Emerging Infections

Health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was confirmed in a 3-year-old girl in the capital, Lilongwe. It was the first case in Africa in 5 years, according to the World Health Organization.

Globally, there were only five cases of wild poliovirus in 2021, the WHO states.

“As long as wild polio exists anywhere in the world all countries remain at risk of importation of the virus,” Matshidiso Moeti, MBBS, WHO regional director for Africa, said in the statement.
 

Girl paralyzed in November

The Global Polio Eradication Initiative (GPEI) said in a statement that the 3-year-old girl  experienced paralysis in November, and stool specimens were collected. Sequencing of the virus was conducted in February, 2022, by the National Institute for Communicable Diseases in South Africa, and the Centers for Disease Control and Prevention confirmed the case as WPV1.

According to the WHO announcement, laboratory analysis shows that the strain identified in Malawi is linked to one circulating in Sindh Province in Pakistan. Polio remains endemic only in Afghanistan and Pakistan.

Kacey C. Ernst, PhD, MPH, professor and infectious disease epidemiologist at the University of Arizona’s Zuckerman College of Public Health in Tucson, pointed out that what is not clear from the press release is whether the girl had traveled to Pakistan or was infected in Malawi.

“This is a very significant detail that would indicate whether or not transmission was actively occurring in Malawi. Until that information is released, it is hard to judge the extent of the possible outbreak,” she said in an interview. “The good news is that this case was in fact detected. The surveillance systems are in place and they were able to identify wild-type cases.”

Dr. Ernst said that although there is cause for concern, it is “not a reason to panic. Malawi has very high polio vaccination rates and it is quite possible that this will be a very small defined outbreak that will be well contained.”

She added that the medical community should be alerted that this case has been identified so travelers who have been to affected areas who have any symptoms can be appropriately screened.

The WHO said it is helping Malawi health authorities in the response, including increasing immunizations.

However, a vaccination campaign comes at a time of health system upheaval in Malawi.

“Malawi, like countries all over the world, has seen an interruption in services due to COVID,” Joia S. Mukherjee, MD, MPH, chief medical officer with Partners in Health and associate professor with the division of global health equity at Brigham and Women’s Hospital and in the department of global health and social medicine at Harvard Medical School, Boston, said in an interview. “In addition, Malawi is currently dealing with the aftermath of a cyclone – where nearly a million people were displaced. Vaccination campaigns work best if there is solid infrastructure. Both COVID and the impact of climate change have shaken the health system.”

UN health agencies warned last year that millions of children who have not received immunizations during the pandemic, especially in Africa, “are now at risk from life-threatening diseases such as measles, polio, yellow fever, and diphtheria,” Reuters reported.

Africa was certified as wild poliovirus free on Aug. 25, 2020. The CDC had served as the lead partner over 3 decades in helping Africa reach the milestone. Africa will retain that status, the WHO stated, because the strain originated in Pakistan.

Five of six WHO regions have been certified polio free. The Americas received eradication certification in 1994.

There is no cure for polio, which can cause irreversible paralysis within hours, but the disease has been largely eradicated globally with an effective vaccine.
 

GPEI sending teams

The GPEI is sending a team to Malawi to support emergency operations, communications, and surveillance. Partner organizations will also send teams to support operations and innovative vaccination campaign solutions.

GPEI was launched in 1988 with the combined efforts of national governments, WHO, Rotary International, the CDC, and UNICEF. The GPEI partnership has included the Bill & Melinda Gates Foundation and, in recent years, Gavi, the Vaccine Alliance.

The CDC states, “[G]lobal incidence of polio has decreased by 99.9% since GPEI’s foundation. An estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive, whose lives would otherwise have been lost. Now the task remains to tackle polio in its last few strongholds and get rid of the final 0.1% of polio cases.”
 

Three wild poliovirus strains

There are three wild poliovirus strains: type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3).

“Symptomatically, all three strains are identical, in that they cause irreversible paralysis or even death. But there are genetic and virologic differences which make these three strains three separate viruses that must each be eradicated individually,” according to WHO.

WPV3 is the second strain to be wiped out, following the certification of the eradication of WPV2 in 2015.

A version of this article first appeared on Medscape.com.

Health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was confirmed in a 3-year-old girl in the capital, Lilongwe. It was the first case in Africa in 5 years, according to the World Health Organization.

Globally, there were only five cases of wild poliovirus in 2021, the WHO states.

“As long as wild polio exists anywhere in the world all countries remain at risk of importation of the virus,” Matshidiso Moeti, MBBS, WHO regional director for Africa, said in the statement.
 

Girl paralyzed in November

The Global Polio Eradication Initiative (GPEI) said in a statement that the 3-year-old girl  experienced paralysis in November, and stool specimens were collected. Sequencing of the virus was conducted in February, 2022, by the National Institute for Communicable Diseases in South Africa, and the Centers for Disease Control and Prevention confirmed the case as WPV1.

According to the WHO announcement, laboratory analysis shows that the strain identified in Malawi is linked to one circulating in Sindh Province in Pakistan. Polio remains endemic only in Afghanistan and Pakistan.

Kacey C. Ernst, PhD, MPH, professor and infectious disease epidemiologist at the University of Arizona’s Zuckerman College of Public Health in Tucson, pointed out that what is not clear from the press release is whether the girl had traveled to Pakistan or was infected in Malawi.

“This is a very significant detail that would indicate whether or not transmission was actively occurring in Malawi. Until that information is released, it is hard to judge the extent of the possible outbreak,” she said in an interview. “The good news is that this case was in fact detected. The surveillance systems are in place and they were able to identify wild-type cases.”

Dr. Ernst said that although there is cause for concern, it is “not a reason to panic. Malawi has very high polio vaccination rates and it is quite possible that this will be a very small defined outbreak that will be well contained.”

She added that the medical community should be alerted that this case has been identified so travelers who have been to affected areas who have any symptoms can be appropriately screened.

The WHO said it is helping Malawi health authorities in the response, including increasing immunizations.

However, a vaccination campaign comes at a time of health system upheaval in Malawi.

“Malawi, like countries all over the world, has seen an interruption in services due to COVID,” Joia S. Mukherjee, MD, MPH, chief medical officer with Partners in Health and associate professor with the division of global health equity at Brigham and Women’s Hospital and in the department of global health and social medicine at Harvard Medical School, Boston, said in an interview. “In addition, Malawi is currently dealing with the aftermath of a cyclone – where nearly a million people were displaced. Vaccination campaigns work best if there is solid infrastructure. Both COVID and the impact of climate change have shaken the health system.”

UN health agencies warned last year that millions of children who have not received immunizations during the pandemic, especially in Africa, “are now at risk from life-threatening diseases such as measles, polio, yellow fever, and diphtheria,” Reuters reported.

Africa was certified as wild poliovirus free on Aug. 25, 2020. The CDC had served as the lead partner over 3 decades in helping Africa reach the milestone. Africa will retain that status, the WHO stated, because the strain originated in Pakistan.

Five of six WHO regions have been certified polio free. The Americas received eradication certification in 1994.

There is no cure for polio, which can cause irreversible paralysis within hours, but the disease has been largely eradicated globally with an effective vaccine.
 

GPEI sending teams

The GPEI is sending a team to Malawi to support emergency operations, communications, and surveillance. Partner organizations will also send teams to support operations and innovative vaccination campaign solutions.

GPEI was launched in 1988 with the combined efforts of national governments, WHO, Rotary International, the CDC, and UNICEF. The GPEI partnership has included the Bill & Melinda Gates Foundation and, in recent years, Gavi, the Vaccine Alliance.

The CDC states, “[G]lobal incidence of polio has decreased by 99.9% since GPEI’s foundation. An estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive, whose lives would otherwise have been lost. Now the task remains to tackle polio in its last few strongholds and get rid of the final 0.1% of polio cases.”
 

Three wild poliovirus strains

There are three wild poliovirus strains: type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3).

“Symptomatically, all three strains are identical, in that they cause irreversible paralysis or even death. But there are genetic and virologic differences which make these three strains three separate viruses that must each be eradicated individually,” according to WHO.

WPV3 is the second strain to be wiped out, following the certification of the eradication of WPV2 in 2015.

A version of this article first appeared on Medscape.com.

Health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was confirmed in a 3-year-old girl in the capital, Lilongwe. It was the first case in Africa in 5 years, according to the World Health Organization.

Globally, there were only five cases of wild poliovirus in 2021, the WHO states.

“As long as wild polio exists anywhere in the world all countries remain at risk of importation of the virus,” Matshidiso Moeti, MBBS, WHO regional director for Africa, said in the statement.
 

Girl paralyzed in November

The Global Polio Eradication Initiative (GPEI) said in a statement that the 3-year-old girl  experienced paralysis in November, and stool specimens were collected. Sequencing of the virus was conducted in February, 2022, by the National Institute for Communicable Diseases in South Africa, and the Centers for Disease Control and Prevention confirmed the case as WPV1.

According to the WHO announcement, laboratory analysis shows that the strain identified in Malawi is linked to one circulating in Sindh Province in Pakistan. Polio remains endemic only in Afghanistan and Pakistan.

Kacey C. Ernst, PhD, MPH, professor and infectious disease epidemiologist at the University of Arizona’s Zuckerman College of Public Health in Tucson, pointed out that what is not clear from the press release is whether the girl had traveled to Pakistan or was infected in Malawi.

“This is a very significant detail that would indicate whether or not transmission was actively occurring in Malawi. Until that information is released, it is hard to judge the extent of the possible outbreak,” she said in an interview. “The good news is that this case was in fact detected. The surveillance systems are in place and they were able to identify wild-type cases.”

Dr. Ernst said that although there is cause for concern, it is “not a reason to panic. Malawi has very high polio vaccination rates and it is quite possible that this will be a very small defined outbreak that will be well contained.”

She added that the medical community should be alerted that this case has been identified so travelers who have been to affected areas who have any symptoms can be appropriately screened.

The WHO said it is helping Malawi health authorities in the response, including increasing immunizations.

However, a vaccination campaign comes at a time of health system upheaval in Malawi.

“Malawi, like countries all over the world, has seen an interruption in services due to COVID,” Joia S. Mukherjee, MD, MPH, chief medical officer with Partners in Health and associate professor with the division of global health equity at Brigham and Women’s Hospital and in the department of global health and social medicine at Harvard Medical School, Boston, said in an interview. “In addition, Malawi is currently dealing with the aftermath of a cyclone – where nearly a million people were displaced. Vaccination campaigns work best if there is solid infrastructure. Both COVID and the impact of climate change have shaken the health system.”

UN health agencies warned last year that millions of children who have not received immunizations during the pandemic, especially in Africa, “are now at risk from life-threatening diseases such as measles, polio, yellow fever, and diphtheria,” Reuters reported.

Africa was certified as wild poliovirus free on Aug. 25, 2020. The CDC had served as the lead partner over 3 decades in helping Africa reach the milestone. Africa will retain that status, the WHO stated, because the strain originated in Pakistan.

Five of six WHO regions have been certified polio free. The Americas received eradication certification in 1994.

There is no cure for polio, which can cause irreversible paralysis within hours, but the disease has been largely eradicated globally with an effective vaccine.
 

GPEI sending teams

The GPEI is sending a team to Malawi to support emergency operations, communications, and surveillance. Partner organizations will also send teams to support operations and innovative vaccination campaign solutions.

GPEI was launched in 1988 with the combined efforts of national governments, WHO, Rotary International, the CDC, and UNICEF. The GPEI partnership has included the Bill & Melinda Gates Foundation and, in recent years, Gavi, the Vaccine Alliance.

The CDC states, “[G]lobal incidence of polio has decreased by 99.9% since GPEI’s foundation. An estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive, whose lives would otherwise have been lost. Now the task remains to tackle polio in its last few strongholds and get rid of the final 0.1% of polio cases.”
 

Three wild poliovirus strains

There are three wild poliovirus strains: type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3).

“Symptomatically, all three strains are identical, in that they cause irreversible paralysis or even death. But there are genetic and virologic differences which make these three strains three separate viruses that must each be eradicated individually,” according to WHO.

WPV3 is the second strain to be wiped out, following the certification of the eradication of WPV2 in 2015.

A version of this article first appeared on Medscape.com.

In June 2017, Betty Balikagala, MD, PhD, traveled to a hospital in Gulu District, in northern Uganda. It was the rainy season: a peak time for malaria transmission. Dr. Balikagala, a researcher at Juntendo University in Japan, was back in her home country to hunt for mutations in the parasite that causes the disease.

For about 4 weeks, Dr. Balikagala and her colleagues collected blood from infected patients as they were treated with a powerful cocktail of antimalarial drugs. After initial analysis, the team then shipped their samples – glass slides smeared with blood, and filter papers with blood spots – back to Japan.

In their lab at Juntendo University, they looked for traces of malaria in the blood slides, which they had prepared by drawing blood from patients every few hours. In previous years, Dr. Balikagala and her colleagues had observed the drugs efficiently clearing the infection. This time, though, the parasite lingered in some patients. “We were very surprised when we first did the parasite reading for 2017, and we noticed that there were some patients who had delayed clearance,” recalled Dr. Balikagala. “For me, it was a shock.”

Malaria kills more than half a million people per year, most of them small children. Still, between 2000 and 2020, according to the World Health Organization, interventions prevented around 10.6 million malaria deaths, mostly in Africa. Bed nets and insecticides were responsible for most of the progress. But a fairly large number of lives were also saved by a new kind of antimalarial treatment: artemisinin-based combination therapies, or ACTs, that replaced older drugs such as chloroquine.

Used as a first-line treatment, ACTs have averted a significant number of malaria deaths since their introduction in the early 2000s. ACTs pair a derivative of the drug artemisinin with one of five partner drugs or drug combinations. Delivered together, the fast-acting artemisinin component wipes out most of the parasites within a few days, and the longer-acting partner drug clears out the stragglers.

ACTs quickly became a mainstay in malaria treatment. But in 2009, researchers observed signs of resistance to artemisinin along the Thailand-Cambodia border. The artemisinin component failed to clear the parasite quickly, which meant that the partner drug had to pick up that load, creating favorable conditions for partner drug resistance, too. The Greater Mekong Subregion now experiences high rates of multidrug resistance. Scientists have feared that the spread of such resistance to Africa, which accounts for more than 90% of global malaria cases, would be disastrous.

Now, in a pair of reports published last year, scientists have confirmed the emergence of artemisinin resistance in Africa. One study, published in April, reported that ACTs had failed to work quickly for more than 10% of participants at two sites in Rwanda. The prevalence of artemisinin resistance mutations was also higher than detected in previous reports.

In September, Dr. Balikagala’s team published the report from Uganda, which also identified mutations associated with artemisinin resistance. Alarmingly, the resistant malaria parasites had risen from 3.9% of cases in 2015 to nearly 20% in 2019. Genetic analysis shows that the resistance mutations in Rwanda and Uganda have emerged independently.

The latest malaria report from the WHO, published in December, also noted worrying signs of artemisinin resistance in the Horn of Africa, on the eastern side of the continent. No peer-reviewed studies confirming such resistance have been published.

So far, the ACTs still work. But in an experimental setting, as drug resistance sets in, it can lengthen treatment by 3 or 4 days. That may not sound like much, said Timothy Wells, PhD, chief scientific officer of the nonprofit Medicines for Malaria Venture. But “the more days of therapy you need,” he said, “then the more there is the risk that people don’t finish their course of therapy.” Dropping a treatment course midway exposes the parasites to the drug, but doesn’t clear all of them, potentially leaving behind survivors with a higher chance of being drug resistant. “That’s really bad news, because then that sets up a perfect storm for creating more resistance,” said Dr. Wells.

The reports from Uganda and Rwanda have yielded a grim consensus: “We are going to see more and more of such independent emergence,” said Pascal Ringwald, MD, PhD, coordinator at the director’s office for the WHO Global Malaria Program. “This is exactly what we saw in the Greater Mekong.” Luckily, Dr. Wells said, switching to other ACTs helped to combat resistance when it was detected there, avoiding the need for prolonged treatment.

A new malaria vaccine, which recently received the go-ahead from the WHO, may eventually help reduce the number of infections, but its rollout won’t have any significant impact on drug resistance. As for new drugs, even the most promising candidate in the pipeline would take at least 4 years to become widely available.

That leaves public health workers in Africa with only one solid option: Track and surveil resistance to artemisinin and its partner drugs. Effective surveillance systems, experts say, need to ramp up quickly and widely across the continent.

But most experts say that surveillance on the continent is patchy. Indeed, there is considerable uncertainty about how widespread antimalarial resistance already is in sub-Saharan Africa – and disagreement over how to interpret initial reports of emerging partner drug resistance in some countries.

“Our current systems are not as good as they should be,” said Philip Rosenthal, MD, a malaria researcher at the University of California, San Francisco. The new reports of artemisinin resistance, he added, “can be seen as a wake-up call to improve surveillance.”

Malaria drugs have failed before. In the early 20th century, chloroquine helped beat back the pathogen worldwide. Then, about a decade after World War II, resistance to chloroquine surfaced along the Thailand-Cambodia border.

By the 1970s, chloroquine-resistant malaria had spread across India and into Africa, where it killed millions, many of them children. “In retrospect, we know that chloroquine was used for many years after there was a huge resistance problem,” said Dr. Rosenthal. “This probably led to millions of excess deaths that could have been avoided if we were using other drugs.”

The scurry to find new drugs yielded artemisinin. Used by Chinese herbalists some 2,000 years ago to treat malaria-like symptoms, artemisinin was rediscovered in the 1970s by biomedical researchers in China, and its use became widespread in the 2000s.

Haunted by the failure of chloroquine, though, researchers have remained on the lookout for signs that the malaria parasite is evolving to resist artemisinin or its partner drugs. The gold-standard method is a therapeutic efficacy study, which involves closely monitoring infected patients as they are treated with antimalarial drugs, to see how well the drugs perform and if there are any signs of resistance.

The WHO recommends conducting these studies at several sites in a country every 2 years. But “each country interprets that with their capability,” said Philippe Guérin, MD, PhD, director of the WorldWide Antimalarial Resistance Network at the University of Oxford, England. Efficacy studies are slow, costly, and labor intensive. Also, “you don’t get a very good geographical representation,” said Dr. Guérin, because you can do a new clinical trial in only so many places at a time.

To get around the problems associated with efficacy studies, researchers also turn to molecular surveillance. Researchers draw a few drops of blood from an infected individual onto a filter paper, then scan it in the laboratory for certain genetic mutations associated with resistance. The technique is relatively easy and cheap.

With these kinds of surveillance data, policymakers can choose which drugs to use in a particular region. Moreover, early detection of resistance can prompt health authorities to take actions to limit the spread of resistance, including more aggressive screening and treatment campaigns, and expanded efforts to control the mosquitoes that spread malaria.

In practice, though, this warning system is frayed. “There is really no organized surveillance system for the continent,” said Dr. Rosenthal. “Surveillance is haphazard.”

In countries lacking a robust health care system or mired in political instability, experts say, resistance could be spreading undetected. For example, the border of South Sudan is just 60 miles from the site in northern Uganda where Dr. Balikagala and her colleagues confirmed resistance to artemisinin. “Because of the security issues and the refugee-weakened system, there is no surveillance that tells us what is happening in South Sudan,” said Dr. Guérin. The same applies in some parts of the nearby Democratic Republic of the Congo, he added.

In the past, regional antimalarial networks, such as the now defunct East African Network for Monitoring of Antimalarial Treatment, have addressed some surveillance gaps. These networks can help standardize protocols and coordinate surveillance efforts. But such networks have suffered from recent lapses in donor funding. The East African network “will be awakened,” Dr. Balikagala predicted, as concerns about artemisinin-resistant malaria grow.

In southern Africa, eight countries have come together to form the Elimination Eight Initiative, a coalition to facilitate malaria elimination efforts across national borders, which may help jump-start surveillance efforts there.

Dr. Ringwald said drug resistance is a priority for him and his WHO colleagues. At a malaria policy advisory committee meeting last fall, he said, the issue was “high on the agenda.” However, when pressed for answers on how the WHO plans to combat drug resistance in Africa, Dr. Ringwald emailed Undark an excerpt from the organization’s 2021 World Malaria Report. The report states that the WHO will “work with countries to develop a regional plan for a coordinated response,” but does not lay out any specifics on that response plan. The Africa Centers for Disease Control and Prevention, part of the African Union, did not respond to requests for comment on its plans to bolster surveillance.

“There is an ethical obligation to researchers, and to people responsible for surveillance, that if you pick up these problems, share them as quickly as possible, react to them as strongly as possible,” said Karen Barnes, a clinical pharmacologist at the University of Cape Town who cochairs the South African Malaria Elimination Committee. “And try very, very hard” to make sure “that it’s not going to be the same as when we had chloroquine resistance in Africa.”

In absence of more robust surveillance, reports have also identified worrying – but, some scientists say, inconclusive – signs of partner drug resistance.

A series of four studies conducted between 2013 and 2019 at several sites in Angola found the efficacy of artemether-lumefantrine – the most widely used ACT in Africa – had dropped below 90%, the WHO threshold for acceptable malaria treatment. Peer-reviewed studies from Burkina Faso and the Democratic Republic of the Congo have reported similar results.

The studies have not found genes associated with artemisinin resistance, suggesting that the partner drug, lumefantrine, might be faltering. But several malaria researchers told Undark they were skeptical of the studies’ methods and viewed the results as preliminary. “I would have preferred that we look at data with a standardized protocol and exclude any confounding factors like poor microscopy or analytical method,” said Dr. Ringwald.

Mateusz Plucinski, PhD, an epidemiologist at the Centers for Disease Control and Prevention’s Malaria Branch who participated in the Angola research, defended the findings. “The persistence of artemether-lumefantrine efficacy near or under 90% in Angola likely suggests that there is likely a true signal of decreased susceptibility of parasites to this drug,” he wrote in an email to this news organization. In response to the data, Angolan health officials have begun using a different ACT.

For now, it’s unclear how bad the situation is in Africa – or what the years ahead could bring. The research community and the authorities are “at the level of just watching and seeing what happens at this stage,” said Leann Tilley, PhD, a biochemist at the University of Melbourne who researches antimalarial resistance. But experts say that if artemisinin resistance does flare up and starts impinging on the partner drug, policymakers might need to consider changing to a different ACT, or even deploy triple ACTs, with two partner drugs.

Some experts are hopeful that artemisinin resistance will spread more slowly in Africa than it has in southeast Asia. But if high-grade resistance to artemisinin and partner drugs were to arise, it would put Africa in a bind. There are no immediate replacements for ACTs at the moment. The Medicines for Malaria Venture drug pipeline has about 30 molecules that show promise in preliminary testing, and about 15 molecules that are undergoing clinical trials for efficacy and safety, said Dr. Wells. But even the drugs that are at the end of the pipeline will take about 5-6 years from approval by regulatory authorities to be incorporated into WHO guidelines, he noted – if they make it through trials at all.

Dr. Wells cited one promising compound, from the drug maker Novartis, that recently performed well in early clinical trials. Still, Dr. Wells said, the drug won’t be ready to be deployed in Africa until around 2026.

Funds for malaria control and elimination programs remain limited, and scientists worry that, between COVID-19 and the malaria vaccine rollout, attention and resources for conducting surveillance and drug resistance work might dry up. “I really hope that those that do have resources available will understand that investing in Africa’s response to artemisinin resistance today, preferably yesterday, is probably one of the best places that they can put their money,” said Barnes.

The annals of malaria have shown time and again that once resistance emerges, it spreads widely and imperils progress against the deadly disease. For Africa, the writing is on the wall, she said. The bigger question, she asked, is this: “Are we capable of learning from history?”

A version of this article first appeared on Undark.com.

In June 2017, Betty Balikagala, MD, PhD, traveled to a hospital in Gulu District, in northern Uganda. It was the rainy season: a peak time for malaria transmission. Dr. Balikagala, a researcher at Juntendo University in Japan, was back in her home country to hunt for mutations in the parasite that causes the disease.

For about 4 weeks, Dr. Balikagala and her colleagues collected blood from infected patients as they were treated with a powerful cocktail of antimalarial drugs. After initial analysis, the team then shipped their samples – glass slides smeared with blood, and filter papers with blood spots – back to Japan.

In their lab at Juntendo University, they looked for traces of malaria in the blood slides, which they had prepared by drawing blood from patients every few hours. In previous years, Dr. Balikagala and her colleagues had observed the drugs efficiently clearing the infection. This time, though, the parasite lingered in some patients. “We were very surprised when we first did the parasite reading for 2017, and we noticed that there were some patients who had delayed clearance,” recalled Dr. Balikagala. “For me, it was a shock.”

Malaria kills more than half a million people per year, most of them small children. Still, between 2000 and 2020, according to the World Health Organization, interventions prevented around 10.6 million malaria deaths, mostly in Africa. Bed nets and insecticides were responsible for most of the progress. But a fairly large number of lives were also saved by a new kind of antimalarial treatment: artemisinin-based combination therapies, or ACTs, that replaced older drugs such as chloroquine.

Used as a first-line treatment, ACTs have averted a significant number of malaria deaths since their introduction in the early 2000s. ACTs pair a derivative of the drug artemisinin with one of five partner drugs or drug combinations. Delivered together, the fast-acting artemisinin component wipes out most of the parasites within a few days, and the longer-acting partner drug clears out the stragglers.

ACTs quickly became a mainstay in malaria treatment. But in 2009, researchers observed signs of resistance to artemisinin along the Thailand-Cambodia border. The artemisinin component failed to clear the parasite quickly, which meant that the partner drug had to pick up that load, creating favorable conditions for partner drug resistance, too. The Greater Mekong Subregion now experiences high rates of multidrug resistance. Scientists have feared that the spread of such resistance to Africa, which accounts for more than 90% of global malaria cases, would be disastrous.

Now, in a pair of reports published last year, scientists have confirmed the emergence of artemisinin resistance in Africa. One study, published in April, reported that ACTs had failed to work quickly for more than 10% of participants at two sites in Rwanda. The prevalence of artemisinin resistance mutations was also higher than detected in previous reports.

In September, Dr. Balikagala’s team published the report from Uganda, which also identified mutations associated with artemisinin resistance. Alarmingly, the resistant malaria parasites had risen from 3.9% of cases in 2015 to nearly 20% in 2019. Genetic analysis shows that the resistance mutations in Rwanda and Uganda have emerged independently.

The latest malaria report from the WHO, published in December, also noted worrying signs of artemisinin resistance in the Horn of Africa, on the eastern side of the continent. No peer-reviewed studies confirming such resistance have been published.

So far, the ACTs still work. But in an experimental setting, as drug resistance sets in, it can lengthen treatment by 3 or 4 days. That may not sound like much, said Timothy Wells, PhD, chief scientific officer of the nonprofit Medicines for Malaria Venture. But “the more days of therapy you need,” he said, “then the more there is the risk that people don’t finish their course of therapy.” Dropping a treatment course midway exposes the parasites to the drug, but doesn’t clear all of them, potentially leaving behind survivors with a higher chance of being drug resistant. “That’s really bad news, because then that sets up a perfect storm for creating more resistance,” said Dr. Wells.

The reports from Uganda and Rwanda have yielded a grim consensus: “We are going to see more and more of such independent emergence,” said Pascal Ringwald, MD, PhD, coordinator at the director’s office for the WHO Global Malaria Program. “This is exactly what we saw in the Greater Mekong.” Luckily, Dr. Wells said, switching to other ACTs helped to combat resistance when it was detected there, avoiding the need for prolonged treatment.

A new malaria vaccine, which recently received the go-ahead from the WHO, may eventually help reduce the number of infections, but its rollout won’t have any significant impact on drug resistance. As for new drugs, even the most promising candidate in the pipeline would take at least 4 years to become widely available.

That leaves public health workers in Africa with only one solid option: Track and surveil resistance to artemisinin and its partner drugs. Effective surveillance systems, experts say, need to ramp up quickly and widely across the continent.

But most experts say that surveillance on the continent is patchy. Indeed, there is considerable uncertainty about how widespread antimalarial resistance already is in sub-Saharan Africa – and disagreement over how to interpret initial reports of emerging partner drug resistance in some countries.

“Our current systems are not as good as they should be,” said Philip Rosenthal, MD, a malaria researcher at the University of California, San Francisco. The new reports of artemisinin resistance, he added, “can be seen as a wake-up call to improve surveillance.”

Malaria drugs have failed before. In the early 20th century, chloroquine helped beat back the pathogen worldwide. Then, about a decade after World War II, resistance to chloroquine surfaced along the Thailand-Cambodia border.

By the 1970s, chloroquine-resistant malaria had spread across India and into Africa, where it killed millions, many of them children. “In retrospect, we know that chloroquine was used for many years after there was a huge resistance problem,” said Dr. Rosenthal. “This probably led to millions of excess deaths that could have been avoided if we were using other drugs.”

The scurry to find new drugs yielded artemisinin. Used by Chinese herbalists some 2,000 years ago to treat malaria-like symptoms, artemisinin was rediscovered in the 1970s by biomedical researchers in China, and its use became widespread in the 2000s.

Haunted by the failure of chloroquine, though, researchers have remained on the lookout for signs that the malaria parasite is evolving to resist artemisinin or its partner drugs. The gold-standard method is a therapeutic efficacy study, which involves closely monitoring infected patients as they are treated with antimalarial drugs, to see how well the drugs perform and if there are any signs of resistance.

The WHO recommends conducting these studies at several sites in a country every 2 years. But “each country interprets that with their capability,” said Philippe Guérin, MD, PhD, director of the WorldWide Antimalarial Resistance Network at the University of Oxford, England. Efficacy studies are slow, costly, and labor intensive. Also, “you don’t get a very good geographical representation,” said Dr. Guérin, because you can do a new clinical trial in only so many places at a time.

To get around the problems associated with efficacy studies, researchers also turn to molecular surveillance. Researchers draw a few drops of blood from an infected individual onto a filter paper, then scan it in the laboratory for certain genetic mutations associated with resistance. The technique is relatively easy and cheap.

With these kinds of surveillance data, policymakers can choose which drugs to use in a particular region. Moreover, early detection of resistance can prompt health authorities to take actions to limit the spread of resistance, including more aggressive screening and treatment campaigns, and expanded efforts to control the mosquitoes that spread malaria.

In practice, though, this warning system is frayed. “There is really no organized surveillance system for the continent,” said Dr. Rosenthal. “Surveillance is haphazard.”

In countries lacking a robust health care system or mired in political instability, experts say, resistance could be spreading undetected. For example, the border of South Sudan is just 60 miles from the site in northern Uganda where Dr. Balikagala and her colleagues confirmed resistance to artemisinin. “Because of the security issues and the refugee-weakened system, there is no surveillance that tells us what is happening in South Sudan,” said Dr. Guérin. The same applies in some parts of the nearby Democratic Republic of the Congo, he added.

In the past, regional antimalarial networks, such as the now defunct East African Network for Monitoring of Antimalarial Treatment, have addressed some surveillance gaps. These networks can help standardize protocols and coordinate surveillance efforts. But such networks have suffered from recent lapses in donor funding. The East African network “will be awakened,” Dr. Balikagala predicted, as concerns about artemisinin-resistant malaria grow.

In southern Africa, eight countries have come together to form the Elimination Eight Initiative, a coalition to facilitate malaria elimination efforts across national borders, which may help jump-start surveillance efforts there.

Dr. Ringwald said drug resistance is a priority for him and his WHO colleagues. At a malaria policy advisory committee meeting last fall, he said, the issue was “high on the agenda.” However, when pressed for answers on how the WHO plans to combat drug resistance in Africa, Dr. Ringwald emailed Undark an excerpt from the organization’s 2021 World Malaria Report. The report states that the WHO will “work with countries to develop a regional plan for a coordinated response,” but does not lay out any specifics on that response plan. The Africa Centers for Disease Control and Prevention, part of the African Union, did not respond to requests for comment on its plans to bolster surveillance.

“There is an ethical obligation to researchers, and to people responsible for surveillance, that if you pick up these problems, share them as quickly as possible, react to them as strongly as possible,” said Karen Barnes, a clinical pharmacologist at the University of Cape Town who cochairs the South African Malaria Elimination Committee. “And try very, very hard” to make sure “that it’s not going to be the same as when we had chloroquine resistance in Africa.”

In absence of more robust surveillance, reports have also identified worrying – but, some scientists say, inconclusive – signs of partner drug resistance.

A series of four studies conducted between 2013 and 2019 at several sites in Angola found the efficacy of artemether-lumefantrine – the most widely used ACT in Africa – had dropped below 90%, the WHO threshold for acceptable malaria treatment. Peer-reviewed studies from Burkina Faso and the Democratic Republic of the Congo have reported similar results.

The studies have not found genes associated with artemisinin resistance, suggesting that the partner drug, lumefantrine, might be faltering. But several malaria researchers told Undark they were skeptical of the studies’ methods and viewed the results as preliminary. “I would have preferred that we look at data with a standardized protocol and exclude any confounding factors like poor microscopy or analytical method,” said Dr. Ringwald.

Mateusz Plucinski, PhD, an epidemiologist at the Centers for Disease Control and Prevention’s Malaria Branch who participated in the Angola research, defended the findings. “The persistence of artemether-lumefantrine efficacy near or under 90% in Angola likely suggests that there is likely a true signal of decreased susceptibility of parasites to this drug,” he wrote in an email to this news organization. In response to the data, Angolan health officials have begun using a different ACT.

For now, it’s unclear how bad the situation is in Africa – or what the years ahead could bring. The research community and the authorities are “at the level of just watching and seeing what happens at this stage,” said Leann Tilley, PhD, a biochemist at the University of Melbourne who researches antimalarial resistance. But experts say that if artemisinin resistance does flare up and starts impinging on the partner drug, policymakers might need to consider changing to a different ACT, or even deploy triple ACTs, with two partner drugs.

Some experts are hopeful that artemisinin resistance will spread more slowly in Africa than it has in southeast Asia. But if high-grade resistance to artemisinin and partner drugs were to arise, it would put Africa in a bind. There are no immediate replacements for ACTs at the moment. The Medicines for Malaria Venture drug pipeline has about 30 molecules that show promise in preliminary testing, and about 15 molecules that are undergoing clinical trials for efficacy and safety, said Dr. Wells. But even the drugs that are at the end of the pipeline will take about 5-6 years from approval by regulatory authorities to be incorporated into WHO guidelines, he noted – if they make it through trials at all.

Dr. Wells cited one promising compound, from the drug maker Novartis, that recently performed well in early clinical trials. Still, Dr. Wells said, the drug won’t be ready to be deployed in Africa until around 2026.

Funds for malaria control and elimination programs remain limited, and scientists worry that, between COVID-19 and the malaria vaccine rollout, attention and resources for conducting surveillance and drug resistance work might dry up. “I really hope that those that do have resources available will understand that investing in Africa’s response to artemisinin resistance today, preferably yesterday, is probably one of the best places that they can put their money,” said Barnes.

The annals of malaria have shown time and again that once resistance emerges, it spreads widely and imperils progress against the deadly disease. For Africa, the writing is on the wall, she said. The bigger question, she asked, is this: “Are we capable of learning from history?”

A version of this article first appeared on Undark.com.

In June 2017, Betty Balikagala, MD, PhD, traveled to a hospital in Gulu District, in northern Uganda. It was the rainy season: a peak time for malaria transmission. Dr. Balikagala, a researcher at Juntendo University in Japan, was back in her home country to hunt for mutations in the parasite that causes the disease.

For about 4 weeks, Dr. Balikagala and her colleagues collected blood from infected patients as they were treated with a powerful cocktail of antimalarial drugs. After initial analysis, the team then shipped their samples – glass slides smeared with blood, and filter papers with blood spots – back to Japan.

In their lab at Juntendo University, they looked for traces of malaria in the blood slides, which they had prepared by drawing blood from patients every few hours. In previous years, Dr. Balikagala and her colleagues had observed the drugs efficiently clearing the infection. This time, though, the parasite lingered in some patients. “We were very surprised when we first did the parasite reading for 2017, and we noticed that there were some patients who had delayed clearance,” recalled Dr. Balikagala. “For me, it was a shock.”

Malaria kills more than half a million people per year, most of them small children. Still, between 2000 and 2020, according to the World Health Organization, interventions prevented around 10.6 million malaria deaths, mostly in Africa. Bed nets and insecticides were responsible for most of the progress. But a fairly large number of lives were also saved by a new kind of antimalarial treatment: artemisinin-based combination therapies, or ACTs, that replaced older drugs such as chloroquine.

Used as a first-line treatment, ACTs have averted a significant number of malaria deaths since their introduction in the early 2000s. ACTs pair a derivative of the drug artemisinin with one of five partner drugs or drug combinations. Delivered together, the fast-acting artemisinin component wipes out most of the parasites within a few days, and the longer-acting partner drug clears out the stragglers.

ACTs quickly became a mainstay in malaria treatment. But in 2009, researchers observed signs of resistance to artemisinin along the Thailand-Cambodia border. The artemisinin component failed to clear the parasite quickly, which meant that the partner drug had to pick up that load, creating favorable conditions for partner drug resistance, too. The Greater Mekong Subregion now experiences high rates of multidrug resistance. Scientists have feared that the spread of such resistance to Africa, which accounts for more than 90% of global malaria cases, would be disastrous.

Now, in a pair of reports published last year, scientists have confirmed the emergence of artemisinin resistance in Africa. One study, published in April, reported that ACTs had failed to work quickly for more than 10% of participants at two sites in Rwanda. The prevalence of artemisinin resistance mutations was also higher than detected in previous reports.

In September, Dr. Balikagala’s team published the report from Uganda, which also identified mutations associated with artemisinin resistance. Alarmingly, the resistant malaria parasites had risen from 3.9% of cases in 2015 to nearly 20% in 2019. Genetic analysis shows that the resistance mutations in Rwanda and Uganda have emerged independently.

The latest malaria report from the WHO, published in December, also noted worrying signs of artemisinin resistance in the Horn of Africa, on the eastern side of the continent. No peer-reviewed studies confirming such resistance have been published.

So far, the ACTs still work. But in an experimental setting, as drug resistance sets in, it can lengthen treatment by 3 or 4 days. That may not sound like much, said Timothy Wells, PhD, chief scientific officer of the nonprofit Medicines for Malaria Venture. But “the more days of therapy you need,” he said, “then the more there is the risk that people don’t finish their course of therapy.” Dropping a treatment course midway exposes the parasites to the drug, but doesn’t clear all of them, potentially leaving behind survivors with a higher chance of being drug resistant. “That’s really bad news, because then that sets up a perfect storm for creating more resistance,” said Dr. Wells.

The reports from Uganda and Rwanda have yielded a grim consensus: “We are going to see more and more of such independent emergence,” said Pascal Ringwald, MD, PhD, coordinator at the director’s office for the WHO Global Malaria Program. “This is exactly what we saw in the Greater Mekong.” Luckily, Dr. Wells said, switching to other ACTs helped to combat resistance when it was detected there, avoiding the need for prolonged treatment.

A new malaria vaccine, which recently received the go-ahead from the WHO, may eventually help reduce the number of infections, but its rollout won’t have any significant impact on drug resistance. As for new drugs, even the most promising candidate in the pipeline would take at least 4 years to become widely available.

That leaves public health workers in Africa with only one solid option: Track and surveil resistance to artemisinin and its partner drugs. Effective surveillance systems, experts say, need to ramp up quickly and widely across the continent.

But most experts say that surveillance on the continent is patchy. Indeed, there is considerable uncertainty about how widespread antimalarial resistance already is in sub-Saharan Africa – and disagreement over how to interpret initial reports of emerging partner drug resistance in some countries.

“Our current systems are not as good as they should be,” said Philip Rosenthal, MD, a malaria researcher at the University of California, San Francisco. The new reports of artemisinin resistance, he added, “can be seen as a wake-up call to improve surveillance.”

Malaria drugs have failed before. In the early 20th century, chloroquine helped beat back the pathogen worldwide. Then, about a decade after World War II, resistance to chloroquine surfaced along the Thailand-Cambodia border.

By the 1970s, chloroquine-resistant malaria had spread across India and into Africa, where it killed millions, many of them children. “In retrospect, we know that chloroquine was used for many years after there was a huge resistance problem,” said Dr. Rosenthal. “This probably led to millions of excess deaths that could have been avoided if we were using other drugs.”

The scurry to find new drugs yielded artemisinin. Used by Chinese herbalists some 2,000 years ago to treat malaria-like symptoms, artemisinin was rediscovered in the 1970s by biomedical researchers in China, and its use became widespread in the 2000s.

Haunted by the failure of chloroquine, though, researchers have remained on the lookout for signs that the malaria parasite is evolving to resist artemisinin or its partner drugs. The gold-standard method is a therapeutic efficacy study, which involves closely monitoring infected patients as they are treated with antimalarial drugs, to see how well the drugs perform and if there are any signs of resistance.

The WHO recommends conducting these studies at several sites in a country every 2 years. But “each country interprets that with their capability,” said Philippe Guérin, MD, PhD, director of the WorldWide Antimalarial Resistance Network at the University of Oxford, England. Efficacy studies are slow, costly, and labor intensive. Also, “you don’t get a very good geographical representation,” said Dr. Guérin, because you can do a new clinical trial in only so many places at a time.

To get around the problems associated with efficacy studies, researchers also turn to molecular surveillance. Researchers draw a few drops of blood from an infected individual onto a filter paper, then scan it in the laboratory for certain genetic mutations associated with resistance. The technique is relatively easy and cheap.

With these kinds of surveillance data, policymakers can choose which drugs to use in a particular region. Moreover, early detection of resistance can prompt health authorities to take actions to limit the spread of resistance, including more aggressive screening and treatment campaigns, and expanded efforts to control the mosquitoes that spread malaria.

In practice, though, this warning system is frayed. “There is really no organized surveillance system for the continent,” said Dr. Rosenthal. “Surveillance is haphazard.”

In countries lacking a robust health care system or mired in political instability, experts say, resistance could be spreading undetected. For example, the border of South Sudan is just 60 miles from the site in northern Uganda where Dr. Balikagala and her colleagues confirmed resistance to artemisinin. “Because of the security issues and the refugee-weakened system, there is no surveillance that tells us what is happening in South Sudan,” said Dr. Guérin. The same applies in some parts of the nearby Democratic Republic of the Congo, he added.

In the past, regional antimalarial networks, such as the now defunct East African Network for Monitoring of Antimalarial Treatment, have addressed some surveillance gaps. These networks can help standardize protocols and coordinate surveillance efforts. But such networks have suffered from recent lapses in donor funding. The East African network “will be awakened,” Dr. Balikagala predicted, as concerns about artemisinin-resistant malaria grow.

In southern Africa, eight countries have come together to form the Elimination Eight Initiative, a coalition to facilitate malaria elimination efforts across national borders, which may help jump-start surveillance efforts there.

Dr. Ringwald said drug resistance is a priority for him and his WHO colleagues. At a malaria policy advisory committee meeting last fall, he said, the issue was “high on the agenda.” However, when pressed for answers on how the WHO plans to combat drug resistance in Africa, Dr. Ringwald emailed Undark an excerpt from the organization’s 2021 World Malaria Report. The report states that the WHO will “work with countries to develop a regional plan for a coordinated response,” but does not lay out any specifics on that response plan. The Africa Centers for Disease Control and Prevention, part of the African Union, did not respond to requests for comment on its plans to bolster surveillance.

“There is an ethical obligation to researchers, and to people responsible for surveillance, that if you pick up these problems, share them as quickly as possible, react to them as strongly as possible,” said Karen Barnes, a clinical pharmacologist at the University of Cape Town who cochairs the South African Malaria Elimination Committee. “And try very, very hard” to make sure “that it’s not going to be the same as when we had chloroquine resistance in Africa.”

In absence of more robust surveillance, reports have also identified worrying – but, some scientists say, inconclusive – signs of partner drug resistance.

A series of four studies conducted between 2013 and 2019 at several sites in Angola found the efficacy of artemether-lumefantrine – the most widely used ACT in Africa – had dropped below 90%, the WHO threshold for acceptable malaria treatment. Peer-reviewed studies from Burkina Faso and the Democratic Republic of the Congo have reported similar results.

The studies have not found genes associated with artemisinin resistance, suggesting that the partner drug, lumefantrine, might be faltering. But several malaria researchers told Undark they were skeptical of the studies’ methods and viewed the results as preliminary. “I would have preferred that we look at data with a standardized protocol and exclude any confounding factors like poor microscopy or analytical method,” said Dr. Ringwald.

Mateusz Plucinski, PhD, an epidemiologist at the Centers for Disease Control and Prevention’s Malaria Branch who participated in the Angola research, defended the findings. “The persistence of artemether-lumefantrine efficacy near or under 90% in Angola likely suggests that there is likely a true signal of decreased susceptibility of parasites to this drug,” he wrote in an email to this news organization. In response to the data, Angolan health officials have begun using a different ACT.

For now, it’s unclear how bad the situation is in Africa – or what the years ahead could bring. The research community and the authorities are “at the level of just watching and seeing what happens at this stage,” said Leann Tilley, PhD, a biochemist at the University of Melbourne who researches antimalarial resistance. But experts say that if artemisinin resistance does flare up and starts impinging on the partner drug, policymakers might need to consider changing to a different ACT, or even deploy triple ACTs, with two partner drugs.

Some experts are hopeful that artemisinin resistance will spread more slowly in Africa than it has in southeast Asia. But if high-grade resistance to artemisinin and partner drugs were to arise, it would put Africa in a bind. There are no immediate replacements for ACTs at the moment. The Medicines for Malaria Venture drug pipeline has about 30 molecules that show promise in preliminary testing, and about 15 molecules that are undergoing clinical trials for efficacy and safety, said Dr. Wells. But even the drugs that are at the end of the pipeline will take about 5-6 years from approval by regulatory authorities to be incorporated into WHO guidelines, he noted – if they make it through trials at all.

Dr. Wells cited one promising compound, from the drug maker Novartis, that recently performed well in early clinical trials. Still, Dr. Wells said, the drug won’t be ready to be deployed in Africa until around 2026.

Funds for malaria control and elimination programs remain limited, and scientists worry that, between COVID-19 and the malaria vaccine rollout, attention and resources for conducting surveillance and drug resistance work might dry up. “I really hope that those that do have resources available will understand that investing in Africa’s response to artemisinin resistance today, preferably yesterday, is probably one of the best places that they can put their money,” said Barnes.

The annals of malaria have shown time and again that once resistance emerges, it spreads widely and imperils progress against the deadly disease. For Africa, the writing is on the wall, she said. The bigger question, she asked, is this: “Are we capable of learning from history?”

A version of this article first appeared on Undark.com.

The Centers for Disease Control and Prevention is setting up a new hub to watch for early warning signs of future infectious outbreaks, the agency announced on Aug. 18.

Epidemiologists learn about emerging outbreaks by tracking information, and the quality of their analysis depends on their access to high-quality data. Gaps in existing systems became obvious during the COVID-19 pandemic as experts were challenged by the crisis.

The new Center for Forecasting and Outbreak Analytics will, in part, work like a meteorological office that tracks weather-related changes, only the center will track possible flareups in infectious disease.

The day after he took office, President Joe Biden pledged to modernize the country’s system for public health data. First funding for the initiative will come from the American Rescue Plan.

“We are excited to have the expertise and ability to model and forecast public health concerns and share information in real-time to activate governmental, private sector, and public actions in anticipation of threats both domestically and abroad,” CDC Director Rochelle Walensky, MD, said in a statement.
 

Devastating toll of COVID-19

Many world leaders are now responding to the destruction of the health crisis and are investing in new infrastructure. A July report from a G-20 panel calls for $75 billion in international financing for pandemic prevention and preparedness –twice as much as current spending levels.

Testifying in a congressional hearing, epidemiologist Caitlin Rivers, PhD, from the Johns Hopkins Center for Health Security, Baltimore, voiced the importance of never being caught unprepared again.

“We were unprepared to manage the emergence and swift global spread of the novel coronavirus, and we were late to recognize when it reached our shores. Those delays set us on a worse trajectory than we might have otherwise faced,” she said.

Dr. Rivers will join the new center’s leadership team as associate director working alongside Marc Lipsitch, PhD, director for science.

“The new center will meet a longstanding need for a national focal point to analyze data and forecast the trajectory of pandemics with the express goal of informing and improving decisions with the best available evidence,” Dr. Lipsitch said in the CDC’s news release announcing the new center.

Experts will map what data sources are needed to assist disease modelers and public health emergency responders tracking emerging problems that they can share with decision-makers. They will expand tracking capability and data sharing using open-source software and application programming with existing and new data streams from the public health ecosystem and elsewhere.

Dylan George, PhD, who will be the center’s director for operations, said in the CDC news release that the center will provide critical information to communities so they can respond.

“Pandemics threaten our families and communities at speed and scale – our response needs to move at speed and scale, too,” he said.

A version of this article first appeared on WebMD.com.

The Centers for Disease Control and Prevention is setting up a new hub to watch for early warning signs of future infectious outbreaks, the agency announced on Aug. 18.

Epidemiologists learn about emerging outbreaks by tracking information, and the quality of their analysis depends on their access to high-quality data. Gaps in existing systems became obvious during the COVID-19 pandemic as experts were challenged by the crisis.

The new Center for Forecasting and Outbreak Analytics will, in part, work like a meteorological office that tracks weather-related changes, only the center will track possible flareups in infectious disease.

The day after he took office, President Joe Biden pledged to modernize the country’s system for public health data. First funding for the initiative will come from the American Rescue Plan.

“We are excited to have the expertise and ability to model and forecast public health concerns and share information in real-time to activate governmental, private sector, and public actions in anticipation of threats both domestically and abroad,” CDC Director Rochelle Walensky, MD, said in a statement.
 

Devastating toll of COVID-19

Many world leaders are now responding to the destruction of the health crisis and are investing in new infrastructure. A July report from a G-20 panel calls for $75 billion in international financing for pandemic prevention and preparedness –twice as much as current spending levels.

Testifying in a congressional hearing, epidemiologist Caitlin Rivers, PhD, from the Johns Hopkins Center for Health Security, Baltimore, voiced the importance of never being caught unprepared again.

“We were unprepared to manage the emergence and swift global spread of the novel coronavirus, and we were late to recognize when it reached our shores. Those delays set us on a worse trajectory than we might have otherwise faced,” she said.

Dr. Rivers will join the new center’s leadership team as associate director working alongside Marc Lipsitch, PhD, director for science.

“The new center will meet a longstanding need for a national focal point to analyze data and forecast the trajectory of pandemics with the express goal of informing and improving decisions with the best available evidence,” Dr. Lipsitch said in the CDC’s news release announcing the new center.

Experts will map what data sources are needed to assist disease modelers and public health emergency responders tracking emerging problems that they can share with decision-makers. They will expand tracking capability and data sharing using open-source software and application programming with existing and new data streams from the public health ecosystem and elsewhere.

Dylan George, PhD, who will be the center’s director for operations, said in the CDC news release that the center will provide critical information to communities so they can respond.

“Pandemics threaten our families and communities at speed and scale – our response needs to move at speed and scale, too,” he said.

A version of this article first appeared on WebMD.com.

The Centers for Disease Control and Prevention is setting up a new hub to watch for early warning signs of future infectious outbreaks, the agency announced on Aug. 18.

Epidemiologists learn about emerging outbreaks by tracking information, and the quality of their analysis depends on their access to high-quality data. Gaps in existing systems became obvious during the COVID-19 pandemic as experts were challenged by the crisis.

The new Center for Forecasting and Outbreak Analytics will, in part, work like a meteorological office that tracks weather-related changes, only the center will track possible flareups in infectious disease.

The day after he took office, President Joe Biden pledged to modernize the country’s system for public health data. First funding for the initiative will come from the American Rescue Plan.

“We are excited to have the expertise and ability to model and forecast public health concerns and share information in real-time to activate governmental, private sector, and public actions in anticipation of threats both domestically and abroad,” CDC Director Rochelle Walensky, MD, said in a statement.
 

Devastating toll of COVID-19

Many world leaders are now responding to the destruction of the health crisis and are investing in new infrastructure. A July report from a G-20 panel calls for $75 billion in international financing for pandemic prevention and preparedness –twice as much as current spending levels.

Testifying in a congressional hearing, epidemiologist Caitlin Rivers, PhD, from the Johns Hopkins Center for Health Security, Baltimore, voiced the importance of never being caught unprepared again.

“We were unprepared to manage the emergence and swift global spread of the novel coronavirus, and we were late to recognize when it reached our shores. Those delays set us on a worse trajectory than we might have otherwise faced,” she said.

Dr. Rivers will join the new center’s leadership team as associate director working alongside Marc Lipsitch, PhD, director for science.

“The new center will meet a longstanding need for a national focal point to analyze data and forecast the trajectory of pandemics with the express goal of informing and improving decisions with the best available evidence,” Dr. Lipsitch said in the CDC’s news release announcing the new center.

Experts will map what data sources are needed to assist disease modelers and public health emergency responders tracking emerging problems that they can share with decision-makers. They will expand tracking capability and data sharing using open-source software and application programming with existing and new data streams from the public health ecosystem and elsewhere.

Dylan George, PhD, who will be the center’s director for operations, said in the CDC news release that the center will provide critical information to communities so they can respond.

“Pandemics threaten our families and communities at speed and scale – our response needs to move at speed and scale, too,” he said.

A version of this article first appeared on WebMD.com.

The Centers for Disease Control has issued the first recommendations for the prevention and treatment of plague since 2000. The new guidelines focus on the possibility of bioterrorism with mass casualty events from an intentional release of Yersinia pestis.

Plague, a deadly infection caused by Y. pestis, has been feared throughout history because of large pandemics. The most well-known pandemic was the so-called Black Death in the fourteenth century, during which more than 50 million Europeans died. The biggest concern now is the spread of the bacteria by bioterrorism.

The CDC based their revised guidelines on an extensive systematic review of the literature and multiple sessions with about 90 experts in infectious disease, public health, emergency medicine, obgyn, maternal-fetal health, and pediatrics, in addition to representatives from a wide range of federal agencies.
 

Key changes

Christina Nelson, a medical officer with the CDC’s Division of Vector-Borne Diseases, told this news organization that now “we have been fortunate to have extended options for treatment.” Previously, “streptomycin and gentamicin were the first-line options for adults,” she said. Now, on the basis of additional evidence, “[we’re] able to … elevate the fluoroquinolones to first-line treatments.”

On the basis of the Animal Rule, which allows approval of antibiotics without human testing if such testing is not possible, the U.S. Food and Drug Administration has approved several quinolones for both treatment and prophylaxis of plague.

The guidelines offer same-class alternative antibiotics to meet surge capacity. Similarly, trimethoprim-sulfamethoxazole is now an alternative for prophylaxis.

There are additional oral options to conserve IV medications and supplies in a mass casualty event.

For the first time, the CDC added specific recommendations for pregnant women. Gigi Kwik Gronvall, PhD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, told this news organization that she was pleased to see this addition, because “effects on women and during pregnancy are not fully addressed, and it leads to problems down the road, like with COVID, [for which] they didn’t include pregnant people in their clinical trials for the vaccines [and] don’t have enough data to convince pregnant women to actually get the vaccine.”
 

Bubonic plague

Plague occurs globally, with natural sylvatic (wild animal) outbreaks occurring among rodents and small mammals. It is spread by fleas. When an infected flea bites a human, the person can become infected, most commonly as “bubonic” plague, with swollen lymph nodes, called buboes. Transmission can also occur between people by contact with infected fluids or inhalation of infectious droplets.

Gentamicin or streptomycin remain first-line agents for treating bubonic plague. When used as monotherapy, the survival rate is 91%. They have to be given parenterally and are associated with both nephroroxicity and ototoxicity; patients require monitoring.

Alternative first-line drugs now include high-dose ciprofloxicin, levofloxacin, moxifloxacin, and doxycycline. Each is administered either intravenously or orally.

Physicians should consider dual therapy and drainage for patients with large buboes. Treatment is for 10 to 14 days.
 

Pneumonic and septicemic plague

The pneumonic and septicemic forms of infection are deadlier than the bubonic. Pneumonic plague can be acquired from inhalation of infected bacteria from animals or people, from lab accidents, or from intentional aerosolization. Without treatment, these forms are almost always fatal. With treatment with aminoglycosides, fluoroquinolones, or tetracyclines, alone or in combination, survival is 82% to 83%. With naturally occurring pneumonic plague, the CDC now recommends levofloxacin or moxifloxacin to cover for community-acquired pneumonia if the source of the infection is uncertain.

Because plague is life threatening, doxycycline is not considered contraindicated in children. It has not been shown to cause tooth staining, unlike other tetracyclines, which should still be avoided if possible.
 

Meningitis

About 10% of people infected with bubonic plague develop plague meningitis. Symptoms are stiff neck, fever, headache, and coma. The current recommendation for treating plague meningitis is chloramphenicol and moxifloxacin or levofloxacin. However, quinolones can cause seizures, and clinicians should take that into account.

Infection control

Plague is transmitted between people by droplets, so caretakers should wear a mask in addition to taking standard precautions. They should add eye protection and a face shield if splashing is likely. Airborne precautions are not needed. Plague is not very transmissible from person to person; each infected person on average infects only 1.18 other people. In comparison, someone with chicken pox infects 9 to 10 people on average.

Bioterrorism

A deliberate attack would likely go undetected until a cluster or unusual pattern of disease became evident. With Y. pestis, the infectious dose is low. According to the guidelines, modeling suggests that a “release of 50 kg of Y. pestis into the air over a city of 5 million persons could result in 150,000 cases of pneumonic plague and 36,000 deaths.”

Because the former Union of the Soviet Socialist Republics (USSR) engineered antibiotic-resistant Y. pestis, antibiotics from two different classes should be used empirically until sensitivity tests become available.

Antibiotic prophylaxis would also have to be considered for exposed individuals. Recommendations would be developed at the time by federal and state experts, based in part on the magnitude of the event and the availability of masks and different classes of antibiotics.

Dr. Gronvall stressed the need for awareness, saying, “It’s important for people to remember that the first sign of the potential attack could be somebody coming into your hospital.”

Dr. Nelson added, “One of the main take-home messages ... is that plague still happens, it still happens in the western United States, it still happens around the world ... It’s not just a relic of history.” She emphasized that clinicians need to be thinking about it, because “it’s very important to get antibiotics on board early ... Then patients generally have a good prognosis.”

Dr. Nelson and Dr. Gronvall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Centers for Disease Control has issued the first recommendations for the prevention and treatment of plague since 2000. The new guidelines focus on the possibility of bioterrorism with mass casualty events from an intentional release of Yersinia pestis.

Plague, a deadly infection caused by Y. pestis, has been feared throughout history because of large pandemics. The most well-known pandemic was the so-called Black Death in the fourteenth century, during which more than 50 million Europeans died. The biggest concern now is the spread of the bacteria by bioterrorism.

The CDC based their revised guidelines on an extensive systematic review of the literature and multiple sessions with about 90 experts in infectious disease, public health, emergency medicine, obgyn, maternal-fetal health, and pediatrics, in addition to representatives from a wide range of federal agencies.
 

Key changes

Christina Nelson, a medical officer with the CDC’s Division of Vector-Borne Diseases, told this news organization that now “we have been fortunate to have extended options for treatment.” Previously, “streptomycin and gentamicin were the first-line options for adults,” she said. Now, on the basis of additional evidence, “[we’re] able to … elevate the fluoroquinolones to first-line treatments.”

On the basis of the Animal Rule, which allows approval of antibiotics without human testing if such testing is not possible, the U.S. Food and Drug Administration has approved several quinolones for both treatment and prophylaxis of plague.

The guidelines offer same-class alternative antibiotics to meet surge capacity. Similarly, trimethoprim-sulfamethoxazole is now an alternative for prophylaxis.

There are additional oral options to conserve IV medications and supplies in a mass casualty event.

For the first time, the CDC added specific recommendations for pregnant women. Gigi Kwik Gronvall, PhD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, told this news organization that she was pleased to see this addition, because “effects on women and during pregnancy are not fully addressed, and it leads to problems down the road, like with COVID, [for which] they didn’t include pregnant people in their clinical trials for the vaccines [and] don’t have enough data to convince pregnant women to actually get the vaccine.”
 

Bubonic plague

Plague occurs globally, with natural sylvatic (wild animal) outbreaks occurring among rodents and small mammals. It is spread by fleas. When an infected flea bites a human, the person can become infected, most commonly as “bubonic” plague, with swollen lymph nodes, called buboes. Transmission can also occur between people by contact with infected fluids or inhalation of infectious droplets.

Gentamicin or streptomycin remain first-line agents for treating bubonic plague. When used as monotherapy, the survival rate is 91%. They have to be given parenterally and are associated with both nephroroxicity and ototoxicity; patients require monitoring.

Alternative first-line drugs now include high-dose ciprofloxicin, levofloxacin, moxifloxacin, and doxycycline. Each is administered either intravenously or orally.

Physicians should consider dual therapy and drainage for patients with large buboes. Treatment is for 10 to 14 days.
 

Pneumonic and septicemic plague

The pneumonic and septicemic forms of infection are deadlier than the bubonic. Pneumonic plague can be acquired from inhalation of infected bacteria from animals or people, from lab accidents, or from intentional aerosolization. Without treatment, these forms are almost always fatal. With treatment with aminoglycosides, fluoroquinolones, or tetracyclines, alone or in combination, survival is 82% to 83%. With naturally occurring pneumonic plague, the CDC now recommends levofloxacin or moxifloxacin to cover for community-acquired pneumonia if the source of the infection is uncertain.

Because plague is life threatening, doxycycline is not considered contraindicated in children. It has not been shown to cause tooth staining, unlike other tetracyclines, which should still be avoided if possible.
 

Meningitis

About 10% of people infected with bubonic plague develop plague meningitis. Symptoms are stiff neck, fever, headache, and coma. The current recommendation for treating plague meningitis is chloramphenicol and moxifloxacin or levofloxacin. However, quinolones can cause seizures, and clinicians should take that into account.

Infection control

Plague is transmitted between people by droplets, so caretakers should wear a mask in addition to taking standard precautions. They should add eye protection and a face shield if splashing is likely. Airborne precautions are not needed. Plague is not very transmissible from person to person; each infected person on average infects only 1.18 other people. In comparison, someone with chicken pox infects 9 to 10 people on average.

Bioterrorism

A deliberate attack would likely go undetected until a cluster or unusual pattern of disease became evident. With Y. pestis, the infectious dose is low. According to the guidelines, modeling suggests that a “release of 50 kg of Y. pestis into the air over a city of 5 million persons could result in 150,000 cases of pneumonic plague and 36,000 deaths.”

Because the former Union of the Soviet Socialist Republics (USSR) engineered antibiotic-resistant Y. pestis, antibiotics from two different classes should be used empirically until sensitivity tests become available.

Antibiotic prophylaxis would also have to be considered for exposed individuals. Recommendations would be developed at the time by federal and state experts, based in part on the magnitude of the event and the availability of masks and different classes of antibiotics.

Dr. Gronvall stressed the need for awareness, saying, “It’s important for people to remember that the first sign of the potential attack could be somebody coming into your hospital.”

Dr. Nelson added, “One of the main take-home messages ... is that plague still happens, it still happens in the western United States, it still happens around the world ... It’s not just a relic of history.” She emphasized that clinicians need to be thinking about it, because “it’s very important to get antibiotics on board early ... Then patients generally have a good prognosis.”

Dr. Nelson and Dr. Gronvall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Centers for Disease Control has issued the first recommendations for the prevention and treatment of plague since 2000. The new guidelines focus on the possibility of bioterrorism with mass casualty events from an intentional release of Yersinia pestis.

Plague, a deadly infection caused by Y. pestis, has been feared throughout history because of large pandemics. The most well-known pandemic was the so-called Black Death in the fourteenth century, during which more than 50 million Europeans died. The biggest concern now is the spread of the bacteria by bioterrorism.

The CDC based their revised guidelines on an extensive systematic review of the literature and multiple sessions with about 90 experts in infectious disease, public health, emergency medicine, obgyn, maternal-fetal health, and pediatrics, in addition to representatives from a wide range of federal agencies.
 

Key changes

Christina Nelson, a medical officer with the CDC’s Division of Vector-Borne Diseases, told this news organization that now “we have been fortunate to have extended options for treatment.” Previously, “streptomycin and gentamicin were the first-line options for adults,” she said. Now, on the basis of additional evidence, “[we’re] able to … elevate the fluoroquinolones to first-line treatments.”

On the basis of the Animal Rule, which allows approval of antibiotics without human testing if such testing is not possible, the U.S. Food and Drug Administration has approved several quinolones for both treatment and prophylaxis of plague.

The guidelines offer same-class alternative antibiotics to meet surge capacity. Similarly, trimethoprim-sulfamethoxazole is now an alternative for prophylaxis.

There are additional oral options to conserve IV medications and supplies in a mass casualty event.

For the first time, the CDC added specific recommendations for pregnant women. Gigi Kwik Gronvall, PhD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, told this news organization that she was pleased to see this addition, because “effects on women and during pregnancy are not fully addressed, and it leads to problems down the road, like with COVID, [for which] they didn’t include pregnant people in their clinical trials for the vaccines [and] don’t have enough data to convince pregnant women to actually get the vaccine.”
 

Bubonic plague

Plague occurs globally, with natural sylvatic (wild animal) outbreaks occurring among rodents and small mammals. It is spread by fleas. When an infected flea bites a human, the person can become infected, most commonly as “bubonic” plague, with swollen lymph nodes, called buboes. Transmission can also occur between people by contact with infected fluids or inhalation of infectious droplets.

Gentamicin or streptomycin remain first-line agents for treating bubonic plague. When used as monotherapy, the survival rate is 91%. They have to be given parenterally and are associated with both nephroroxicity and ototoxicity; patients require monitoring.

Alternative first-line drugs now include high-dose ciprofloxicin, levofloxacin, moxifloxacin, and doxycycline. Each is administered either intravenously or orally.

Physicians should consider dual therapy and drainage for patients with large buboes. Treatment is for 10 to 14 days.
 

Pneumonic and septicemic plague

The pneumonic and septicemic forms of infection are deadlier than the bubonic. Pneumonic plague can be acquired from inhalation of infected bacteria from animals or people, from lab accidents, or from intentional aerosolization. Without treatment, these forms are almost always fatal. With treatment with aminoglycosides, fluoroquinolones, or tetracyclines, alone or in combination, survival is 82% to 83%. With naturally occurring pneumonic plague, the CDC now recommends levofloxacin or moxifloxacin to cover for community-acquired pneumonia if the source of the infection is uncertain.

Because plague is life threatening, doxycycline is not considered contraindicated in children. It has not been shown to cause tooth staining, unlike other tetracyclines, which should still be avoided if possible.
 

Meningitis

About 10% of people infected with bubonic plague develop plague meningitis. Symptoms are stiff neck, fever, headache, and coma. The current recommendation for treating plague meningitis is chloramphenicol and moxifloxacin or levofloxacin. However, quinolones can cause seizures, and clinicians should take that into account.

Infection control

Plague is transmitted between people by droplets, so caretakers should wear a mask in addition to taking standard precautions. They should add eye protection and a face shield if splashing is likely. Airborne precautions are not needed. Plague is not very transmissible from person to person; each infected person on average infects only 1.18 other people. In comparison, someone with chicken pox infects 9 to 10 people on average.

Bioterrorism

A deliberate attack would likely go undetected until a cluster or unusual pattern of disease became evident. With Y. pestis, the infectious dose is low. According to the guidelines, modeling suggests that a “release of 50 kg of Y. pestis into the air over a city of 5 million persons could result in 150,000 cases of pneumonic plague and 36,000 deaths.”

Because the former Union of the Soviet Socialist Republics (USSR) engineered antibiotic-resistant Y. pestis, antibiotics from two different classes should be used empirically until sensitivity tests become available.

Antibiotic prophylaxis would also have to be considered for exposed individuals. Recommendations would be developed at the time by federal and state experts, based in part on the magnitude of the event and the availability of masks and different classes of antibiotics.

Dr. Gronvall stressed the need for awareness, saying, “It’s important for people to remember that the first sign of the potential attack could be somebody coming into your hospital.”

Dr. Nelson added, “One of the main take-home messages ... is that plague still happens, it still happens in the western United States, it still happens around the world ... It’s not just a relic of history.” She emphasized that clinicians need to be thinking about it, because “it’s very important to get antibiotics on board early ... Then patients generally have a good prognosis.”

Dr. Nelson and Dr. Gronvall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Administering hyperimmune globulin to pregnant women who tested positive for cytomegalovirus did not reduce CMV infections or deaths among their fetuses or newborns, according to a randomized controlled trial published online July 28 in the New England Journal of Medicine.

Up to 40,000 infants a year have congenital CMV infections, which can lead to stillbirth, neonatal death, deafness, and cognitive and motor delay. An estimated 35%-40% of fetuses of women with a primary CMV infection will develop an infection, write Brenna Hughes, MD, an associate professor of ob/gyn and chief of the division of maternal fetal medicine at Duke University, Durham, N.C., and colleagues.

Previous trials and observational studies have shown mixed results with hyperimmune globulin for the prevention of congenital CMV infection.

“It was surprising to us that none of the outcomes in this trial were in the direction of potential benefit,” Dr. Hughes told this news organization. “However, this is why it is important to do large trials in a diverse population.”

The study cohort comprised 206,082 pregnant women who were screened for CMV infection before 23 weeks’ gestation. Of those women, 712 (0.35%) tested positive for CMV. The researchers enrolled 399 women who had tested positive and randomly assigned them to receive either a monthly infusion of CMV hyperimmune globulin (100 mg/kg) or placebo until delivery. The researchers used a composite of CMV infection or, if no testing occurred, fetal/neonatal death as the primary endpoint.

The trial was stopped early for futility when data from 394 participants revealed that 22.7% of offspring in the hyperimmune globulin group and 19.4% of those in the placebo group had had a CMV infection or had died (relative risk = 1.17; P = .42).

When individual endpoints were examined, trends were detected in favor of the placebo, but they did not reach statistical significance. The incidence of death was higher in the hyperimmune globulin group (4.9%) than in the placebo group (2.6%). The rate of preterm birth was also higher in the intervention group (12.2%) than in the group that received placebo (8.3%). The incidence of birth weight below the fifth percentile was 10.3% in the intervention group and 5.4% in the placebo group.

One woman who received hyperimmune globulin experienced a severe allergic reaction to the first infusion. Additionally, more women in the hyperimmune globulin group experienced headaches and shaking chills during infusions than did those who received placebo. There were no differences in maternal outcomes between the groups. There were no thromboembolic or ischemic events in either group.

“These findings suggest CMV hyperimmune globulin should not be used for the prevention of congenital CMV in pregnant patients with primary CMV during pregnancy,” Dr. Hughes said in an interview.

“A CMV vaccine is likely to be the most effective public health measure that we can offer, and that should be at the forefront of research investments,” she said. “But some of the other medications that work against CMV should be tested on a large scale as well,” she said. For example, a small trial in Israel showed that high-dose valacyclovir in early pregnancy decreased congenital CMV, and thus the drug merits study in a larger trial, she said.

Other experts agree that developing a vaccine should be the priority.

“The ultimate goal for preventing the brain damage and birth defects caused by congenital CMV infection is a vaccine that is as effective as the rubella vaccine has been for eliminating congenital rubella syndrome and that can be given well before pregnancy,” said Sallie Permar, MD, PhD, chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at New York–Presbyterian/Weill Cornell Medical Center and the New York–Presbyterian Komansky Children’s Hospital in New York.

“While trials of vaccines are ongoing, there is a need to have a therapeutic option, especially for the high-risk setting of a mother acquiring the virus for the first time during pregnancy,” Dr. Permar said in an interview.

Dr. Permar was not involved in this study but is involved in follow-up studies of this cohort and is conducting research on CMV maternal vaccines. She noted the need for safe, effective antiviral treatments and for research into newer immunoglobulin products, such as monoclonal antibodies.

Both Dr. Permar and Dr. Hughes highlighted the challenge of raising awareness about the danger of CMV infections during pregnancy.

“Pregnant women, and especially those who have or work with young children, who are frequently carriers of the infection, should be informed of this risk,” Dr. Permar said. She hopes universal testing of newborns will be implemented and that it enables people to recognize the frequency and burden of these infections. She remains optimistic about a vaccine.

“After 60 years of research into a CMV vaccine, I believe we are currently in a ‘golden age’ of CMV vaccine development,” she said. She noted that Moderna is about to launch a phase 3 mRNA vaccine trial for CMV. “Moreover, immune correlates of protection against CMV have been identified from previous partially effective vaccines, and animal models have improved for preclinical studies. Therefore, I believe we will have an effective and safe vaccine against this most common congenital infection in the coming years.”

The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Dr. Hughes has served on Merck’s scientific advisory board. Various coauthors have received personal fees from Medela and nonfinancial support from Hologic; personal fees from Moderna and VBI vaccines, and grants from Novavax. Dr. Permar consults for Pfizer, Moderna, Merck, Sanofi, and Dynavax on their CMV vaccine programs, and she has a sponsored research program with Merck and Moderna on CMV vaccines.

A version of this article first appeared on Medscape.com.

Administering hyperimmune globulin to pregnant women who tested positive for cytomegalovirus did not reduce CMV infections or deaths among their fetuses or newborns, according to a randomized controlled trial published online July 28 in the New England Journal of Medicine.

Up to 40,000 infants a year have congenital CMV infections, which can lead to stillbirth, neonatal death, deafness, and cognitive and motor delay. An estimated 35%-40% of fetuses of women with a primary CMV infection will develop an infection, write Brenna Hughes, MD, an associate professor of ob/gyn and chief of the division of maternal fetal medicine at Duke University, Durham, N.C., and colleagues.

Previous trials and observational studies have shown mixed results with hyperimmune globulin for the prevention of congenital CMV infection.

“It was surprising to us that none of the outcomes in this trial were in the direction of potential benefit,” Dr. Hughes told this news organization. “However, this is why it is important to do large trials in a diverse population.”

The study cohort comprised 206,082 pregnant women who were screened for CMV infection before 23 weeks’ gestation. Of those women, 712 (0.35%) tested positive for CMV. The researchers enrolled 399 women who had tested positive and randomly assigned them to receive either a monthly infusion of CMV hyperimmune globulin (100 mg/kg) or placebo until delivery. The researchers used a composite of CMV infection or, if no testing occurred, fetal/neonatal death as the primary endpoint.

The trial was stopped early for futility when data from 394 participants revealed that 22.7% of offspring in the hyperimmune globulin group and 19.4% of those in the placebo group had had a CMV infection or had died (relative risk = 1.17; P = .42).

When individual endpoints were examined, trends were detected in favor of the placebo, but they did not reach statistical significance. The incidence of death was higher in the hyperimmune globulin group (4.9%) than in the placebo group (2.6%). The rate of preterm birth was also higher in the intervention group (12.2%) than in the group that received placebo (8.3%). The incidence of birth weight below the fifth percentile was 10.3% in the intervention group and 5.4% in the placebo group.

One woman who received hyperimmune globulin experienced a severe allergic reaction to the first infusion. Additionally, more women in the hyperimmune globulin group experienced headaches and shaking chills during infusions than did those who received placebo. There were no differences in maternal outcomes between the groups. There were no thromboembolic or ischemic events in either group.

“These findings suggest CMV hyperimmune globulin should not be used for the prevention of congenital CMV in pregnant patients with primary CMV during pregnancy,” Dr. Hughes said in an interview.

“A CMV vaccine is likely to be the most effective public health measure that we can offer, and that should be at the forefront of research investments,” she said. “But some of the other medications that work against CMV should be tested on a large scale as well,” she said. For example, a small trial in Israel showed that high-dose valacyclovir in early pregnancy decreased congenital CMV, and thus the drug merits study in a larger trial, she said.

Other experts agree that developing a vaccine should be the priority.

“The ultimate goal for preventing the brain damage and birth defects caused by congenital CMV infection is a vaccine that is as effective as the rubella vaccine has been for eliminating congenital rubella syndrome and that can be given well before pregnancy,” said Sallie Permar, MD, PhD, chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at New York–Presbyterian/Weill Cornell Medical Center and the New York–Presbyterian Komansky Children’s Hospital in New York.

“While trials of vaccines are ongoing, there is a need to have a therapeutic option, especially for the high-risk setting of a mother acquiring the virus for the first time during pregnancy,” Dr. Permar said in an interview.

Dr. Permar was not involved in this study but is involved in follow-up studies of this cohort and is conducting research on CMV maternal vaccines. She noted the need for safe, effective antiviral treatments and for research into newer immunoglobulin products, such as monoclonal antibodies.

Both Dr. Permar and Dr. Hughes highlighted the challenge of raising awareness about the danger of CMV infections during pregnancy.

“Pregnant women, and especially those who have or work with young children, who are frequently carriers of the infection, should be informed of this risk,” Dr. Permar said. She hopes universal testing of newborns will be implemented and that it enables people to recognize the frequency and burden of these infections. She remains optimistic about a vaccine.

“After 60 years of research into a CMV vaccine, I believe we are currently in a ‘golden age’ of CMV vaccine development,” she said. She noted that Moderna is about to launch a phase 3 mRNA vaccine trial for CMV. “Moreover, immune correlates of protection against CMV have been identified from previous partially effective vaccines, and animal models have improved for preclinical studies. Therefore, I believe we will have an effective and safe vaccine against this most common congenital infection in the coming years.”

The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Dr. Hughes has served on Merck’s scientific advisory board. Various coauthors have received personal fees from Medela and nonfinancial support from Hologic; personal fees from Moderna and VBI vaccines, and grants from Novavax. Dr. Permar consults for Pfizer, Moderna, Merck, Sanofi, and Dynavax on their CMV vaccine programs, and she has a sponsored research program with Merck and Moderna on CMV vaccines.

A version of this article first appeared on Medscape.com.

Administering hyperimmune globulin to pregnant women who tested positive for cytomegalovirus did not reduce CMV infections or deaths among their fetuses or newborns, according to a randomized controlled trial published online July 28 in the New England Journal of Medicine.

Up to 40,000 infants a year have congenital CMV infections, which can lead to stillbirth, neonatal death, deafness, and cognitive and motor delay. An estimated 35%-40% of fetuses of women with a primary CMV infection will develop an infection, write Brenna Hughes, MD, an associate professor of ob/gyn and chief of the division of maternal fetal medicine at Duke University, Durham, N.C., and colleagues.

Previous trials and observational studies have shown mixed results with hyperimmune globulin for the prevention of congenital CMV infection.

“It was surprising to us that none of the outcomes in this trial were in the direction of potential benefit,” Dr. Hughes told this news organization. “However, this is why it is important to do large trials in a diverse population.”

The study cohort comprised 206,082 pregnant women who were screened for CMV infection before 23 weeks’ gestation. Of those women, 712 (0.35%) tested positive for CMV. The researchers enrolled 399 women who had tested positive and randomly assigned them to receive either a monthly infusion of CMV hyperimmune globulin (100 mg/kg) or placebo until delivery. The researchers used a composite of CMV infection or, if no testing occurred, fetal/neonatal death as the primary endpoint.

The trial was stopped early for futility when data from 394 participants revealed that 22.7% of offspring in the hyperimmune globulin group and 19.4% of those in the placebo group had had a CMV infection or had died (relative risk = 1.17; P = .42).

When individual endpoints were examined, trends were detected in favor of the placebo, but they did not reach statistical significance. The incidence of death was higher in the hyperimmune globulin group (4.9%) than in the placebo group (2.6%). The rate of preterm birth was also higher in the intervention group (12.2%) than in the group that received placebo (8.3%). The incidence of birth weight below the fifth percentile was 10.3% in the intervention group and 5.4% in the placebo group.

One woman who received hyperimmune globulin experienced a severe allergic reaction to the first infusion. Additionally, more women in the hyperimmune globulin group experienced headaches and shaking chills during infusions than did those who received placebo. There were no differences in maternal outcomes between the groups. There were no thromboembolic or ischemic events in either group.

“These findings suggest CMV hyperimmune globulin should not be used for the prevention of congenital CMV in pregnant patients with primary CMV during pregnancy,” Dr. Hughes said in an interview.

“A CMV vaccine is likely to be the most effective public health measure that we can offer, and that should be at the forefront of research investments,” she said. “But some of the other medications that work against CMV should be tested on a large scale as well,” she said. For example, a small trial in Israel showed that high-dose valacyclovir in early pregnancy decreased congenital CMV, and thus the drug merits study in a larger trial, she said.

Other experts agree that developing a vaccine should be the priority.

“The ultimate goal for preventing the brain damage and birth defects caused by congenital CMV infection is a vaccine that is as effective as the rubella vaccine has been for eliminating congenital rubella syndrome and that can be given well before pregnancy,” said Sallie Permar, MD, PhD, chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at New York–Presbyterian/Weill Cornell Medical Center and the New York–Presbyterian Komansky Children’s Hospital in New York.

“While trials of vaccines are ongoing, there is a need to have a therapeutic option, especially for the high-risk setting of a mother acquiring the virus for the first time during pregnancy,” Dr. Permar said in an interview.

Dr. Permar was not involved in this study but is involved in follow-up studies of this cohort and is conducting research on CMV maternal vaccines. She noted the need for safe, effective antiviral treatments and for research into newer immunoglobulin products, such as monoclonal antibodies.

Both Dr. Permar and Dr. Hughes highlighted the challenge of raising awareness about the danger of CMV infections during pregnancy.

“Pregnant women, and especially those who have or work with young children, who are frequently carriers of the infection, should be informed of this risk,” Dr. Permar said. She hopes universal testing of newborns will be implemented and that it enables people to recognize the frequency and burden of these infections. She remains optimistic about a vaccine.

“After 60 years of research into a CMV vaccine, I believe we are currently in a ‘golden age’ of CMV vaccine development,” she said. She noted that Moderna is about to launch a phase 3 mRNA vaccine trial for CMV. “Moreover, immune correlates of protection against CMV have been identified from previous partially effective vaccines, and animal models have improved for preclinical studies. Therefore, I believe we will have an effective and safe vaccine against this most common congenital infection in the coming years.”

The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Dr. Hughes has served on Merck’s scientific advisory board. Various coauthors have received personal fees from Medela and nonfinancial support from Hologic; personal fees from Moderna and VBI vaccines, and grants from Novavax. Dr. Permar consults for Pfizer, Moderna, Merck, Sanofi, and Dynavax on their CMV vaccine programs, and she has a sponsored research program with Merck and Moderna on CMV vaccines.

A version of this article first appeared on Medscape.com.

Noopur Raje, MD, has been sitting at home for 5 weeks waiting for her COVID-19 test to turn negative so she can get back to work. She’s a cancer specialist – head of the Massachusetts General Hospital’s Center for Multiple Myeloma – but Raje says as soon as she’s allowed back to the hospital, she’ll head straight to the front line of COVID-19 caregivers.

“It’s people like us who have to get back in the trenches and do the work now,” she told Medscape Medical News.

“I still will be at risk,” she said. But, having nursed her physician husband through COVID-19 at home until he was admitted to an intensive care unit, she is determined to help in the COVID-19 wards.

“I will be the first one to volunteer to take care of these patients,” she said. “I can’t wait, as I want to give these folks hope. They are so scared.”

Around the world, it’s assumed that she and others like her who’ve recovered from COVID-19 will be immune to the infection.

Some have suggested that with antibodies to the virus coursing through their veins, these survivors might be given immunity passports. They could be the ones to jump-start people’s lives again ― the first to be let out from lockdown, and in healthcare, the ones to head the ongoing battle against this pandemic.

So, there has been a race to develop COVID-19 antibody tests to identify these people.
 

Circumventing the Usual Clearance Process

To speed up the process, the US Food and Drug Administration (FDA) made a much-criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not gone through the agency’s usual evaluation process. The result was a flood of more than 90 unapproved tests “that have, frankly, dubious quality,” said Scott Becker, CEO of the Association of Public Health Laboratories (APHL), which represents local and state public laboratories.

The APHL spoke out in dismay – its chief program officer, Eric Blank, decried the “Wild West” of tests unleashed on the public.

“These tests create more uncertainty than before,” said Kelly Wroblewski, APHL’s director of infectious diseases, in a news conference on April 14. “Having many inaccurate tests is worse than having no tests at all.”

The APHL and the FDA, working with the Centers for Disease Control and Prevention and the National Institutes of Health (NIH), have moved quickly into damage control, conducting evaluations of the tests in an effort to distinguish the potentially useful from the useless.

So far, they have succeeded in issuing emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

For all the other antibody tests on the market that do not have an EUA, “They’re trusting that the test developer has done a good job in validation,” Becker said. But there are worrying anecdotes. “Our members have reported that they’ve seen fraudulent marketing.... We’ve seen the FDA clamp down on some companies... [and] a number of cities and health departments have issued warnings because of what they’ve seen,” he added.

In particular, Wroblewski said, some companies are marketing tests for use in physicians’ offices or pharmacies. “Today, there are no serology tests approved for point-of-care settings,” she warned. “We don’t know how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.”
 

Uncertainty Emphasized

The FDA emphasized the uncertainty about antibody tests in a statement released on April 18.

Although the tests can identify people who have been exposed and who developed an immune response to the virus, the agency noted, “we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts.”

The FDA says that the role of these antibody tests, at present, lies in providing information to “help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward.”

The World Health Organization (WHO) also emphasized the current uncertainty over antibody tests at a press briefing on April 17. “Nobody is sure about the length of protection that antibodies may give and whether they fully protect against ... the disease,” said Mike Ryan, MD, executive director of the WHO’s emergencies program. There is also a concern that such tests may give false assurance or be misused. “There is still a lot of work that needs to be done to validate these antibody tests,” he added.

“The WHO are right to highlight that any antibody test, if we get one, won’t be able to definitely say whether someone is immune to the infection, because we just don’t know enough yet about how immunity works with COVID-19,” commented Prof. Chris Dye, Oxford Martin School, University of Oxford, in reaction on the UK Science Media Center.

Expanding on this point on the same site, Andrew Easton PhD, professor of virology at the University of Warwick, noted that “a serology test does not discriminate between neutralising and non-neutralising antibodies; a discriminatory test is much more complex and slow.”

Only the neutralizing antibodies have the ability to inactivate the invading virus, he noted.

“When people are infected, the proportions of neutralising and non-neutralising antibodies can differ. It is not always understood what makes an antibody neutralising and another non-neutralising, or why an infection leads to production of more of one of these types of antibodies,” he explained. “The initial immune response immediately following infection sets the memory of the immune system, so if the person had generated mostly non-neutralising antibodies, the next time that person encounters the same virus, they may not be able to prevent an infection.”

So at present, the information from antibody testing is largely unhelpful to individuals, but it could be valuable to epidemiologists and policy makers.

“States are looking at ways they can integrate reliable serologic tests for surveillance,” explained APHL’s Blank.

Knowing how widespread the infection has been within a community could guide research and possibly public health decisions, Wroblewski said at the APHL press conference. But she’s hesitant here, too. “I know there has been a lot of talk about using this testing to ease restrictions, but I do think we need to be cautious on how quickly we move in that direction.” If people don’t have antibodies, it means they haven’t been exposed and that they’re still vulnerable, she noted. “If nothing else, that still informs policy decisions, even if they’re not the policy decisions we want.”
 

Trials Recruiting, Medical Centers Develop Own Tests

Despite the uncertainties over antibody testing, many efforts are still being guided by this strategy.

The NIH is recruiting volunteers to its antibody testing study and suggests that immunity is “likely” for those who test positive.

In addition, several large medical centers have developed their own antibody tests, including Stanford, the Yale New Haven Hospital, and the Mayo Clinic.

The Stanford test detects two types of antibodies: IgM, which is made early in an immune response and usually wanes quickly, and IgG, which rises more slowly after infection but usually persists longer.

“There’s limited data out of China and Europe showing that this appears to be the response pattern followed with this virus,” commented Thomas Montine, MD, PhD, professor and chair of pathology at Stanford University. “But no one has had this long enough to know how long after infection the antibodies persist,” he added.

“There is enormous demand for serologic testing,” said William Morice, MD, PhD, president of Mayo Clinic Laboratories. “At this time, serology testing needs to be prioritized for efforts to identify individuals in areas where potential immunity is key ― supporting healthcare workers, screening for potential plasma donors, and helping advance the most promising vaccine candidates.”

During a recent webinar with the Association for Value-Based Cancer Care, the largest physician-owned oncology-hematology practice in the country, the president, Lucio Gordan, MD, said his organization was looking into antibody testing for staff. “They wanted to see how many have been exposed,” he said, although “what it means is uncertain.”

When Medscape Medical News checked back with him a few weeks later, Gordan, president of Florida Cancer Specialists and Research Institute, reported that no progress had been made.

“We unfortunately have not been able to test yet, due to concerns with reliability of kits. We are waiting for a better solution so we can reassess our strategy,” he said.

This article first appeared on Medscape.com.

Noopur Raje, MD, has been sitting at home for 5 weeks waiting for her COVID-19 test to turn negative so she can get back to work. She’s a cancer specialist – head of the Massachusetts General Hospital’s Center for Multiple Myeloma – but Raje says as soon as she’s allowed back to the hospital, she’ll head straight to the front line of COVID-19 caregivers.

“It’s people like us who have to get back in the trenches and do the work now,” she told Medscape Medical News.

“I still will be at risk,” she said. But, having nursed her physician husband through COVID-19 at home until he was admitted to an intensive care unit, she is determined to help in the COVID-19 wards.

“I will be the first one to volunteer to take care of these patients,” she said. “I can’t wait, as I want to give these folks hope. They are so scared.”

Around the world, it’s assumed that she and others like her who’ve recovered from COVID-19 will be immune to the infection.

Some have suggested that with antibodies to the virus coursing through their veins, these survivors might be given immunity passports. They could be the ones to jump-start people’s lives again ― the first to be let out from lockdown, and in healthcare, the ones to head the ongoing battle against this pandemic.

So, there has been a race to develop COVID-19 antibody tests to identify these people.
 

Circumventing the Usual Clearance Process

To speed up the process, the US Food and Drug Administration (FDA) made a much-criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not gone through the agency’s usual evaluation process. The result was a flood of more than 90 unapproved tests “that have, frankly, dubious quality,” said Scott Becker, CEO of the Association of Public Health Laboratories (APHL), which represents local and state public laboratories.

The APHL spoke out in dismay – its chief program officer, Eric Blank, decried the “Wild West” of tests unleashed on the public.

“These tests create more uncertainty than before,” said Kelly Wroblewski, APHL’s director of infectious diseases, in a news conference on April 14. “Having many inaccurate tests is worse than having no tests at all.”

The APHL and the FDA, working with the Centers for Disease Control and Prevention and the National Institutes of Health (NIH), have moved quickly into damage control, conducting evaluations of the tests in an effort to distinguish the potentially useful from the useless.

So far, they have succeeded in issuing emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

For all the other antibody tests on the market that do not have an EUA, “They’re trusting that the test developer has done a good job in validation,” Becker said. But there are worrying anecdotes. “Our members have reported that they’ve seen fraudulent marketing.... We’ve seen the FDA clamp down on some companies... [and] a number of cities and health departments have issued warnings because of what they’ve seen,” he added.

In particular, Wroblewski said, some companies are marketing tests for use in physicians’ offices or pharmacies. “Today, there are no serology tests approved for point-of-care settings,” she warned. “We don’t know how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.”
 

Uncertainty Emphasized

The FDA emphasized the uncertainty about antibody tests in a statement released on April 18.

Although the tests can identify people who have been exposed and who developed an immune response to the virus, the agency noted, “we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts.”

The FDA says that the role of these antibody tests, at present, lies in providing information to “help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward.”

The World Health Organization (WHO) also emphasized the current uncertainty over antibody tests at a press briefing on April 17. “Nobody is sure about the length of protection that antibodies may give and whether they fully protect against ... the disease,” said Mike Ryan, MD, executive director of the WHO’s emergencies program. There is also a concern that such tests may give false assurance or be misused. “There is still a lot of work that needs to be done to validate these antibody tests,” he added.

“The WHO are right to highlight that any antibody test, if we get one, won’t be able to definitely say whether someone is immune to the infection, because we just don’t know enough yet about how immunity works with COVID-19,” commented Prof. Chris Dye, Oxford Martin School, University of Oxford, in reaction on the UK Science Media Center.

Expanding on this point on the same site, Andrew Easton PhD, professor of virology at the University of Warwick, noted that “a serology test does not discriminate between neutralising and non-neutralising antibodies; a discriminatory test is much more complex and slow.”

Only the neutralizing antibodies have the ability to inactivate the invading virus, he noted.

“When people are infected, the proportions of neutralising and non-neutralising antibodies can differ. It is not always understood what makes an antibody neutralising and another non-neutralising, or why an infection leads to production of more of one of these types of antibodies,” he explained. “The initial immune response immediately following infection sets the memory of the immune system, so if the person had generated mostly non-neutralising antibodies, the next time that person encounters the same virus, they may not be able to prevent an infection.”

So at present, the information from antibody testing is largely unhelpful to individuals, but it could be valuable to epidemiologists and policy makers.

“States are looking at ways they can integrate reliable serologic tests for surveillance,” explained APHL’s Blank.

Knowing how widespread the infection has been within a community could guide research and possibly public health decisions, Wroblewski said at the APHL press conference. But she’s hesitant here, too. “I know there has been a lot of talk about using this testing to ease restrictions, but I do think we need to be cautious on how quickly we move in that direction.” If people don’t have antibodies, it means they haven’t been exposed and that they’re still vulnerable, she noted. “If nothing else, that still informs policy decisions, even if they’re not the policy decisions we want.”
 

Trials Recruiting, Medical Centers Develop Own Tests

Despite the uncertainties over antibody testing, many efforts are still being guided by this strategy.

The NIH is recruiting volunteers to its antibody testing study and suggests that immunity is “likely” for those who test positive.

In addition, several large medical centers have developed their own antibody tests, including Stanford, the Yale New Haven Hospital, and the Mayo Clinic.

The Stanford test detects two types of antibodies: IgM, which is made early in an immune response and usually wanes quickly, and IgG, which rises more slowly after infection but usually persists longer.

“There’s limited data out of China and Europe showing that this appears to be the response pattern followed with this virus,” commented Thomas Montine, MD, PhD, professor and chair of pathology at Stanford University. “But no one has had this long enough to know how long after infection the antibodies persist,” he added.

“There is enormous demand for serologic testing,” said William Morice, MD, PhD, president of Mayo Clinic Laboratories. “At this time, serology testing needs to be prioritized for efforts to identify individuals in areas where potential immunity is key ― supporting healthcare workers, screening for potential plasma donors, and helping advance the most promising vaccine candidates.”

During a recent webinar with the Association for Value-Based Cancer Care, the largest physician-owned oncology-hematology practice in the country, the president, Lucio Gordan, MD, said his organization was looking into antibody testing for staff. “They wanted to see how many have been exposed,” he said, although “what it means is uncertain.”

When Medscape Medical News checked back with him a few weeks later, Gordan, president of Florida Cancer Specialists and Research Institute, reported that no progress had been made.

“We unfortunately have not been able to test yet, due to concerns with reliability of kits. We are waiting for a better solution so we can reassess our strategy,” he said.

This article first appeared on Medscape.com.

Noopur Raje, MD, has been sitting at home for 5 weeks waiting for her COVID-19 test to turn negative so she can get back to work. She’s a cancer specialist – head of the Massachusetts General Hospital’s Center for Multiple Myeloma – but Raje says as soon as she’s allowed back to the hospital, she’ll head straight to the front line of COVID-19 caregivers.

“It’s people like us who have to get back in the trenches and do the work now,” she told Medscape Medical News.

“I still will be at risk,” she said. But, having nursed her physician husband through COVID-19 at home until he was admitted to an intensive care unit, she is determined to help in the COVID-19 wards.

“I will be the first one to volunteer to take care of these patients,” she said. “I can’t wait, as I want to give these folks hope. They are so scared.”

Around the world, it’s assumed that she and others like her who’ve recovered from COVID-19 will be immune to the infection.

Some have suggested that with antibodies to the virus coursing through their veins, these survivors might be given immunity passports. They could be the ones to jump-start people’s lives again ― the first to be let out from lockdown, and in healthcare, the ones to head the ongoing battle against this pandemic.

So, there has been a race to develop COVID-19 antibody tests to identify these people.
 

Circumventing the Usual Clearance Process

To speed up the process, the US Food and Drug Administration (FDA) made a much-criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not gone through the agency’s usual evaluation process. The result was a flood of more than 90 unapproved tests “that have, frankly, dubious quality,” said Scott Becker, CEO of the Association of Public Health Laboratories (APHL), which represents local and state public laboratories.

The APHL spoke out in dismay – its chief program officer, Eric Blank, decried the “Wild West” of tests unleashed on the public.

“These tests create more uncertainty than before,” said Kelly Wroblewski, APHL’s director of infectious diseases, in a news conference on April 14. “Having many inaccurate tests is worse than having no tests at all.”

The APHL and the FDA, working with the Centers for Disease Control and Prevention and the National Institutes of Health (NIH), have moved quickly into damage control, conducting evaluations of the tests in an effort to distinguish the potentially useful from the useless.

So far, they have succeeded in issuing emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory.

For all the other antibody tests on the market that do not have an EUA, “They’re trusting that the test developer has done a good job in validation,” Becker said. But there are worrying anecdotes. “Our members have reported that they’ve seen fraudulent marketing.... We’ve seen the FDA clamp down on some companies... [and] a number of cities and health departments have issued warnings because of what they’ve seen,” he added.

In particular, Wroblewski said, some companies are marketing tests for use in physicians’ offices or pharmacies. “Today, there are no serology tests approved for point-of-care settings,” she warned. “We don’t know how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.”
 

Uncertainty Emphasized

The FDA emphasized the uncertainty about antibody tests in a statement released on April 18.

Although the tests can identify people who have been exposed and who developed an immune response to the virus, the agency noted, “we don’t yet know that just because someone has developed antibodies, that they are fully protected from reinfection, or how long any immunity lasts.”

The FDA says that the role of these antibody tests, at present, lies in providing information to “help us track the spread of the virus nationwide and assess the impact of our public health efforts now, while also informing our COVID-19 response as we continue to move forward.”

The World Health Organization (WHO) also emphasized the current uncertainty over antibody tests at a press briefing on April 17. “Nobody is sure about the length of protection that antibodies may give and whether they fully protect against ... the disease,” said Mike Ryan, MD, executive director of the WHO’s emergencies program. There is also a concern that such tests may give false assurance or be misused. “There is still a lot of work that needs to be done to validate these antibody tests,” he added.

“The WHO are right to highlight that any antibody test, if we get one, won’t be able to definitely say whether someone is immune to the infection, because we just don’t know enough yet about how immunity works with COVID-19,” commented Prof. Chris Dye, Oxford Martin School, University of Oxford, in reaction on the UK Science Media Center.

Expanding on this point on the same site, Andrew Easton PhD, professor of virology at the University of Warwick, noted that “a serology test does not discriminate between neutralising and non-neutralising antibodies; a discriminatory test is much more complex and slow.”

Only the neutralizing antibodies have the ability to inactivate the invading virus, he noted.

“When people are infected, the proportions of neutralising and non-neutralising antibodies can differ. It is not always understood what makes an antibody neutralising and another non-neutralising, or why an infection leads to production of more of one of these types of antibodies,” he explained. “The initial immune response immediately following infection sets the memory of the immune system, so if the person had generated mostly non-neutralising antibodies, the next time that person encounters the same virus, they may not be able to prevent an infection.”

So at present, the information from antibody testing is largely unhelpful to individuals, but it could be valuable to epidemiologists and policy makers.

“States are looking at ways they can integrate reliable serologic tests for surveillance,” explained APHL’s Blank.

Knowing how widespread the infection has been within a community could guide research and possibly public health decisions, Wroblewski said at the APHL press conference. But she’s hesitant here, too. “I know there has been a lot of talk about using this testing to ease restrictions, but I do think we need to be cautious on how quickly we move in that direction.” If people don’t have antibodies, it means they haven’t been exposed and that they’re still vulnerable, she noted. “If nothing else, that still informs policy decisions, even if they’re not the policy decisions we want.”
 

Trials Recruiting, Medical Centers Develop Own Tests

Despite the uncertainties over antibody testing, many efforts are still being guided by this strategy.

The NIH is recruiting volunteers to its antibody testing study and suggests that immunity is “likely” for those who test positive.

In addition, several large medical centers have developed their own antibody tests, including Stanford, the Yale New Haven Hospital, and the Mayo Clinic.

The Stanford test detects two types of antibodies: IgM, which is made early in an immune response and usually wanes quickly, and IgG, which rises more slowly after infection but usually persists longer.

“There’s limited data out of China and Europe showing that this appears to be the response pattern followed with this virus,” commented Thomas Montine, MD, PhD, professor and chair of pathology at Stanford University. “But no one has had this long enough to know how long after infection the antibodies persist,” he added.

“There is enormous demand for serologic testing,” said William Morice, MD, PhD, president of Mayo Clinic Laboratories. “At this time, serology testing needs to be prioritized for efforts to identify individuals in areas where potential immunity is key ― supporting healthcare workers, screening for potential plasma donors, and helping advance the most promising vaccine candidates.”

During a recent webinar with the Association for Value-Based Cancer Care, the largest physician-owned oncology-hematology practice in the country, the president, Lucio Gordan, MD, said his organization was looking into antibody testing for staff. “They wanted to see how many have been exposed,” he said, although “what it means is uncertain.”

When Medscape Medical News checked back with him a few weeks later, Gordan, president of Florida Cancer Specialists and Research Institute, reported that no progress had been made.

“We unfortunately have not been able to test yet, due to concerns with reliability of kits. We are waiting for a better solution so we can reassess our strategy,” he said.

This article first appeared on Medscape.com.

Adults are interested in a dengue vaccine for themselves and their children, and physicians recognize that dengue is a public health problem, according to data from parents and physicians in Puerto Rico. Most doctors, but fewer parents, found the idea of protecting children with Dengue vaccine acceptable.

itsmejust/Thinkstock

Lack of detailed information about the vaccine is the greatest barrier to parents’ consent to vaccination, noted Ines Esquilin, MD, of the University of Puerto Rico, San Juan, in a presentation at the February meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The ACIP dengue vaccines work group reviewed data from 102 physicians in Puerto Rico, 82% of which were pediatricians, regarding potential dengue vaccination. Overall, 98% said they considered dengue a significant public health problem in Puerto Rico, and 73% said they would recommend the dengue vaccine to patients if a laboratory test with acceptable specificity were available. Among the physicians who said they would not recommend the vaccine, the most common reason (71%) was concern about the risks of vaccinating individuals with false-positive tests.

The availability of a test that can be performed in the medical office and avoid repeat visits is a major factor in the feasibility of dengue vaccination, Dr. Esquilin said.

The ACIP dengue vaccines work group also sought public opinion on the acceptability of a generic dengue vaccine through focus group sessions with parents of children aged 9-16 years in Puerto Rico, said Dr. Esquilin.

Approximately one-third of the parents said they were willing to vaccinate their children, one-third were unwilling, and one-third were unsure. The most commonly identified barriers to vaccination included lack of information or inconsistent information about the vaccine, high cost/lack of insurance coverage, time-consuming lab test to confirm infection, side effects, potential for false-positive lab results, and low vaccine effectiveness.

Motivating factors for vaccination included correct information about the vaccine, desire to prevent infection, lab-confirmed positive test, support from public health organizations, the presence of a dengue epidemic, and educational forums.

Based in part on these findings, the ACIP dengue vaccines work group noted that the need for an acceptably specific screening lab test is the greatest concern in their consideration of recommendations, and the work group expects to review a CDC assessment of laboratory tests for prevaccination screening at a future meeting.

Dr. Esquilin had no financial conflicts to disclose.

SOURCE: Esquilin E. 2020. February meeting of the CDC Advisory Committee on Immunization Practices (ACIP) presentation.

Adults are interested in a dengue vaccine for themselves and their children, and physicians recognize that dengue is a public health problem, according to data from parents and physicians in Puerto Rico. Most doctors, but fewer parents, found the idea of protecting children with Dengue vaccine acceptable.

itsmejust/Thinkstock

Lack of detailed information about the vaccine is the greatest barrier to parents’ consent to vaccination, noted Ines Esquilin, MD, of the University of Puerto Rico, San Juan, in a presentation at the February meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The ACIP dengue vaccines work group reviewed data from 102 physicians in Puerto Rico, 82% of which were pediatricians, regarding potential dengue vaccination. Overall, 98% said they considered dengue a significant public health problem in Puerto Rico, and 73% said they would recommend the dengue vaccine to patients if a laboratory test with acceptable specificity were available. Among the physicians who said they would not recommend the vaccine, the most common reason (71%) was concern about the risks of vaccinating individuals with false-positive tests.

The availability of a test that can be performed in the medical office and avoid repeat visits is a major factor in the feasibility of dengue vaccination, Dr. Esquilin said.

The ACIP dengue vaccines work group also sought public opinion on the acceptability of a generic dengue vaccine through focus group sessions with parents of children aged 9-16 years in Puerto Rico, said Dr. Esquilin.

Approximately one-third of the parents said they were willing to vaccinate their children, one-third were unwilling, and one-third were unsure. The most commonly identified barriers to vaccination included lack of information or inconsistent information about the vaccine, high cost/lack of insurance coverage, time-consuming lab test to confirm infection, side effects, potential for false-positive lab results, and low vaccine effectiveness.

Motivating factors for vaccination included correct information about the vaccine, desire to prevent infection, lab-confirmed positive test, support from public health organizations, the presence of a dengue epidemic, and educational forums.

Based in part on these findings, the ACIP dengue vaccines work group noted that the need for an acceptably specific screening lab test is the greatest concern in their consideration of recommendations, and the work group expects to review a CDC assessment of laboratory tests for prevaccination screening at a future meeting.

Dr. Esquilin had no financial conflicts to disclose.

SOURCE: Esquilin E. 2020. February meeting of the CDC Advisory Committee on Immunization Practices (ACIP) presentation.

Adults are interested in a dengue vaccine for themselves and their children, and physicians recognize that dengue is a public health problem, according to data from parents and physicians in Puerto Rico. Most doctors, but fewer parents, found the idea of protecting children with Dengue vaccine acceptable.

itsmejust/Thinkstock

Lack of detailed information about the vaccine is the greatest barrier to parents’ consent to vaccination, noted Ines Esquilin, MD, of the University of Puerto Rico, San Juan, in a presentation at the February meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The ACIP dengue vaccines work group reviewed data from 102 physicians in Puerto Rico, 82% of which were pediatricians, regarding potential dengue vaccination. Overall, 98% said they considered dengue a significant public health problem in Puerto Rico, and 73% said they would recommend the dengue vaccine to patients if a laboratory test with acceptable specificity were available. Among the physicians who said they would not recommend the vaccine, the most common reason (71%) was concern about the risks of vaccinating individuals with false-positive tests.

The availability of a test that can be performed in the medical office and avoid repeat visits is a major factor in the feasibility of dengue vaccination, Dr. Esquilin said.

The ACIP dengue vaccines work group also sought public opinion on the acceptability of a generic dengue vaccine through focus group sessions with parents of children aged 9-16 years in Puerto Rico, said Dr. Esquilin.

Approximately one-third of the parents said they were willing to vaccinate their children, one-third were unwilling, and one-third were unsure. The most commonly identified barriers to vaccination included lack of information or inconsistent information about the vaccine, high cost/lack of insurance coverage, time-consuming lab test to confirm infection, side effects, potential for false-positive lab results, and low vaccine effectiveness.

Motivating factors for vaccination included correct information about the vaccine, desire to prevent infection, lab-confirmed positive test, support from public health organizations, the presence of a dengue epidemic, and educational forums.

Based in part on these findings, the ACIP dengue vaccines work group noted that the need for an acceptably specific screening lab test is the greatest concern in their consideration of recommendations, and the work group expects to review a CDC assessment of laboratory tests for prevaccination screening at a future meeting.

Dr. Esquilin had no financial conflicts to disclose.

SOURCE: Esquilin E. 2020. February meeting of the CDC Advisory Committee on Immunization Practices (ACIP) presentation.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

The Centers for Disease Control and Prevention and the Wisconsin Department of Health Services confirmed a new case of the 2019 Novel Coronavirus (2019-nCoV) on Feb. 5, 2020, bringing the total number of cases in the United States to 12.* 

Earlier in the day, Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, told reporters that 206 individuals under investigation had tested negative for infection with the novel virus and that tests were pending on another 76 individuals.

The agency also announced during a press briefing call that diagnostic test kits will begin shipping on Feb. 5, less than 24 hours after receiving an emergency use authorization from the Food and Drug Administration. Full information is available in an article published in the Morbidity and Mortality Weekly Report.

The emergency use authorization will allow for broader use of the CDC’s 2019-nCoV Real Time RT-PCR Diagnostic Panel, which to date has been limited for use at CDC laboratories. Under the emergency use authorization, the diagnostic kit is authorized for patients who meed the CDC criteria for 2019-nCoV testing. The diagnostic test is a reverse transcriptase polymerase chain reaction test that provides presumptive detection of 2019-nCoV from respiratory secretions, such as nasal or oral swabs. A positive test indicates likely infection, although a negative test does not preclude infection and should not be the sole determination for patient management decisions.

“Today, the test kits will start shipping to over 100 U.S. public health labs,” she said. “Each of these labs is required to perform international verification for [Clinical Laboratory Improvement Amendments] compliance prior to reporting out. This process is expected to take a few days.”

Dr. Messonnier said that 200 test kits will be distributed to domestic labs and another 200 test kits will go to select international labs. Each kit can perform diagnostics on 700-800 patient samples.

“What that means is that, by the start of next week, we expect there to be much enhanced capacity for laboratory testing closer to our patients,” she said, adding that additional test kits are being produced and will be available for ordering in the future. Each laboratory that places an order will receive one test kit.

“Distribution of these tests will improve the global capacity to detect and respond to this new virus,” Dr. Messonnier said. “Availability of this test is a starting place for greater commercial availability of diagnostic testing for nCoV.”

The CDC also said that the next batch of passengers arriving from Wuhan, China, will be arriving in one of four locations: Travis Air Force Base, Fairfield, Calif.; Marine Corps Air Station Miramar, San Diego; Lackland Air Force Base, San Antonio; and Eppley Airfield, Omaha, Neb. Passengers will be quarantined for up to 14 days from the day the flight left Wuhan and medical care will be provided if needed.

“We do not believe these people pose a threat to the communities where they are being housed as we are taking measures to minimize any contact,” she said, adding that confirmed infections are expected among these and other returning travelers.

Dr. Messonnier warned that the quarantine measures “may not catch every single returning traveler returning with novel coronavirus, given the nature of this virus and how it is spreading. But if we can catch the majority of them, that will slow the entry of this virus into the United States.”

[email protected]

*This story was updated on 02/05/2020. 

The Centers for Disease Control and Prevention and the Wisconsin Department of Health Services confirmed a new case of the 2019 Novel Coronavirus (2019-nCoV) on Feb. 5, 2020, bringing the total number of cases in the United States to 12.* 

Earlier in the day, Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, told reporters that 206 individuals under investigation had tested negative for infection with the novel virus and that tests were pending on another 76 individuals.

The agency also announced during a press briefing call that diagnostic test kits will begin shipping on Feb. 5, less than 24 hours after receiving an emergency use authorization from the Food and Drug Administration. Full information is available in an article published in the Morbidity and Mortality Weekly Report.

The emergency use authorization will allow for broader use of the CDC’s 2019-nCoV Real Time RT-PCR Diagnostic Panel, which to date has been limited for use at CDC laboratories. Under the emergency use authorization, the diagnostic kit is authorized for patients who meed the CDC criteria for 2019-nCoV testing. The diagnostic test is a reverse transcriptase polymerase chain reaction test that provides presumptive detection of 2019-nCoV from respiratory secretions, such as nasal or oral swabs. A positive test indicates likely infection, although a negative test does not preclude infection and should not be the sole determination for patient management decisions.

“Today, the test kits will start shipping to over 100 U.S. public health labs,” she said. “Each of these labs is required to perform international verification for [Clinical Laboratory Improvement Amendments] compliance prior to reporting out. This process is expected to take a few days.”

Dr. Messonnier said that 200 test kits will be distributed to domestic labs and another 200 test kits will go to select international labs. Each kit can perform diagnostics on 700-800 patient samples.

“What that means is that, by the start of next week, we expect there to be much enhanced capacity for laboratory testing closer to our patients,” she said, adding that additional test kits are being produced and will be available for ordering in the future. Each laboratory that places an order will receive one test kit.

“Distribution of these tests will improve the global capacity to detect and respond to this new virus,” Dr. Messonnier said. “Availability of this test is a starting place for greater commercial availability of diagnostic testing for nCoV.”

The CDC also said that the next batch of passengers arriving from Wuhan, China, will be arriving in one of four locations: Travis Air Force Base, Fairfield, Calif.; Marine Corps Air Station Miramar, San Diego; Lackland Air Force Base, San Antonio; and Eppley Airfield, Omaha, Neb. Passengers will be quarantined for up to 14 days from the day the flight left Wuhan and medical care will be provided if needed.

“We do not believe these people pose a threat to the communities where they are being housed as we are taking measures to minimize any contact,” she said, adding that confirmed infections are expected among these and other returning travelers.

Dr. Messonnier warned that the quarantine measures “may not catch every single returning traveler returning with novel coronavirus, given the nature of this virus and how it is spreading. But if we can catch the majority of them, that will slow the entry of this virus into the United States.”

[email protected]

*This story was updated on 02/05/2020. 

The Centers for Disease Control and Prevention and the Wisconsin Department of Health Services confirmed a new case of the 2019 Novel Coronavirus (2019-nCoV) on Feb. 5, 2020, bringing the total number of cases in the United States to 12.* 

Earlier in the day, Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, told reporters that 206 individuals under investigation had tested negative for infection with the novel virus and that tests were pending on another 76 individuals.

The agency also announced during a press briefing call that diagnostic test kits will begin shipping on Feb. 5, less than 24 hours after receiving an emergency use authorization from the Food and Drug Administration. Full information is available in an article published in the Morbidity and Mortality Weekly Report.

The emergency use authorization will allow for broader use of the CDC’s 2019-nCoV Real Time RT-PCR Diagnostic Panel, which to date has been limited for use at CDC laboratories. Under the emergency use authorization, the diagnostic kit is authorized for patients who meed the CDC criteria for 2019-nCoV testing. The diagnostic test is a reverse transcriptase polymerase chain reaction test that provides presumptive detection of 2019-nCoV from respiratory secretions, such as nasal or oral swabs. A positive test indicates likely infection, although a negative test does not preclude infection and should not be the sole determination for patient management decisions.

“Today, the test kits will start shipping to over 100 U.S. public health labs,” she said. “Each of these labs is required to perform international verification for [Clinical Laboratory Improvement Amendments] compliance prior to reporting out. This process is expected to take a few days.”

Dr. Messonnier said that 200 test kits will be distributed to domestic labs and another 200 test kits will go to select international labs. Each kit can perform diagnostics on 700-800 patient samples.

“What that means is that, by the start of next week, we expect there to be much enhanced capacity for laboratory testing closer to our patients,” she said, adding that additional test kits are being produced and will be available for ordering in the future. Each laboratory that places an order will receive one test kit.

“Distribution of these tests will improve the global capacity to detect and respond to this new virus,” Dr. Messonnier said. “Availability of this test is a starting place for greater commercial availability of diagnostic testing for nCoV.”

The CDC also said that the next batch of passengers arriving from Wuhan, China, will be arriving in one of four locations: Travis Air Force Base, Fairfield, Calif.; Marine Corps Air Station Miramar, San Diego; Lackland Air Force Base, San Antonio; and Eppley Airfield, Omaha, Neb. Passengers will be quarantined for up to 14 days from the day the flight left Wuhan and medical care will be provided if needed.

“We do not believe these people pose a threat to the communities where they are being housed as we are taking measures to minimize any contact,” she said, adding that confirmed infections are expected among these and other returning travelers.

Dr. Messonnier warned that the quarantine measures “may not catch every single returning traveler returning with novel coronavirus, given the nature of this virus and how it is spreading. But if we can catch the majority of them, that will slow the entry of this virus into the United States.”

[email protected]

*This story was updated on 02/05/2020. 

Enrichment next-generation sequencing (NGS) provides a more cost-efficient and sensitive method for detecting and sequencing novel coronaviruses from wild bat populations, according to a study reported in mSphere, an open-access journal from the American Society for Microbiology.

Wikimedia Commons/Mickey Samuni-Blank

With the appearance of the new zoonotic Wuhan coronavirus, the importance of monitoring the likelihood of new virus risks in wildlife reservoirs has been heightened. Bats in particular have been found to be the most common reservoir of coronaviruses, including being a probable source or mixing vessel for two previous modern epidemic coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

“We should be alert and vigilant with the knowledge that bat CoVs [coronaviruses] are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to Bei Li, MD, of the Wuhan (China) Institute of Virology, and colleagues.

“We previously provided serological evidence that [HKU8-related] CoV had jumped over from bats to camels and recombined with MERS-CoV, alerting other researchers that the CoV species could be dangerous. ... Genome-level comparison is needed to monitor the risk of alterations in species tropism and pathogenesis,” according to study authors. They performed a study to develop a more effective and cost efficient method for detecting and sequencing novel coronaviruses in the bat population.

The taxonomy of coronaviruses is particularly complex and may be too narrowly defined, given the high level of genetic plasticity found. There are four genera (Alpha-, Beta-, Gamma-, and Deltacoronavirus) consisting of 38 unique species in the CoV subfamily Orthocoronavirinae, and the number is increasing. Viral taxomists rely on the open reading frame 1b (ORF1b) gene for classification, but viruses in the same species may show great diversity in regions outside ORF1b, confounding the species designation. In particular, bat CoVs classed as the same species can differ significantly in terms of receptor usage or virus-host interaction, as observed in bat SARS-related CoVs, according to the researchers.

The researchers obtained RNA from previous bat CoV surveillance projects, which used bat rectal swabs. Libraries for NGS were constructed from total RNA and processed to generate RNA fragments larger than 300 nucleotides. Following first- and second-strand cDNA synthesis, double-stranded cDNA was purified and the library was amplified by polymerase chain reaction (PCR) technology.

Targeted CoV genome enrichment was achieved using 4,303 customized biotinylated 120-mer baits. These baits were designed from 90 representative CoV genomes, and in silico analysis determined that these baits should target the known CoV species tested. These baits were added and hybridized to the libraries. To capture virus-specific library fragments, streptavidin magnetic beads (which bind to biotin) were added to the hybridization reaction mixture. The beads were then washed to remove unbound DNA. The postcapture virus-specific library fragments were then amplified using a subsequent round of PCR.

The enrichment NGS were retrospectively complemented with unbiased NGS and/or additional Sanger sequencing to obtain full-length genomes. The study showed that enrichment NGS not only decreased the amount of data requiring analysis but produced full-length genome coverage in both laboratory and clinical samples.

Using this technology, the researchers “effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.” In addition, they noted that using standard targeted PCR, which is common practice for many surveillance studies, would not have discovered this diversity.

“We should be alert and vigilant with the knowledge that bat CoVs are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to the researchers.

“We have provided a cost-effective methodology for bat CoV surveillance. The high genetic diversity observed in our newly sequenced samples suggests further work is needed to characterize these bat CoVs prior to or in the early stages of spillover to humans,” the authors concluded.

This study was supported by the Chinese government. The authors reported that they had no conflicts.

Viral genome data for new CoVs from this study are available in GenBank under accession numbers MN611517 to MN611525.

[email protected]

SOURCE: Li B et al. mSphere 2020 Jan 29;5:e00807-19.

Enrichment next-generation sequencing (NGS) provides a more cost-efficient and sensitive method for detecting and sequencing novel coronaviruses from wild bat populations, according to a study reported in mSphere, an open-access journal from the American Society for Microbiology.

Wikimedia Commons/Mickey Samuni-Blank

With the appearance of the new zoonotic Wuhan coronavirus, the importance of monitoring the likelihood of new virus risks in wildlife reservoirs has been heightened. Bats in particular have been found to be the most common reservoir of coronaviruses, including being a probable source or mixing vessel for two previous modern epidemic coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

“We should be alert and vigilant with the knowledge that bat CoVs [coronaviruses] are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to Bei Li, MD, of the Wuhan (China) Institute of Virology, and colleagues.

“We previously provided serological evidence that [HKU8-related] CoV had jumped over from bats to camels and recombined with MERS-CoV, alerting other researchers that the CoV species could be dangerous. ... Genome-level comparison is needed to monitor the risk of alterations in species tropism and pathogenesis,” according to study authors. They performed a study to develop a more effective and cost efficient method for detecting and sequencing novel coronaviruses in the bat population.

The taxonomy of coronaviruses is particularly complex and may be too narrowly defined, given the high level of genetic plasticity found. There are four genera (Alpha-, Beta-, Gamma-, and Deltacoronavirus) consisting of 38 unique species in the CoV subfamily Orthocoronavirinae, and the number is increasing. Viral taxomists rely on the open reading frame 1b (ORF1b) gene for classification, but viruses in the same species may show great diversity in regions outside ORF1b, confounding the species designation. In particular, bat CoVs classed as the same species can differ significantly in terms of receptor usage or virus-host interaction, as observed in bat SARS-related CoVs, according to the researchers.

The researchers obtained RNA from previous bat CoV surveillance projects, which used bat rectal swabs. Libraries for NGS were constructed from total RNA and processed to generate RNA fragments larger than 300 nucleotides. Following first- and second-strand cDNA synthesis, double-stranded cDNA was purified and the library was amplified by polymerase chain reaction (PCR) technology.

Targeted CoV genome enrichment was achieved using 4,303 customized biotinylated 120-mer baits. These baits were designed from 90 representative CoV genomes, and in silico analysis determined that these baits should target the known CoV species tested. These baits were added and hybridized to the libraries. To capture virus-specific library fragments, streptavidin magnetic beads (which bind to biotin) were added to the hybridization reaction mixture. The beads were then washed to remove unbound DNA. The postcapture virus-specific library fragments were then amplified using a subsequent round of PCR.

The enrichment NGS were retrospectively complemented with unbiased NGS and/or additional Sanger sequencing to obtain full-length genomes. The study showed that enrichment NGS not only decreased the amount of data requiring analysis but produced full-length genome coverage in both laboratory and clinical samples.

Using this technology, the researchers “effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.” In addition, they noted that using standard targeted PCR, which is common practice for many surveillance studies, would not have discovered this diversity.

“We should be alert and vigilant with the knowledge that bat CoVs are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to the researchers.

“We have provided a cost-effective methodology for bat CoV surveillance. The high genetic diversity observed in our newly sequenced samples suggests further work is needed to characterize these bat CoVs prior to or in the early stages of spillover to humans,” the authors concluded.

This study was supported by the Chinese government. The authors reported that they had no conflicts.

Viral genome data for new CoVs from this study are available in GenBank under accession numbers MN611517 to MN611525.

[email protected]

SOURCE: Li B et al. mSphere 2020 Jan 29;5:e00807-19.

Enrichment next-generation sequencing (NGS) provides a more cost-efficient and sensitive method for detecting and sequencing novel coronaviruses from wild bat populations, according to a study reported in mSphere, an open-access journal from the American Society for Microbiology.

Wikimedia Commons/Mickey Samuni-Blank

With the appearance of the new zoonotic Wuhan coronavirus, the importance of monitoring the likelihood of new virus risks in wildlife reservoirs has been heightened. Bats in particular have been found to be the most common reservoir of coronaviruses, including being a probable source or mixing vessel for two previous modern epidemic coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

“We should be alert and vigilant with the knowledge that bat CoVs [coronaviruses] are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to Bei Li, MD, of the Wuhan (China) Institute of Virology, and colleagues.

“We previously provided serological evidence that [HKU8-related] CoV had jumped over from bats to camels and recombined with MERS-CoV, alerting other researchers that the CoV species could be dangerous. ... Genome-level comparison is needed to monitor the risk of alterations in species tropism and pathogenesis,” according to study authors. They performed a study to develop a more effective and cost efficient method for detecting and sequencing novel coronaviruses in the bat population.

The taxonomy of coronaviruses is particularly complex and may be too narrowly defined, given the high level of genetic plasticity found. There are four genera (Alpha-, Beta-, Gamma-, and Deltacoronavirus) consisting of 38 unique species in the CoV subfamily Orthocoronavirinae, and the number is increasing. Viral taxomists rely on the open reading frame 1b (ORF1b) gene for classification, but viruses in the same species may show great diversity in regions outside ORF1b, confounding the species designation. In particular, bat CoVs classed as the same species can differ significantly in terms of receptor usage or virus-host interaction, as observed in bat SARS-related CoVs, according to the researchers.

The researchers obtained RNA from previous bat CoV surveillance projects, which used bat rectal swabs. Libraries for NGS were constructed from total RNA and processed to generate RNA fragments larger than 300 nucleotides. Following first- and second-strand cDNA synthesis, double-stranded cDNA was purified and the library was amplified by polymerase chain reaction (PCR) technology.

Targeted CoV genome enrichment was achieved using 4,303 customized biotinylated 120-mer baits. These baits were designed from 90 representative CoV genomes, and in silico analysis determined that these baits should target the known CoV species tested. These baits were added and hybridized to the libraries. To capture virus-specific library fragments, streptavidin magnetic beads (which bind to biotin) were added to the hybridization reaction mixture. The beads were then washed to remove unbound DNA. The postcapture virus-specific library fragments were then amplified using a subsequent round of PCR.

The enrichment NGS were retrospectively complemented with unbiased NGS and/or additional Sanger sequencing to obtain full-length genomes. The study showed that enrichment NGS not only decreased the amount of data requiring analysis but produced full-length genome coverage in both laboratory and clinical samples.

Using this technology, the researchers “effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.” In addition, they noted that using standard targeted PCR, which is common practice for many surveillance studies, would not have discovered this diversity.

“We should be alert and vigilant with the knowledge that bat CoVs are likely to cause another disease outbreak, not only because of their prevalence but also because the high frequency of recombination between viruses may lead to the generation of viruses with changes in virulence,” according to the researchers.

“We have provided a cost-effective methodology for bat CoV surveillance. The high genetic diversity observed in our newly sequenced samples suggests further work is needed to characterize these bat CoVs prior to or in the early stages of spillover to humans,” the authors concluded.

This study was supported by the Chinese government. The authors reported that they had no conflicts.

Viral genome data for new CoVs from this study are available in GenBank under accession numbers MN611517 to MN611525.

[email protected]

SOURCE: Li B et al. mSphere 2020 Jan 29;5:e00807-19.