel pesticide: antibiotics used to treat syphilis, tuberculosis, urinary tract infections and a number of other illnesses in humans.

“These bactericides give us hope,” said Mr. Petteway’s son, R. Roy, 33, as he watched his father treat the family’s trees, some of them 50 years old. “Because right now, it’s like we’re doing the doggy paddle without a life preserver and swallowing water.”

Since 2016, the Environmental Protection Agency has allowed Florida citrus farmers to use the drugs, streptomycin and oxytetracycline, on an emergency basis, but the agency is now significantly expanding their permitted use across 764,000 acres in California, Texas and other citrus-producing states. The agency approved the expanded use  despite strenuous objections from the Food and Drug Administration and the Centers for Disease Control and Prevention, which warn that the heavy use of antimicrobial drugs in agriculture could spur germs to mutate so they become resistant to the drugs, threatening the lives of millions of people.

The E.P.A. has proposed allowing as much as 650,000 pounds of streptomycin to be sprayed on citrus crops each year. By comparison, Americans annually use 14,000 pounds of aminoglycosides, the class of antibiotics that includes streptomycin.

Roy Petteway spraying orange groves with bactericides on his farm in Zolfo Springs, Fla.

The European Union has banned the agricultural use of both streptomycin and oxytetracycline. So, too, has Brazil, where orange growers are battling the same bacterial scourge, called huanglongbing, also commonly known as citrus greening disease.

“To allow such a massive increase of these drugs in agriculture is a recipe for disaster,” said Steven Roach, a senior analyst for the advocacy group Keep Antibiotics Working. “It’s putting the needs of the citrus industry ahead of human health.”

But for Florida’s struggling orange and grapefruit growers, the approvals could not come soon enough. The desperation is palpable across the state’s sandy midsection, a flat expanse once lushly blanketed with citrus trees, most of them the juice oranges that underpin a $7.2 billion industry employing 50,000 people, about 40,000 fewer than it did two decades ago. These days, the landscape is flecked with abandoned groves and scraggly trees whose elongated yellow leaves are a telltale sign of the disease.

Mr. Petteway says the antibiotics have helped bring many of his trees back to life.

“They used to have pneumonia, but now it’s like they have a cold,” he said, tugging on the waxy, bright green leaf of a tree thick with embryonic, gumball-size fruit.

A temporary approval of the drugs was issued under President Barack Obama, but in December, under President Trump, the E.P.A. gave final approval for a much broader use of oxytetracycline. The agency has also proposed the expanded use of streptomycin under similar terms.

The decision paves the way for the largest use of medically important antibiotics in cash crops, and it runs counter to other efforts by the federal government to reduce the use of lifesaving antimicrobial drugs. Since 2017, the F.D.A. has banned the use of antibiotics to promote growth in farm animals, a shift that has led to a 33 percent drop in sales of antibiotics for livestock.

The use of antibiotics on citrus adds a wrinkle to an intensifying debate about whether the heavy use of antimicrobials in agriculture endangers human health by neutering the drugs’ germ-slaying abilities. Much of that debate has focused on livestock farmers, who use 80 percent of antibiotics sold in the United States. 

Although the research on antibiotic use in crops is not as extensive, scientists say the same dynamic is already playing out with the fungicides that are liberally sprayed on vegetables and flowers across the world. Researchers believe the surge in a drug-resistant lung infection called aspergillosis is associated with agricultural fungicides, and many suspect the drugs are behind the rise of Candida auris, a deadly fungal infection.

Drug-resistant infections kill 23,000 Americans each year and sicken two million, according to the C.D.C. As more germs mutate, the threat is growing. With few new medicines in the pipeline, the United Nations says resistant infections could claim 10 million lives globally by 2050, exceeding deaths from cancer.

Antibiotics sprayed on crops can affect farm workers or people who directly consume contaminated fruit, but scientists are especially worried that the drugs will cause pathogenic bacteria in the soil to become resistant to the compounds and then find their way to people through groundwater or contaminated food. The other fear is that these bacteria will share their drug-resistant mechanisms with other germs, making them, too, impervious to other kinds of antibiotics.

In its evaluation for the expanded use of streptomycin, the E.P.A., which largely relied on data from pesticide makers, said the drug quickly dissipated in the environment. Still, the agency noted that there was a “medium” risk from extending the use of such drugs to citrus crops, and it acknowledged the lack of research on whether a massive increase in spraying would affect the bacteria that infect humans.

“The science of resistance is evolving and there is a high level of uncertainty in how and when resistance occurs,” the agency wrote.

Since its arrival in Florida was first confirmed in 2005, citrus greening has infected more than 90 percent of the state’s grapefruit and orange trees. The pathogen is spread by a tiny insect, the Asian citrus psyllid, that infects trees as it feeds on young leaves and stems, but the evidence of disease can take months to emerge. Infected trees prematurely drop their fruit, most of it too bitter for commercial use.

Officials say it is too early to know how many farmers will embrace the spraying of antibiotics. Interviews with a dozen growers and industry officials suggest many farmers are waiting to see whether the regimen is effective.

The E.P.A. acknowledged that the volume of spraying could soar if the scourge reaches California’s commercial orange groves. More than 1,000 trees in the Los Angeles basin, most of them in residential backyards, have been infected so far this year, a doubling from the same period last year.

“It’s just a matter of time,” said James Cranney, president of the California Citrus Quality Council. 

Jim Adaskaveg, a plant pathologist at the University of California, Riverside, who does consulting work for the California citrus council, supports using antibiotics in agriculture. He noted that the government has long approved use of smaller amounts of streptomycin and oxytetracycline to manage a destructive bacterial disease that infects apple and pear crops.

Because the E.P.A. prohibits their application 40 days before harvest, he said there was little chance consumers would ingest the drugs. “We’ve been safely using them for decades,” he said.

Taw Richardson, the chief executive of ArgoSource, which makes the antibiotics used by farmers, said the company has yet to see any resistance in the 14 years since it began selling bactericides. “We don’t take antibiotic resistance lightly,” he said. “The key is to target the things that contribute to resistance and not get distracted by things that don’t.”

Many scientists disagree with such assessments, noting the mounting resistance to both drugs in humans. They also cite studies suggesting that low concentrations of antibiotics that slowly seep into the environment over an extended period of time can significantly accelerate resistance. 

Scientists at the C.D.C. were especially concerned about streptomycin, which can remain in the soil for weeks and is allowed to be sprayed several times a season. As part of its consultation with the F.D.A., the C.D.C. conducted experiments with the two drugs and found widespread resistance to them. 

Although the Trump administration has been pressing the E.P.A. to loosen regulations, Nathan Donley, a senior scientist at the Center for Biological Diversity, said the agency’s pesticides office had a long track record of favoring the interests of chemical and pesticide companies. “What’s in the industry’s best interest will win out over public safety nine times out of 10,” he said.

A spokesman for the E.P.A. said the agency had sought to address the C.D.C.’s and F.D.A.’s concerns about antibiotic resistance by ordering additional monitoring and by limiting its approvals to seven years. 

Still, it remains unclear whether the drugs even work on crops. Graciela Lorca, a molecular biologist at the University of Florida and an expert on citrus greening, said she is not convinced. In the absence of peer-reviewed studies, she and other researchers have largely relied on anecdotal evidence from growers who have reported some improvement after applying the drugs.

“Right now it’s a desperate measure for sure,” she said.

One recent afternoon, Kenny Sanders drove through his groves of Valencia and Hamin oranges and pointed out ailing trees adorned with the strips of pink tape that mark them for destruction.

“That’s the kiss of death,” Mr. Sanders, a former rodeo performer and cattle rustler, said in a jaunty twang. “Used to be if you had 40 acres, you’d drive a Cadillac and send your kids to college. Not anymore.”

He said he tried using antibiotics for one season, but gave up after seeing little improvement. Cost, he added, was the main reason he didn’t continue spraying.

In the meantime, he and many other growers have embraced a range of remedies: tearing out trees at the first sign of disease and planting new stock bred to better withstand the bacteria. He also regularly feeds his trees a precision blend of micronutrients, a coddling he says helps them withstand the disease.

Roy Petteway does all of the above, too, but he believes that the spraying is worth the expense. Soft-spoken and contemplative, he considers himself a environmentalist and though he worries about antibiotic resistance, he puts his faith in the E.P.A. and its determination that the risks of spraying are minimal. He sees it as a stopgap measure that can help his trees survive until researchers develop disease-resistant stock or more effective treatments.

As a fourth-generation grower, Mr. Petteway has more pressing concerns than the relatively abstract threat of antibiotic resistance.

“These trees are our livelihood and our future,” he said. “And I’ve got to make sure all of this is here for my children and grandchildren.”

A New Ebola Vaccine Strategy in Africa: Smaller Doses

As violence makes it harder to reach stricken villages in Congo, experts plan to stretch supplies and to give the vaccine to everyone, not just contacts of victims.

- By Donald G. McNeil Jr. - NYT

Health workers burying an eleven-month-old child this week in Beni, Democratic Republic of Congo, where the death toll from Ebola has risen past 1,000.CreditCreditHugh Kinsella Cunningham/EPA, via Shutterstock

Confronting an Ebola outbreak spiraling out of control in the Democratic Republic of Congo, the World Health Organization announced plans on Tuesday to change its vaccination strategy, offering smaller doses and eventually introducing a second vaccine.

The outbreak, which has lasted nine months, has now claimed more than 1,000 lives. Rebel groups have attacked health care centers or medical teams on dozens of occasions, leading many relief organizations to withdraw from the area.

According to a W.H.O. official quoted by The Associated Press, 85 health workers have been killed or wounded since January.

Because driving to villages with Ebola victims is so risky, the agency intends to launch brief and unexpected “pop-up” vaccination campaigns in communities considered safe.

The W.H.O. also wants to shift to immunizing as many people in each target area as possible, instead of relying solely on its current tactic: “ring vaccinating” the immediate contacts of each known case, along with health care workers.

Before such a change is made, the Congolese government must accept the recommendations made Tuesday by a W.H.O. panel of experts. Dr. Jean-Jacques Muyembe, who heads Congo’s ethical review board, welcomed the recommendations and said he would work to see them implemented quickly.

Demand for the vaccine is increasing in the affected districts of eastern Congo, Dr. Muyembe said.

There have been contradictory reports from the area about acceptance of the vaccine. Some observers said villagers and even health workers were rejecting the vaccine.

Others said villagers were angry that the vaccine was given only to contacts of victims when everyone was afraid of the infection.

According to the W.H.O., more than 111,000 people have been vaccinated against Ebola since the outbreak began in August. To stretch supplies of the vaccine, made by Merck and known as rVSV-ZEBOV, the agency recommended switching to smaller doses.

Those at highest risk contacts of known Ebola cases, and their contacts — should get 0.5 milliliter of vaccine, which is half the dose currently used, the W.H.O. said. The dose was used in a 2015 trial in Guinea and found to be protective.

Everyone else at lower risk but willing to be vaccinated should get 0.2 milliliter, or one-fifth of the current dose, the W.H.O. said. It will take longer for them to build immunity against the virus, but they should be at least partially protected.

Even at the full 1.0 milliliter dose, it is unclear how long the Merck vaccine’s protection lasts. In October, the W.H.O. said some studies indicated the vaccine protected against Ebola for about one year.

In addition, the W.H.O. recommended rolling out a second vaccine made by Johnson and Johnson, currently known as Ad26.ZEBOV/MVA-BN.

(Preliminary vaccines are named with initials describing their ingredients. The Merck vaccine uses a recombinant vesicular stomatitis virus to deliver the vaccine to cells, while the Johnson and Johnson vaccine used an adenovirus. Both viruses can infect humans but are rendered harmless in the vaccines.)

A consortium, including the Coalition for Epidemic Preparedness, which develops vaccines against pandemic diseases, and the London School of Hygiene and Tropical Medicine, is planning how to safely roll out the new vaccine.

In This Doctor’s Office, a Physical Exam Like No Other

Genetic and molecular analysis of 109 volunteers turned up hidden health problems in about half of them. Critics say the approach amounted to ‘carpet-bombing’ the body.

-By Carl Zimmer - NYT

A colored scanning electron micrograph of human chromosomes. Dr. Michael Snyder of Stanford University believes that “deep profiles” of patients, including genetic sequencing, may provide early warning signs of disease. Credit Bio photo Associates/Science Source

To scientists like Michael Snyder, chair of the genetics department at Stanford University, the future of medicine is data lots and lots of data.

He and others predict that one day doctors won’t just take your blood pressure and check your temperature. They will scrutinize your genome for risk factors and track tens of thousands of molecules active in your body.

By doing so, the doctors of the future will identify diseases, and treat them, long before symptoms appear.

The approach has a number of critics, who say it will never be cost-effective and will instead lead to wild over treatment of anxious patients.

But on Wednesday, Dr. Snyder and his colleagues published a study suggesting that big data may succeed where conventional medicine fails.

In 109 volunteers whose bodies were closely tracked and analyzed, the researchers discovered a host of hidden conditions that required medical attention, including diabetes and heart disease.

“It turns out 53 out of 109 people learned something really, really important from doing these deep profiles,” Dr. Snyder said.

The research offers an unprecedented look at how common diseases may arise in different people along different molecular paths, said Ali Torkamani, director of genome informatics at Scripps Research Translational Institute, who was not involved in the new study.

Once doctors are able to record genetic activity in their patients, “then you could start thinking about more rational ways of intervening,” he added.

The new study is the result of a remarkable scientific journey.

For a decade, Dr. Snyder has been trying to learn everything he can about his own body, down to its molecular building blocks. He has turned himself into a big-data guinea pig.

First, he and his colleagues sequenced his genome. Dr. Snyder learned to his surprise that he had several mutations linked to diabetes. The team analyzed his blood over the course of 14 months, tracking 40,000 molecules.

In 2011, that monitoring revealed that Dr. Snyder was indeed developing diabetes. He started treating the condition, and his symptoms improved.

In 2012, when Dr. Snyder and his colleagues published a study describing these efforts, no one had seen anything quite like it.

Along with his genome (all his genes), Dr. Snyder published his transcriptome (the molecular signature of which of his genes were active), his proteome (all the new proteins his body produced), and his metabolome (all the molecules involved in his metabolism).

One colleague jokingly said that Dr. Snyder had produced something new: “the narciss-ome.”

Many scientists hailed it as a proof of principle for a new way of treating patients, an approach sometimes called precision medicine.

Dr. Snyder, chair of the genetics department at Stanford University. Intense genetic analysis turned up early signs of diabetes in the researcher. Credit Paul Sakuma/Stanford School of Medicine

By vacuuming up data with the latest technologies, doctors one day may produce a razor-sharp picture of each patient’s health, and then devise individualized treatments when illness appears.

It was a seductive prospect. When Dr. Snyder decided to launch a larger project, he had little trouble attracting 108 other volunteers.

He and his colleagues started by sequencing each subject’s genome and performing in-depth physicals. Every three months, the volunteers returned to Stanford to give blood, urine, stool and cheek swabs. Some wore continuous glucose monitors, and some wore heartbeat trackers on their wrists.

The initial exams revealed a number of conditions. Eighteen people were diagnosed with Stage II hypertension. One volunteer had full-blown diabetes, without having ever been diagnosed with pre-diabetes in conventional exams.

Genome sequencing also revealed medical insights. One subject who suffered recurring strokes turned out to be taking the wrong medication, thanks to a mutation that made the drug ineffective.

Other volunteers discovered they had mutations that may cause serious illness. One had a genetic variant linked to enlarged, weakened heart muscles. An imaging test revealed the volunteer’s heart was indeed defective.

The researchers then analyzed the data they gathered from each patient to determine their healthy baselines.

In standard medicine, researchers determine baselines by taking an average across thousands of people. But while the average body temperature, for example, is around 98.6 degrees, that doesn’t mean that it’s normal for a given individual.

Some people just run hot or cold. To determine whether a patient’s temperature change might indicate illness, a doctor needs an individualized baseline.

Dr. Snyder and his colleagues worked out healthy baselines for each patient not just for body temperature, but heart rate and balances of various proteins.

Some subjects veered from their baselines as they were struck by illnesses, the researchers found. One volunteer underwent such a shift before getting diagnosed with lymphoma.

“We were able to go back and see molecules that were clearly starting to rise months before the diagnosis and then dropped with treatment,” said Sophia Miryam Schüssler-Fiorenza Rose, an instructor in neurosurgery at Stanford who was the lead author of the study.

“We think these might be very valuable early markers of disease,” she said.

Nine volunteers developed diabetes, but they reached that diagnosis by different paths. The condition worsened in two volunteers as they gained weight, but seven developed diabetes without getting fat.

Some turned out to produce very little insulin; others produced enough insulin, but it failed to lower their levels of glucose.

“We learned that people are Type 2 diabetic in very different ways,” said Dr. Snyder.

Dr. Snyder and his colleagues argue that examining the genomes of patients and carefully tracking them will make people healthier. Doctors will be able to catch diseases earlier, and treat them more precisely.

But critics questioned whether Dr. Snyder’s big-data firehose will actually make patients healthier or just leave them floating in a sea of uncertainty and anxiety.

“They carpet-bomb the body with tests and basically assume that the discovery of everything they hit is beneficial,” said Dr. Henrik Vogt, a postdoctoral researcher at the University of Oslo. “But there may be lots of collateral damage they don’t consider.”

Dr. Vogt, an outspoken critic of precision medicine, also noted Dr. Snyder and his colleagues did not compare the outcomes of their volunteers to people who were getting standard medical care. The extra cost and effort might not have led to comparatively better health.

“It’s hard to know what the results mean,” Dr. Vogt said.

Those criticisms haven’t stopped scientists from starting up companies that offer “deep profiles” to people who are willing to foot the bill. Dr. Snyder, for example, co-founded a company called Q, which promises “a comprehensive picture of your health in 75 minutes or less.”

But precision medicine is proving to be a tough sell. In April, one well-financed start-up called Arivale abruptly shut down. “The cost of providing the service exceeds what our customers can pay for it,” the company announced.

Karen Meagher, a bioethicist at the Mayo Clinic who was not involved in the new study, cautioned that these are still early days for precision medicine.

She wondered if most patients could manage constant monitoring as well as Dr. Snyder’s volunteers. “Some people are going to be really overwhelmed by the technology,” Dr. Meagher said.

Dr. Vogt was even more skeptical.

“The approach is unlikely to work for people most in need those who are poor, are barely hanging on, and have other things to worry about than monitoring themselves constantly,” he said.

Tracking the biological workings of his own body for a decade has been enlightening for Dr. Snyder, but far from a panacea.

After learning he had diabetes in 2011, he managed to keep his blood sugar levels in check for three years. In 2014, he crossed back over the line again.

“It turns out I’m slow in releasing insulin,” he said. “We can see exactly where my defect is.”

That finding led one doctor to suggest Dr. Snyder take medications that boost the release of insulin. Another recommended a drug that helps expel sugar from the body.

Five years after his second diagnosis, he still has diabetes. For now, he is trying long walks after eating instead of new drugs.

“I like to only change one variable at a time, so I can understand what is going on,” he said.

Drug Prices Will Soon Appear in Many TV Ads

-By Glenn Thrush and Katie Thomas - NYT

Alex Azar, the secretary for health and human services, announced the change, which has been pushed by patient advocates.CreditCreditGabriella Demczuk for The New York Times

WASHINGTON — The Trump administration for the first time will require pharmaceutical companies to include the price of prescription drugs in television advertisements if the cost exceeds $35 per month.

The move, announced on Wednesday by Alex M. Azar II, the health and human services secretary, is the most visible action the administration has taken so far to address the rising cost of prescription drugs. It has been a key issue for American voters and one that both Republicans and Democrats have vowed to address.

The proposal could be challenged by the drug industry, which argues that revealing the list price will confuse consumers and could violate the companies’ First Amendment rights. While the list price of some drugs can be thousands of dollars a month, patients with insurance that covers their prescriptions frequently pay far less, often less than $50.

“We are moving from a system where people are left in the dark to a system where patients are put in the driver’s seat,” Mr. Azar said in a conference call with reporters.

In ads, drug companies have been required to provide a list of potential side effects. Under the new guidelines expected to take effect this summer all direct-to-consumer television advertisements for drugs covered by Medicare or Medicaid must include the list price, also known as the wholesale acquisition price, in their ads, Mr. Azar said.

A disclaimer will also state, “if you have insurance that covers drugs, your cost may be different,” according to officials at the Department of Health and Human Services.

Drug makers must update the price they disclose every quarter, which will be the product’s monthly cost or the price for a course of treatment if it is not a chronic medication. The disclosure must be in “legible” text at the end of the advertisement, much like the list of side effects.

The move has been pushed by patient advocacy groups, which have complained that televised drug ads amounting to about $4 billion of the $5 billion spent by the industry on product promotion steer patients to high-priced medications or drugs they do not need.

Many of the most heavily advertised drugs cost thousands of dollars per month. Two dosing pens of AbbVie’s Humira, which treats rheumatoid arthritis and other conditions, have an average retail price of $5,684, according to the website GoodRx, which tracks drug prices. Another frequently advertised drug, Xeljanz, a Pfizer arthritis medication, costs about $4,840 a month.

The measure was applauded by Senators Richard Durbin of Illinois, a Democrat, and Charles Grassley of Iowa, a Republican, who together have tried to pass similar legislation. “Direct-to-consumer prescription drug advertisements are everywhere, and they tell you just about everything imaginable about the drug, other than its price,” the senators said in a joint statement. “We believe American patients deserve transparency.”

The drug industry has pointed out that many patients with insurance coverage pay far less than the list price. “We are concerned that the administration’s rule requiring list prices in direct-to-consumer (DTC) television advertising could be confusing for patients and may discourage them from seeking needed medical care,” said Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, the industry trade group.

On Wednesday, the lobbying group announced it had set up a website that would link patients to financial assistance for drugs as well as to company websites that provide data on list prices, typical out-of-pocket costs and sources of financial assistance.

The manufacturer Johnson & Johnson said this year that its ads would begin disclosing the list price, starting with those for the anti-stroke drug Xarelto that carries a $448 monthly list price, along with information about the typical consumer co-payment.

“If you’re ashamed of your drug prices, change your drug prices,” said Mr. Azar, who was a top executive with pharmaceutical giant Eli Lilly and Company before joining the Trump administration in January 2018. “It’s that simple.”

He compared the new requirement to a similar one for the automobile industry. “We have for over 50 years required that car manufacturers and car dealers post the sticker price of cars on the windows of their cars, and be transparent about that,” Mr. Azar said. “It’s a starting point.”

The new rule, he added, could prompt drug companies to lower their costs out of fear consumers would reject their products based on sticker shock alone.

Mr. Azar said he expected enforcement of the rule to come from the industry itself, from competing drug companies who sue those who do not comply for deceptive trade practices. If a drug company failed to disclose its price, it would be implicitly suggesting its product costs less than $35 a month, he said.

The change is part of a four-part plan by H.H.S. to tackle the issue of rising drug prices. It comes as House Democrats prepare to pass as many as a dozen health care bills, including several intended to lower drug prices, ahead of the 2020 campaign.

Democrats credit their victory in the 2018 midterm elections, in part, to a focus on health care, including preserving the Affordable Care Act.