Alarm Bells Ring as Bird Flu Shows Signs of Human Transmission

Alarm Bells Ring as Bird Flu Shows Signs of Human Transmission

United States: The recent avian influenza incursion into dairy herds has, as documented by public health authorities, extended to merely three agricultural laborers in the United States. These individuals experienced predominantly mild manifestations.

Nonetheless, this does not assure that the H5N1 virus will persist in its current benign form should it commence interhuman transmission. Accruing data from the animal kingdom and global reports suggest otherwise.

Certain dairy bovines succumbed to H5N1, either perishing or necessitating culling. Infected terns exhibited disorientation and impaired flight capabilities. Young elephant seals experienced respiratory distress and tremors post-infection. Felines, having contracted the virus, lost their sight and ambulated in circles, with a mortality rate of two-thirds.

“I unequivocally believe there is no room for complacency,” stated Anice Lowen, a virologist at Emory University, according to the reports by The New York Times.

“H5N1 is a highly virulent influenza virus, warranting significant concern if it begins to infect humans,” she further emphasized.

Experimental inoculation of ferrets via ocular pathways—the hypothesized infection route in the US farmworkers—revealed rapid viral dissemination to their respiratory tracts, pulmonary systems, gastrointestinal tracts, and cerebral regions, according to a Wednesday report.

Other research indicated analogous patterns in mice ingesting tainted milk. These findings imply that entry through ocular or digestive systems does not diminish the virus’s potential threat.

H5N1 has demonstrated a proclivity for host diversity, rapidly infecting wild avians, poultry, rodents, ursines, felines, and pinnipeds. Since its 1996 emergence in Hong Kong, it has also afflicted nearly 900 humans.

An older Asian strain has resulted in a 50% mortality rate among those infected.

Among the 15 confirmed human cases of the current strain infecting cattle, one individual in China perished, and another required hospitalization. Two patients in Chile and Ecuador exhibited severe symptoms. The four American cases—one last year and three from the current outbreak—were comparatively less severe.

Crucially, no avian influenza strain has demonstrated efficient human-to-human transmission. This does not preclude H5N1 from acquiring such capability, warned Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison.

“I believe the virus is evidently altering its properties, given the unprecedented cattle outbreaks,” Dr Kawaoka observed. Conjunctivitis, or pink eye, a primary symptom in two of the three farmworkers, is atypical for H5N1. The virus’s presence in the mammary glands of bovines and non-lactating mice was equally unexpected, as per The New York Times.

The paramount concern is that H5N1, as it continues infecting mammals and evolving, might develop the mutations required for efficient human transmission, potentially triggering another pandemic.

Influenza’s incubation period spans two to four days, and a human-adapted strain could propagate widely before detection, cautioned Erin Sorrell, a virologist and senior scholar at the Johns Hopkins Center for Health Security.

“If it penetrates the general populace, it’s too late,” she asserted. “The opportunity will have been missed.”

Influenza typically exerts its harshest impact on elderly individuals and children under five. (The 2009 swine flu outbreak, though less catastrophic than anticipated, claimed nearly 1,300 children.) The severity of illness hinges on viral load, exposure duration, infection route, and the individual’s genetic predisposition and general health.

Infected persons generally present with fever and respiratory symptoms; some progress rapidly to pneumonia or death. Should the avian influenza virus adapt to humans, a global need for billions of vaccine and antiviral doses would ensue to mitigate these outcomes.

The federal stockpile includes four types of influenza antivirals, but their efficacy is contingent on administration within 48 hours of symptom onset. A recent review found insufficient evidence to evaluate the effectiveness of three of the four drugs, including the widely used oseltamivir (Tamiflu), as reported by The New York Times.

Some emergent H5N1 variants possess mutations conferring resistance to oseltamivir and the other two drugs; though fortunately, these changes have not proliferated extensively among animal populations. No resistance mutations have been observed against the fourth drug, baloxavir.

However, the stockpile holds only a few hundred thousand doses of baloxavir, according to David Boucher, infectious disease director at the federal Administration for Strategic Preparedness and Response.

Vaccines are a more reliable measure to curb a pandemic, yet adequate doses would not be available for many months at minimum. Even if global seasonal flu vaccine production were entirely redirected to H5N1 vaccines, the output would suffice for fewer than two billion people, assuming each person required two doses.

In the United States, the national stockpile contains hundreds of thousands of vaccine doses ready for deployment to at-risk groups, including children. Government-contracted companies could produce over 100 million doses within the first 130 days, Dr. Boucher stated.

Officials recently announced measures to prepare 4.8 million doses for bottling without disrupting seasonal flu vaccine production.

Nonetheless, these plans hinge on the virus’s behavior, as per the New York Times.

Since H5N1’s initial detection, it has diversified into numerous forms, prompting scientists to compile a library of 40 candidate vaccine viruses. This preparedness saves crucial time, as creating a new candidate virus can take three months, noted Todd Davis, a virologist at the Centers for Disease Control and Prevention.

To date, he added, the virus has undergone minimal changes, particularly in the segment that binds to human cells, known as hemagglutinin or HA.

For H5N1 to transmit among humans, it would need significant alterations, some experts contended. “If this virus jumps to humans, expect HA to mutate, as the current HA does not efficiently bind to human cells,” said Scott Hensley, an immunologist at the University of Pennsylvania.

Traditional flu vaccines are developed by cultivating candidate viruses in eggs or mammalian cells, processes rife with potential complications: the virus may grow too slowly or mutate excessively during cultivation.

In 2009, the candidate virus grew well in eggs but evolved into a poor match for the wild H1N1 virus, causing substantial delays in public distribution. “By the time vaccine stocks were available, the initial pandemic wave had subsided,” Dr Hensley recounted.

CSL Sequiris, a premier seasonal flu vaccine producer, possesses an FDA-approved cell-based H5N1 vaccine.

In a pandemic scenario, once CSL receives a matching candidate vaccine virus, it could produce 150 million doses for Americans within six months, stated Marc Lacey, an executive director at the company. (The company also maintains contracts with 19 other nations.)

Yet, 150 million doses would suffice for merely one-fifth of the American populace. Federal officials are also exploring mRNA avian influenza vaccines, which, as demonstrated by the Covid pandemic, can be produced swiftly to protect both bovines and humans. Dr Hensley’s team is currently testing an mRNA vaccine in cattle.

Experts indicated that officials have been hesitant to deploy vaccines for cattle due to trade implications: some countries prohibit imports from vaccinated livestock.

However, immunizing cattle would reduce the risk to agricultural workers and other bovines, curtailing the virus’s spread and evolutionary opportunities.

Federal authorities have also been reluctant to vaccinate farmworkers, citing the currently low risk.

The gravest peril, Dr Lowen of Emory pointed out, is if a farmworker contracts both H5N1 and a seasonal influenza virus. Flu viruses are adept at gene exchange, and a co-infection would grant H5N1 the potential to acquire genes facilitating efficient human transmission akin to seasonal flu.

This risk underscores the imperative of vaccinating farmworkers; Dr Lowen asserted, “Mitigating seasonal infection in individuals exposed to H5N1 could substantially diminish risk.”

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