DNA tests of Lassa virus mid-outbreak helped Nigeria target its response

When an outbreak of a viral hemorrhagic fever hit Nigeria in 2018, scientists were ready: They were already in the country testing new disease-tracking technology, and within weeks managed to steer health workers toward the most appropriate response.

Lassa fever, which is transmitted from rodents to humans, pops up every year in West Africa. But 2018 was the worst season on record for Nigeria. By mid-March, there were 376 confirmed cases — more than three times as many as by that point in 2017 — and another 1,495 suspected. Health officials weren’t sure if the bad year was being caused by the strains that usually circulate, or by a new strain that might be more transmissible between humans and warrant a stronger response.
New technology for analyzing DNA in the field helped answer that question mid-outbreak, confirming the outbreak was being caused by pretty much the same strains transmitted from rodents to humans in past years. That rapid finding helped Nigeria shape its response, allowing health officials to focus efforts on rodent control and safe food storage, rather than sinking time and money into measures aimed at stopping unlikely human-to-human transmission, researchers report in the Jan. 4 Science.

While the scientists were reporting their results to the Nigeria Centre for Disease Control, they were also discussing the data with other virologists and epidemiologists in online forums. This kind of real-time collaboration can help scientists and public health workers “see the bigger picture about pathogen spread,” says Nicholas Loman, a microbial genomicist at the University of Birmingham in England who was not involved in the research.

Portable DNA sequencers, some as small as a cell phone, have allowed scientists to read the genetic information of viruses emerging in places without extensive lab infrastructure. Looking for genetic differences between patient samples can give clues to how a virus is being transmitted and how quickly it’s changing over time — key information for getting outbreaks under control. If viral DNA from several patients is very similar, that suggests the virus may be transmitted between people; if the DNA is more distinct, people might be picking up the virus independently from other animals.

The technology has also been used amid recent Ebola and Zika outbreaks. But the Lassa virus presents a unique challenge, says study coauthor Stephan Günther, a virologist at the Bernhard-Nocht-Institute for Tropical Medicine in Hamburg, Germany. Unlike Ebola or Zika, Lassa has a lot of genetic variation between strains. So while the same small regions of DNA from various strains of Ebola or Zika can be identified for analysis, it’s hard to accurately target similar regions for comparison among Lassa strains.
Instead, Günther and his team used a tactic called metagenomics: They collected breast milk, plasma and cerebrospinal fluid from patients and sequenced all the DNA within — human, viral and anything else lurking. Then, the team picked out the Lassa virus DNA from that dataset.

All told, the scientists analyzed Lassa virus DNA from 120 patients, far more than initially intended. “We went to the field to do a pilot study,” Günther says. “Then the outbreak came. And we quickly scaled up.” Preexisting relationships in Nigeria helped make that happen: The team had been collaborating for a decade with researchers at the Irrua Specialist Teaching Hospital and working alongside the World Health Organization and the Nigeria Centre for Disease Control.

Analyzing and interpreting the massive amounts of data generated by the metagenomics approach was a challenge, especially with limited internet connection, Günther says. Researchers analyzed 36 samples during the outbreak — less than a third of their total dataset, but still enough to guide the response. The full analysis, completed after the outbreak, confirmed the initial findings.

A metagenomics approach could be useful in disease surveillance more broadly. Currently, “we look for things that we know about and expect to find. Yet evidence from Ebola in West Africa and Zika in the Americas is that emerging pathogens can pop up in unexpected places, and take too long to be recognized,” Loman says. Sequencing all DNA in a sample, he says, could allow scientists to detect problem pathogens before they cause outbreaks.Instead, Günther and his team used a tactic called metagenomics: They collected breast milk, plasma and cerebrospinal fluid from patients and sequenced all the DNA within — human, viral and anything else lurking. Then, the team picked out the Lassa virus DNA from that dataset.

All told, the scientists analyzed Lassa virus DNA from 120 patients, far more than initially intended. “We went to the field to do a pilot study,” Günther says. “Then the outbreak came. And we quickly scaled up.” Preexisting relationships in Nigeria helped make that happen: The team had been collaborating for a decade with researchers at the Irrua Specialist Teaching Hospital and working alongside the World Health Organization and the Nigeria Centre for Disease Control.

Analyzing and interpreting the massive amounts of data generated by the metagenomics approach was a challenge, especially with limited internet connection, Günther says. Researchers analyzed 36 samples during the outbreak — less than a third of their total dataset, but still enough to guide the response. The full analysis, completed after the outbreak, confirmed the initial findings.

A metagenomics approach could be useful in disease surveillance more broadly. Currently, “we look for things that we know about and expect to find. Yet evidence from Ebola in West Africa and Zika in the Americas is that emerging pathogens can pop up in unexpected places, and take too long to be recognized,” Loman says. Sequencing all DNA in a sample, he says, could allow scientists to detect problem pathogens before they cause outbreaks.

Satellites make mapping hot spots of ammonia pollution easier

Satellites may be a more accurate way to track smog-producing ammonia.

It’s notoriously tricky to pinpoint accurate numbers for ammonia gas emissions from sources such as animal feedlots and fertilizer plants. But new maps, generated from infrared radiation measurements gathered by satellites, reveal global ammonia hot spots in greater detail than before. The new data suggest that previous estimates underestimate the magnitude of these emissions, researchers report December 5 in Nature.

In the atmosphere, ammonia, which contains nitrogen, can help form tiny particles that worsen air quality and harm human health. The research could help keep tabs on who’s emitting how much, to make sure that factories and farms are meeting environmental standards.
Emissions are usually estimated by adding up output from individual known sources of activity, but those calculations are only as good as the data that go into them. Ammonia sticks around only hours to a few days in the atmosphere, so on-the-ground measurements vary a lot even in the same place, says coauthor Martin Van Damme, an atmospheric scientist at the Université Libre de Bruxelles in Belgium.

“There’s so much uncertainty in ammonia emissions,” says Daven Henze, a mechanical engineer at the University of Colorado Boulder who wasn’t part of the research. Other scientists, including his research group, have estimated ammonia releases using satellite data before. But these new maps rely on a more detailed dataset and have substantially better resolution, Henze says — fine enough that the study authors were able to link areas of high emissions to specific factories or farms.
The new maps show 248 nitrogen emission hot spots across the globe at a resolution of about a kilometer. Eighty-three of those hot spots arose from agricultural activity that involved high numbers of cows, pigs and chickens, such as a site in Colorado that overlapped on satellite imagery maps with two big cattle feedlots. Ammonia emissions from feedlots come largely from livestock waste. Another 158 sites were affected by industrial emissions — mostly from sites that produced ammonia-based fertilizer, such as in Marvdasht, Iran. Six hot spots couldn’t be pinned to specific activity.
Ammonia is also emitted naturally, from volcanoes or seabird colonies. But most of those sources were too weak or not concentrated enough to show up as hot spots in the data. Lake Natron in Tanzania is the one exception — its mud flats show up as an ammonia-releasing hot spot, perhaps due to decaying algae. But it’s not clear why other lakes with similar mud flats didn’t. Some natural sources may have gone undetected because of where they were located — in places with heavy cloud cover that obscured the data, or where turbulent air dissipated ammonia especially quickly, Van Damme suggests.

Some areas with particularly high overall ammonia emissions from biomass burning or fertilizer, such as West Africa and the Indus Valley in Pakistan and northern India, didn’t reveal specific hot spots, either, the researchers report.

High-speed video reveals physics tricks for shooting a rubber band

Scientists are taking aim at the physics of rubber band bombardments.

Using high-speed video, researchers have analyzed what happens to a rubber band when it’s launched from a thumb. The results offer some tips for how to make a clean shot, Boston University mechanical engineers Alexandros Oratis and James Bird report in a paper in press in Physical Review Letters.

The researchers focused on one particular shooting technique: Elastic is slung around the raised thumb of one hand and pulled back with the fingers of the other hand. Standardizing the operation by using a cylinder rather than a thumb, the scientists filmed the details of the shooting process.

When the rubber band is let loose, a release of tension in the band quickly travels toward the cylinder. Meanwhile, the band itself zings toward the cylinder at a slower speed than that tension release, the scientists found.

When shot off a thumb, the band’s forward motion could lead to a rubbery rear-ender, with the thumb getting in the way of the elastic and sending the band askew. But if the feat is performed properly, the release of tension causes the thumb to duck out of the way before the rubber band reaches it. The band then sails past, buckling into a wrinkly shape as it shoots by.

By testing different shooting strategies, the researchers zeroed in on some guidelines. Don’t pull the band too tight: The extra tension increases the flight speed, so the thumb doesn’t deflect fast enough to avoid it. And a wider elastic band is preferred. That’s because the thumb must exert more force against the wider band, so that when the band is released, the digit falls away more quickly, making the elastic’s getaway easier.

The oldest known astrolabe was used on one of Vasco da Gama’s ships

While searching for shipwreck remains near Oman in the Arabian Sea in 2014, divers discovered an unusual metal disk that has since proven to be the world’s oldest known mariner’s astrolabe, British researchers report.

The navigational device came from the wreckage of a ship in the Portuguese armada that had been part of explorer Vasco da Gama’s second voyage to India from 1502 to 1503. Historical decorations on the artifact led the researchers to suggest that the disk was used as early as 1496.
A bit wider than a dollar bill, the astrolabe contains carvings of Portugal’s royal coat of arms and a depiction of a ringed Earth that was associated with a Portuguese king who ruled from late 1495 to 1521. Laser imaging of the disk revealed 18 scale marks separated at 5-degree intervals.

The device, used to take altitudes at sea, could have measured from 0 degrees — when the sun is at the horizon — to 90 degrees — when the sun is directly overhead, the team reports in a study published online March 16 in the International Journal of Nautical Archaeology. Only one other solid disk, mariner’s astrolabe has been found, and its authenticity and age are uncertain, say oceanographer David Mearns and colleagues. Mearns directs Blue Water Recoveries in Midhurst, England, a company that locates and studies shipwrecks.

Of 104 artifacts known to have been used as mariner’s astrolabes, the new find is not only the oldest, but also the only one decorated with a national symbol, the researchers say. By the early 1500s, most navigators had adopted more precise, open-wheeled astrolabes.

U.S. fentanyl deaths are rising fastest among African-Americans

Since people in the United States began dying in the fentanyl-related drug overdose epidemic, whites have been hit the hardest. But new data released March 21 by the Centers for Disease Control and Prevention show that African-Americans and Hispanics are catching up.

Non-Hispanic whites still experience the majority of deaths involving fentanyl, a synthetic opioid. But among African-Americans and Hispanics, death rates rose faster from 2011 to 2016. Whites experienced a 61 percent annual increase, on average, while the rate rose 140.6 percent annually for blacks and 118.3 percent per year for Hispanics. No reliable data were available for other racial groups.
Overall, the number of U.S. fentanyl-related deaths in 2011 and 2012 hovered just above 1,600. A sharp increase began in 2013, reaching 18,335 deaths in 2016. That’s up from 0.5 deaths per 100,000 people in 2011 to 5.9 per 100,000 in 2016.

In the first three years of the data, men and women died from fentanyl-related overdoses at similar rates, around 0.5 per 100,000. But in 2013, those paths diverged, and by 2016, the death rate among men was 8.6 per 100,000; for women it was 3.1 per 100,000. Overdose death rates rose most sharply along the East Coast, including in New England and the middle Atlantic, and in the Great Lakes region.

One of the most powerful opioids, fentanyl has been around for decades and is still prescribed to fight pain. But it has emerged as a street drug that is cheap to make and is found mixed into other drugs. In 2013, fentanyl was the ninth most common drug involved in overdose deaths, according to the CDC report; in 2016, it was number one. Just a little bit can do a lot of damage: The drug can quickly kill a person by overwhelming several systems in the body (SN: 9/3/2016, p. 14).

Women have a new weapon against postpartum depression, but it’s costly

Approval of the first and only treatment in the United States specifically targeting postpartum depression offers hope for millions of women each year who suffer from the debilitating mental health disorder after giving birth.

The new drug brexanolone — marketed under the name Zulresso and approved on March 19 by the U.S. Food and Drug Administration — is expected to become available to the public in late June. Developed by Sage Therapeutics, based in Cambridge, Mass., the drug is costly and treatment is intensive: It’s administered in the hospital as a 60-hour intravenous drip, and a treatment runs between $20,000 and $35,000. But researchers say that it could help many of the estimated 11.5 percent of U.S. new moms each year who experience postpartum depression, which can interfere with normal bonding between mothers and infants and lead to feeling hopeless, sad or overly anxious.
Here’s a closer look at the drug, its benefits and some potential drawbacks.

How does the new drug work?
How exactly brexanolone works is not known. But because the drug’s chemical structure is nearly identical to the natural hormone allopregnanolone, it’s thought that brexanolone operates in a similar way.

Allopregnanolone enhances the effects of a neurochemical called gamma-aminobutyric acid, or GABA, which stops nerve cells in the brain from firing. Ultimately this action helps quell a person’s anxiety or stress.
During pregnancy, the concentration of allopregnanolone in a woman’s brain spikes. This leads some neurons to compensate by temporarily tuning out GABA so that the nerve cells don’t become too inactive. Levels of the steroid typically return to normal quickly after a baby is born, and the neurons once again responding to GABA shortly thereafter. But for some women, this process can take longer, possibly resulting in postpartum depression.

Brexanolone temporarily elevates the brain’s allopregnanolone levels again, which results in a patient’s mood improving. But it’s still not clear exactly why the drug has this effect, says Samantha Meltzer-Brody, a reproductive psychiatrist at the University of North Carolina School of Medicine in Chapel Hill and the lead scientist of the drug’s clinical trials. Nor is it clear whether allopregnanolone’s, and thus possible brexanolone’s, influence on GABA is affecting only postpartum depression. But the drug clearly “has this incredibly robust response,” she says, “unlike anything currently available.”

How effective was the drug in clinical trials?
Brexanolone went through three separate clinical trials in which patients were randomly given either the drug or a placebo: one Phase II trial, which tests the drug’s effectiveness and proper dosage, and two Phase III trials, which tested the drug’s effects on moderate or severe postpartum depression and were necessary to gain approval for the drug’s commercial use in people.

Of 234 people who completed the trials, 94 received the suggested dosage of brexanolone. About 70 of those patients, or 75 percent, had what Meltzer-Brody described as a “robust response” to just one course of treatment. And of those patients with positive responses, 94 percent continued to feel well 30 days after the treatment. The results suggest that the drug may be most effective for those with severe postpartum depression; among those with moderate symptoms, the drug and the placebo had a fairly similar impact.

Can people take the drug again?
“There’s nothing prohibiting” a second course of brexanolone, but the effects of a repeat course have not been studied, Meltzer-Brody says. The drug was designed to be taken in tandem with the start of antidepressants, which take effect after about two to four weeks. So by the time the brexanolone wears off, the antidepressants would have kicked in.

It’s not clear yet if some patients could need a second dose. The clinical trials compared a group of women taking both antidepressants and brexanolone with another group taking only brexanolone and found no difference in the two group’s response 30 days after tests ended, Meltzer-Brody says. Because the study ended at 30 days, it’s unclear if the effects of brexanolone on its own last longer.

Can women breastfeed while taking brexanolone?
As a precaution, treated women did not breastfeed until six days after taking the drug. But in tests of breastmilk from 12 treated, lactating women, concentrations of brexanolone in breastmilk were negligible — less than 10 nanograms per millileter — in most of the women 36 hours after they received the infusion, according to Sage’s briefing document for the FDA. The FDA has yet to issue guidance on breast feeding.

Are there side effects?
About a third of the trial patients experienced sleepiness, sedation or headaches. The possibility of drowsiness led to the FDA’s requirement that the drug be administered by IV drip in a supervised setting. “If someone isn’t supervised, then there would be the risk that someone could get sleepy and pass out,” Meltzer-Brody says.

Are there plans for different versions of the drug?
Sage Therapeutics is developing a pill version of a drug called SAGE-217. It’s chemically similar to brexanolone and has similar antidepressant effects. Early results from a Phase III trial reported by the company in January show that, of 78 women treated with the pill, 72 percent responded favorably within two weeks, and 53 percent had not experienced a recurrence of symptoms four weeks later.

Is it worth the price and time?
Setting aside 60 hours to be hospitalized for an expensive drug could be discouraging for some. “It’s going to be very important for insurance to cover it in order for it be accessible,” Meltzer-Brody says. “I’m hoping that will be the case.” But based on the reaction of women with severe postpartum depression who participated in the trials, “two-and-a-half days seems like nothing if your debilitating, depressive symptoms will be gone.”

The delight of discovering an asteroid that spits

These are wondrous times for space exploration. Just when you think exploring the cosmos couldn’t possibly get more fun, another discovery delivers a new “oh wow” moment.

Consider the asteroid Bennu. It’s an unprepossessing space rock that drew scientists’ curiosity because it is among the most pristine objects in our solar system, and it might provide clues to the origins of life. But checking out Bennu is no trip to Paris; it’s about 130 million kilometers from Earth. NASA launched its OSIRIS-REx probe to Bennu in 2016, and it didn’t arrive until last December. The spacecraft is currently orbiting its quarry in preparation for an attempt at gathering samples from the asteroid’s surface in 2020 and then toting them back to Earth. Estimated delivery date: September 24, 2023. Clearly, asteroid science is not a discipline for those with short attention spans.
So imagine scientists’ delight when OSIRIS-REx already had news to share: Bennu is squirting jets of dust into space. It’s an asteroid behavior no one had ever seen before. Astronomy writer Lisa Grossman learned all about Bennu’s surprise jets while attending the Lunar and Planetary Science Conference in March. She reports that the dusty fountains may be the work of volatile gases beneath Bennu’s surface. The presence of volatiles would suggest that the rock wandered into the inner solar system relatively recently. But astronomers still have a lot to figure out about Bennu’s history, and they couldn’t be happier.

In other surprising space rock news from the conference, astronomers analyzing the much-more-distant object dubbed Ultima Thule now think it’s an agglomeration of mini-worlds that stuck together in the early days of the solar system — as Grossman terms it, a “Frankenworld.” That’s just the latest unexpected news from this Kuiper Belt denizen. If you’re as space rock obsessed as we are, you may recall that the first fuzzy images from NASA’s New Horizons spacecraft, which flew by Ultima Thule on January 1, suggested that the rock looked like a bowling pin or a snowman spinning in space. More recent images reveal not a snowman, but instead two pancakes or hamburger patties glued end to end (SN: 3/16/19, p. 15). That has scientists scrambling to figure out what forces could create such an oddly shaped object.

We’ll be hearing more about Bennu, Ultima Thule and other residents of our solar system in the months to come. I’m particularly looking forward to news from the Parker Solar Probe, which is tightening its orbit around the sun. I’m the one who is going to have to be patient in this case, though that’s not an attribute typically associated with journalists. The spacecraft won’t make its closest encounter with the sun until 2024, before ending its mission the following year. But the probe will be reporting in, and we’ll be reporting, too, as it makes this historic journey (SN: 1/19/19, p. 7).

Open your Web browser or your trusty print magazine and join us for the adventure. We hope you’ll enjoy the journey as much as we do.

50 years ago, scientists were unlocking the secrets of bacteria-infecting viruses

Unusual virus is valuable tool —

Viruses, which cannot reproduce on their own, infect cells and usurp their genetic machinery for use in making new viruses…. But just how viruses use the cell machinery is unknown.… Some answers may come from work with an unusual virus, called M13, that has a particularly compatible relationship with … [E. coli] bacteria. — Science News, April 5, 1969

Update
M13 did help unlock secrets of viral replication. Some bacteria-infecting viruses, called bacteriophages or simply phages, kill the host cell after hijacking the cell’s machinery to make copies of themselves. Other phages, including M13, leave the cell intact. Scientists are using phage replication to develop drugs and technologies, such as virus-powered batteries (SN: 4/25/09, p. 12). Adding genetic instructions to phage DNA for making certain molecules lets some phages produce antibodies against diseases such as lupus and cancer. The technique, called phage display, garnered an American-British duo the 2018 Nobel Prize in chemistry (SN: 10/27/18, p. 16).

Testing mosquito pee could help track the spread of diseases

There are no teensy cups. But a urine test for wild mosquitoes has for the first time proved it can give an early warning that local pests are spreading diseases.

Mosquito traps remodeled with a pee-collecting card picked up telltale genetic traces of West Nile and two other worrisome viruses circulating in the wild, researchers in Australia report April 4 in the Journal of Medical Entomology.

The tests were based on an innovative saliva monitoring system unveiled in 2010: traps that lure mosquitoes into tasting honey-coated cards. Among its advantages, this card-based medical testing doesn’t need the constant refrigeration that checking whole mosquitoes does. And it’s not as labor intensive as monitoring sentinel chickens or pigs for signs of infection.
But testing traces of mosquito saliva left on these cards comes close to the limits of current molecular methods for detecting viruses. In part, it’s an issue of volume. A mosquito drools fewer than five nanoliters of saliva when it tastes a card. In comparison, mosquitoes excrete about 1.5 microliters of liquid per pee, offering a veritable flood of material. So Dagmar Meyer of James Cook University in Cairns, Australia and her colleagues created urine collectors using standard overnight light traps and longer-standing traps that exhale delicious carbon dioxide, a mosquito come-hither.

The team set out 29 urine traps in two insect-rich spots in Queensland along with traps equipped to catch mosquito saliva. When mosquitoes fell for the trick and entered a urine trap, their excretions dripped through a mesh floor onto a collecting card. Adding a moist wick of water kept trapped mosquitoes alive and peeing longer, thus improving the sample. Pee traps picked up three viruses — West Nile, Ross River and Murray Valley encephalitis — while the saliva ones detected two, the researchers report.

Toddlers tend to opt for the last thing in a set, so craft your questions carefully

My youngest child, now just over a year old, has started to talk. Even though I’ve experienced this process with my older two, it’s absolutely thrilling. He is putting words to the thoughts that swirl around in his sweet little head, making his mind a little less mysterious to the rest of us.

But these early words may not mean what we think they mean, a new study hints. Unsurprisingly, when 2-year-olds were asked a series of “this or that” questions, the toddlers showed strong preferences — but not for the reasons you’d think. Overwhelmingly, the toddlers answered the questions with the last choice given.
That bias, described in PLOS ONE on June 12, suggests that young children’s answers to these sorts of questions don’t actually reflect their desires. Instead, kids may simply be echoing the last thing they heard.

This verbal quirk can be used by parents to great effect, as the researchers point out in the title of their paper: “Cake or broccoli?” More fundamentally, the results raise questions about what sort of information a verbal answer actually pulls out of a young child’s mind. This murkiness is especially troublesome when it comes to questions whose answers call for adult action, such as: “Did you hit your sister on purpose or on accident?”

In the first series of experiments, researchers led by Emily Sumner at the University of California, Irvine, asked 24 1- and 2-year-olds a bunch of two-choice questions, some of which involved a polar bear named Rori or a grizzly bear named Quinn. One question, for example, was, “Does Rori live in an igloo or a tepee?” Later, the researchers switched the bear and the order of the options, asking, for example, “Does Quinn live in a tepee or an igloo?”

The toddlers could answer either verbally or, for reluctant speakers, by pointing at one of two stickers that showed the choices. When the children answered the questions by pointing, they chose the second option about half the time, right around chance. But when the toddlers spoke their answers, they chose the second option 85 percent of the time, regardless of the bear.
SECOND BEST A toddler taking part in a study selects the second option in three either-or questions. This tendency, called the recency bias, may reflect kids’ inability to juggle several choices in their minds simultaneously. Credit: E. Sumner et al/PLOS ONE 2019

This abundance of second options selected — a habit known as the recency bias — might be due to the fact that young children have trouble holding the first option in mind, the researchers suspect. Other experiments showed that children’s tendency toward the second option got stronger when the words got longer.

Adults actually have the opposite tendency: We’re more inclined to choose the first option we’re given (the primacy bias). To see when this shift from last to first occurs, the researchers studied transcripts of conversations held between adults and children ages 1.5 to 4. In these natural conversations, 2-year-olds were more likely to choose the second option. But 3- and 4-year-olds didn’t show this bias, suggesting that the window closes around then.

The results hold a multitude of delightful parenting hacks: “Would you like to jump on the bed all night, or go to sleep?” But more importantly, the study serves as a reminder that the utterances of small children, while fascinating, may not carry the same meanings as those that come from more mature speakers. If you really want a straight answer, consider showing the two options to the toddler. But if you go that route, be prepared to hand over the cake.