Global incidence and mortality from invasive fungal disease is substantially higher than previously thought, according to a systematic review published last week in The Lancet Infectious Diseases.

Using data from literature published from 2010 through 2023, along with 85 papers on individual country and global disease burden, the review estimates that over 6.55 million people annually are affected by invasive fungal infection, including over 2.1 million with invasive aspergillosis, 1.8 million with chronic pulmonary aspergillosis, and 1.5 million with a Candida bloodstream infection or invasive candidiasis, 500,000 with Pneumocystis pneumonia, and 194,000 with Cryptococcal meningitis. These infections lead to more than 3.75 million deaths annually, of which 2.55 million are directly attributable to the fungal disease.

The review also estimates that fungal asthma affects approximately 11.5. million people annually, with 92,000 asthma deaths linked to fungal allergy and 46,000 directly attributable.

Higher than previous estimates

The mortality figures are higher than the prior estimates of 1.5 million to 2 million annual deaths, in part because many fungal infections exacerbate diseases such as leukemia, lung cancer, and AIDS, and deaths have often been attributed to those diseases. In addition, many fungal diseases go undiagnosed and untreated because of limited access to diagnostics.

But the new estimates, based on a combination of untreated mortality, the proportion of patients who are treated, and percentage survival in treated patients, suggest that invasive aspergillosis could be responsible for up to one-third of the 3.23 million annual deaths from chronic obstructive pulmonary disease, while 340,000 (28%) of the more than 1.2 million deaths from tuberculosis may have been attributable to chronic pulmonary aspergillosis.

David Denning, PhD, author of the study and a professor at the University of Manchester, says that while the estimates are "necessarily crude" and limited by the scarcity of adequate epidemiologic data from many countries and uncertainty in the mortality rate of undiagnosed and untreated patients, they're "critical to health system capacity building."

"Improved clinical awareness, appropriate sampling, and timely laboratory diagnostic testing, combined with imaging, could definitively reduce the substantial number of mostly avoidable premature deaths from life-threatening fungal disease," he wrote.

CARB-X announced today that it is awarding Dutch contract development and manufacturing organization Intravacc $633,000 to develop a vaccine for gonorrhea.

The money will help support early-stage development of Intravacc's meningococcal outer membrane vesical (OMV) vaccine, which carries tailored gonococcal antigens designed to prevent infections caused by the Neisseria gonorrhoeae bacterium.

Gonorrhea is the world's second most reported sexually transmitted infection, infecting roughly 82 million adults each year. Because of N gonorrhoeae's ability to quickly develop resistance to antibiotics, there is only one antibiotic (ceftriaxone) that remains effective for treating gonorrhea infections. But resistance to ceftriaxone is rising.

"Drug-resistant strains of Neisseria gonorrhoeae have evaded all but one existing antibiotic (ceftriaxone)," Erin Duffy, PhD, R&D Chief of CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), said in a press release. "With an appropriate vaccination strategy, Intravacc's vaccine project, if successful, could prevent the disease, and significantly curb the spread of resistant bacteria across the globe."

The vaccine candidate is the second project to receive a grant through CARB-X's 2022-2023 funding call, and the 93^rd project CARB-X has funded since 2016.

"This CARB-X project allows us to combine our science and OMV expertise for the development of a vaccine for gonorrhea infections," said Intravacc CEO Jan Groen, PhD. "We believe the outcome of this vaccine project could be an important contribution to the antimicrobial resistance epidemic."

A 59-year-old woman from China's Sichuan province is hospitalized in serious condition with H5N6 avian flu, Hong Kong's Centre for Health Protection said today.

The woman is from Ziyang City, her symptoms began on November 25, and she was hospitalized 4 days later. An investigation revealed that she had visited a live-poultry market before her symptoms began.

Her illness marks China's eighth human H5N6 infection of 2023 and the country's 89th since the virus was first detected in humans in 2014. China reported its last H5N6 case in the middle of December, which also involved a woman from Sichuan province. That patient, who died from her infection, had also visited a live-poultry market before she became ill.

Highly pathogenic H5N6 avian flu is known to circulate in poultry in some Asian countries, but only China and Laos have reported human cases, which are often severe or fatal. Most patients have had contact with poultry or had been exposed to poultry environments.

A new study from the US Department of Agriculture shows that elk experimentally infected with SARS-CoV-2 did not shed infectious virus but mounted low-level serologic responses, while mule deer shed and transmitted virus and mounted a more pronounced serologic response to the virus.

The authors of the study, published in Emerging Infectious Diseases, said the results suggest mule deer could spread COVID-19.

"Surveillance studies have demonstrated SARS-CoV-2 infection in free-ranging and captive white-tailed deer in the United States and Canada," the authors wrote explaining previously documented human-to-animal spillovers in cervid populations. "After their displacement in humans, the Alpha and Delta variants of concern persisted in white-tailed deer population."

Surveillance studies have demonstrated SARS-CoV-2 infection in free-ranging and captive white-tailed deer in the United States and Canada.

The experiment consisted of infecting 6 weanling elk (all female) and 6 yearling mule deer (5 female, 1 male), with the Delta variant of SARS-CoV-2. The virus was not detectable from the oral and nasal swabs of elk, but was seen in samples from the mule deer.

"Our results indicate that although elk seem to be minimally susceptible to infection with the Delta variant, mule deer are highly susceptible and capable of transmitting the virus," the authors said. "Inoculated elk showed no clinical signs, did not shed infectious virus, and mounted low-level humoral titers."

There is currently no evidence that wild cervids are a notable source of SARS-CoV-2 exposure for humans, the authors wrote. But the experiment suggests that virus could become established in mule deer as a host species, furthering the rise of novel variants.

Amid rising syphilis infections in the United States and a continuing shortage of Pfizer’s penicillin G injectable Bicillin, the Food and Drug Administration (FDA) is allowing the temporary import of a similar but US-unapproved drug from a French pharmaceutical firm.

In a letter to Paris-based Laboratoires Delbert on the FDA website, the agency approved the import into the US market of prescription penicillin G benzathine (brand name, Extencilline) powder and diluent for reconstitution for injection. The drug is made in Italy and is being imported by Provepharm for distribution by Direct Success.

Key differences between 2 drugs

The FDA letter warns of important differences between Bicillin and Extencilline, such as that the latter lacks some US-required labeling and instructions and contains soy, which may cause allergic reactions in people with a sensitivity. Also, Bicillin comes in filled syringes, while Extencilline requires reconstitution.

The FDA first announced the Bicillin shortage on its website in late April 2023. In June, Pfizer warned customers of a coming depletion. In December, the American Society of Health-System Pharmacists (ASHP) said Bicillin was in short supply because Pfizer, the sole US supplier of the formulation, was prioritizing it for rising adult syphilis cases. "Once current supplies of the pediatric Bicillin-LA vials are depleted, it is unclear when more product will be manufactured," ASHP said on its website.

Since bottoming out in 2000 and 2001, syphilis rates have climbed nearly every year, spiking 28.6% in 2020 and 2021, according to the most recent data from the US Centers for Disease Control and Prevention.

Once current supplies of the pediatric Bicillin-LA vials are depleted, it is unclear when more product will be manufactured.

Rates of the sexually transmitted infection have also been spiking in newborns, with 10 times as many babies born with it in 2022 than the annual rate 10 years prior, raising rates to their highest in 30 years or more, the American Academy of Pediatrics noted on its website. Other antibiotics can be used in adults and children, but they don't offer the convenience of Bicillin, which is the only one approved for treatment of infected pregnant women.