The World Health Organization (WHO) said in a new risk assessment today that two recent human H5N1 avian flu cases involved the older 2.3.2.1c clade, not the one circulating widely in poultry in multiple world regions.

The two cases were reported in January and are part of an uptick in human H5N1 infections in Cambodia, following a nearly decade-long absence. The WHO also added new details about the infections and investigations. One of the cases was found as part of severe acute respiratory illness surveillance, and the other was identified by a doctor at a site that wasn't in a surveillance network.

Exposure to sick birds preceded both infections

Both patients had been exposed to sick birds before their symptoms began. Backyard chickens were found dead around the 3-year-old child's house, and the 69-year-old patient had raised domestic birds and fighting roosters, of which three chickens were positive for H5N1.

Monitoring and testing of the two patients' contacts yielded no other flu cases, except for an unrelated influenza B infection in one of the older patient's contacts.

Risk remains where poultry are infected

The two new cases put the number of H5N1 in Cambodia at 8 since 2023. Since the first infections were reported in 2003, the country has reported 64 cases, 41 of them fatal. The WHO said the risk to the general human population from H5N1 viruses remains low and that sporadic human infections will likely continue, especially in rural Cambodia and other countries where the virus is endemic in poultry.

The agency urged people to avoid high-risk environments such as live-animal markets and to quickly report unexpected animal deaths to veterinary officials. In countries where avian flu is known to circulate, the WHO recommends wearing respiratory protection and barriers while slaughtering or handling slaughtered poultry.

The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) announced today that it will award biotechnology company Visby Medical of San Jose, California, up to $1.8 million to develop a portable polymerase chain reaction (PCR) test that can detect gonorrhea and assess its susceptibility to ciprofloxacin.

Although ciprofloxacin is no longer a recommended first-line antibiotic for infections caused by Neisseria gonorrhoeae because of resistance, some strains of the bacterium remain susceptible to the oral antibiotic. Knowing which infections are susceptible to ciprofloxacin at the point of care could enable clinicians to reserve ceftriaxone, which is the last remaining antibiotic that remains widely effective against N gonorrhoeae.

Gonorrhea is among the sexually transmitted infections (STIs) that have been consistently climbing in the United States and other parts of the world over the past several years, and is the second most common bacterial STI. In 2020, roughly 82 million people worldwide reported gonorrhea infections.

Need for rapid, accurate tests

"The sexually transmitted infections epidemic continues to increase," Gary Schoolnik, MD, chief medical officer of Visby Medical, said in a CARB-X press release. "That is why healthcare providers in [emergency departments], urgent care clinics, community health centers and physicians' offices need accurate and rapid diagnostic tests to enable same-visit, data-driven treatment based on a test result that identifies the pathogen and its antibiotic susceptibility."

CARB-X research and development chief Erin Duffy, PhD, said the PCR test should be "rapidly and highly deployable" in low-resource settings.

"Additionally, for regions where ciprofloxacin remains a viable treatment, the Visby Medical diagnostic gives confidence that the physician is making the correct treatment decision," she said.

The funding will also support development of a test for Chlamydia trachomitis and Trichomonas vaginalis in men based on urine samples.

The test is the fourth project, and the first diagnostic, to receive funding from CARB-X's 2022-23 funding call. Since its launch in 2016, CARB-X has supported 95 research and development projects in 13 countries.

If the US Food and Drug Administration (FDA) pulls cough and cold medications containing the active ingredient phenylephrine from shelves, it will set off a wave of drug supply chain problems, researchers from the University of Pittsburgh and the University of Toronto assert today in JAMA.

In September 2023, the FDA's Non-prescription Drug Advisory Committee reviewed new data on phenylephrine, concluding that it is ineffective. The committee recommended that the drug, used in many over-the-counter nasal decongestants as a single ingredient or in combination with other ingredients, be removed from the market.

For today's study, the researchers analyzed pharmacy and retail-outlet purchases of phenylephrine and pseudoephedrine—the only two nasal decongestants approved by the FDA—from 2012 through 2021 using IQVIA's Multinational Integrated Data Analysis quarterly sales-volume data.

Few multi-symptom alternatives available

During the study period, 732 unique phenylephrine medications (21 stand-alone, 711 combination products) and 495 pseudoephedrine preparations (54 stand-alone, 441 combination) were on the market.

US pharmacies bought 19.8 billion units of phenylephrine products for $3.4 billion and 13.2 billion units of pseudoephedrine preparations for $3.8 billion. Phenylephrine sales declined significantly over time, from 1.68 billion units in 2012 to 0.98 billion units in 2021.

A comparable pathway is needed for drugs that are sold over the counter as exists for post-approval monitoring of the risks and efficacy of prescription drugs.

The researchers said that if the FDA decides to pull phenylephrine, most multi-symptom products will be unavailable as they undergo reformulation, as few pseudoephedrine alternatives are available. The FDA is requesting public comment before taking any action. In the event of an administrative removal of these products, the authors said clinicians and consumers could substitute oral pseudoephedrine or intranasal decongestants such as phenylephrine or oxymetazoline.

"The FDA needs to hold over-the-counter drugs to a standard of effectiveness similar to that of prescription drugs," Timothy Anderson, MD, assistant professor of medicine at the University of Pittsburgh, said in a university news release. "A comparable pathway is needed for drugs that are sold over the counter as exists for post-approval monitoring of the risks and efficacy of prescription drugs. This will require a substantial investment in infrastructure to expand capacity."

Though respiratory syncytial virus (RSV) is the most common pathogen associated with infant hospitalization and ventilation worldwide, infections with human rhinovirus (HRV) also make up a significant proportion of hospitalizations for viral bronchiolitis—up to two-thirds that of RSV-related hospital admissions, according to a new research letter in JAMA Network Open.

With recent developments with monoclonal antibodies and maternal vaccines, the landscape of infant hospitalizations due to RSV may soon change, the authors write, with RSV-related hospitalizations reduced by more than 80%. Less understood is the role HRV plays in infant hospitalizations.

To assess the burden of HRV, the authors looked at a historical cohort of infants hospitalized in a tertiary hospital in Lyon, France, with laboratory-confirmed RSV or HRV infections between 2019 and 2022.

From July 1, 2019, to June 30, 2022, a total of 1,122 RSV and 766 HRV infections were identified, meaning the admission rate due to HRV was 68% of the total for RSV. The hospitalization ratio of HRV to RSV days was 51% (3,608 of 7,017 infant-days), and for days of ventilation, 27% (392 of 1,426 infant-days).

The temporal distribution showed that HRV-related burden was spread across the year, while RSV-related burden was seasonal.

"The temporal distribution showed that HRV-related burden was spread across the year, while RSV-related burden was seasonal," the authors said.

"To protect hospital and nonhospital pediatric settings from the devastating effects of multipathogen winter epidemics, efforts must be made to include HRV in the development of multipathogen vaccines and to continue to optimize patient management by developing tailored protocols for home enteral nutrition and home oxygen therapy for infants with moderately severe bronchiolitis," they concluded.

• Amid a rising threat of vector-borne illnesses due to multiple factors, the US Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC) this week published a national strategy to prevent and control the diseases in humans. The strategy was developed by a working group with contributions from 17 federal agencies, HHS said in a press release. Development of the strategy was directed by the 2019 Kay Hagan Tick Act—named after the US Senator who died of complications from a tick-borne illness. Along with identifying challenges and opportunities for improving control of vector-borne threats, the plan details an approach for developing new diagnostics, drugs, and treatments. The CDC has said vector-borne illnesses cases—caused by biting insects like mosquitoes and arachnids like ticks— have doubled in the past two decades because of shifting land-use patterns, increased global travel and trade, and climate change. It has also documented a geographic expansion of the vectors and a growing number of pathogens spread by vectors. "Yet only one vaccine is available to protect people against almost 20 domestic threats," HHS said.
• The World Health Organization (WHO) today announced that Uruguay has informed it of a human Western equine encephalitis (WEE) case, its first in than more than a decade. The detection follows recent cases in Argentina, which in December confirmed its first infection in more than 20 years. Both countries have reported several outbreaks in horses, which can also contract the disease from mosquitoes that carry the virus. Uruguay's case involves a 42-year-old man from a rural part of San Jose department in the south. His symptoms began in early January. He was hospitalized in intensive care for a few days but has since recovered. Investigators found that he lives in an area with known WEE circulation and the country's highest incidence of cases in horses, though he did not have contact with the animals. Uruguay has reported a rise in equine WEE outbreaks since November 2023.
• Brazilian health officials have notified the WHO about a variant H1N1 (H1N1v) swine flu case in a man from Toledo in Parana state. According to a WHO notification, the man has underlying medical conditions. He was hospitalized on December 16, 2023. He had no contact with pigs or sick people, and investigators found no other related illnesses among his contacts. The WHO said the case is likely sporadic and poses a low risk of community spread. Genetic analysis found that the virus from the man's sample is very similar to H1N1v viruses from recent human cases in Parana state in recent years, which the WHO said might signal ongoing spread in animals. Brazil has reported sporadic cases involving variant flu strains, but with no evidence of sustained human-to-human transmission. The virus has been sent to the CDC for further assessment.