A dramatic increase in whooping cough cases has been observed in the United States, with the current figures being a staggering fivefold increase compared to the same period in the previous year. According to the US Centers for Disease Control and Prevention (CDC), this represents the highest incidence of pertussis infections since 2014, and there are no signs of the trend reversing. Dr. Susan Hariri from the CDC's National Center for Immunization and Respiratory Diseases presented these alarming statistics at a recent expert meeting focused on advising the US Food and Drug Administration (FDA) on vaccine-related decisions.

Prior to the Covid-19 pandemic, there was already a noticeable upward trend in whooping cough cases within the US. This was attributed to the fact that the existing vaccines provide robust initial protection that diminishes after a couple of years. Dr. Archana Chatterjee, a pediatric disease specialist and dean of the Chicago Medical School, highlighted at the meeting that "our current pertussis vaccines have served us well for decades, but their efficacy is not as robust as it once was."

The committee convened on Friday to deliberate on the potential authorization for pharmaceutical companies to conduct human challenge trials, a method of testing vaccines by intentionally exposing participants to whooping cough. During the pandemic, cases of whooping cough, like many other infectious diseases, plummeted due to reduced social interactions and increased preventative measures against Covid-19. In 2020, the US reported approximately 6,000 cases of pertussis, which further decreased to around 2,000 cases in 2021. The numbers were approximately 3,000 cases in 2022 and about 5,000 the year prior. In contrast, this year has seen a significant rise with 14,569 cases reported, compared to 2,844 during the same period last year, as per the CDC’s Nationally Notifiable Diseases Surveillance System.

Whooping cough initially presents symptoms that are indistinguishable from a common cold: a runny nose, sneezing, mild fever, and an irritating cough. After a week or two, the infection progresses to a more severe stage, characterized by intense, full-body coughing fits. These episodes can be so extreme that they lead to vomiting or even broken ribs, often accompanied by a distinctive whooping sound as the individual gasps for air. Antibiotics can effectively treat the infection if caught early, before the onset of the exhausting and painful cough. Beyond this point, the only recourse is symptomatic relief with ample rest and hydration while the infection runs its course. Unvaccinated infants and adults are at the highest risk of severe infection and, in rare cases, death. However, there has been a growing trend of vaccinated individuals also contracting the infection.

Typically, young children receive a series of five vaccinations against pertussis—known as DTaP or TdaP, which also guard against tetanus and diphtheria—by the age of 6. Booster shots are recommended for children aged 11 or 12, and pregnant women are advised to receive the vaccine to protect their newborns. Adults are also encouraged to get boosters every decade. Despite high vaccination rates in the US—approximately 90%— the surge in infections continues, and the reasons behind this are not entirely understood.

There is evidence to suggest that the rise in cases may be due to mutations in the bacteria causing the infection, as explained by Dr. Tod Merkel, associate director of research in the FDA’s Office of Vaccines Research and Review. In the 1990s, the US transitioned from a whole-cell vaccine that often caused fevers and other concerning symptoms post-vaccination to a newer vaccine that was less reactive but also offered less enduring protection. Other countries that adopted the newer vaccines have also witnessed an increase in cases. The diminished protection from the newer vaccines is believed to have allowed the infection to persist and has prompted the bacteria to mutate to evade the immune response triggered by vaccination.

Dr. Merkel reported that 90% of bacterial strains cultured from human infections in the United States are now associated with these vaccine-evasive mutations. For young children vaccinated against pertussis, the protection provided by the vaccine fades rapidly, sometimes within two to three years—well before the recommended age of 11 for a booster shot. Although infants are most vulnerable to severe disease, there has been a notable increase in infections among older children and teenagers as their immunity wanes. This has spurred the search for more effective and longer-lasting vaccines against whooping cough that also minimize side effects.

The development and testing of new vaccines have been challenging due to the cyclical nature of whooping cough outbreaks, which occur every three to five years, and the unpredictability of their occurrence. Manufacturers require a significant number of infected individuals to test their vaccines effectively. This is where human challenge studies come into play.

In some respects, whooping cough is an ideal candidate for human challenge models. The infection is treatable with antibiotics in its early stages, safeguarding study participants from harm. However, most individuals experience mild symptoms during these early stages. Researchers can assess the vaccine's ability to prevent mild initial symptoms and its efficacy in preventing the bacteria from colonizing the nasal passages. However, the pertussis challenge models do not allow for a direct measurement of how well a vaccine might prevent severe disease, which is the primary objective of most vaccines. Additionally, researchers are yet to identify the immune factors that indicate protection from whooping cough, preventing them from gauging whether the protection provided is at least as effective as that of the approved vaccines—a strategy known as bridging.

On Friday, laboratories from Canada and the UK presented their proposed models for conducting challenge trials for pertussis. The FDA advisors were then tasked with evaluating whether these trials could accurately measure the necessary outcomes and, if so, whether they would provide sufficient evidence to support vaccine approval. The models proposed by the labs received mixed feedback from the experts. While some expressed excitement about the potential for accelerated vaccine testing, others questioned whether the studies had been refined enough.

Dr. Melinda Wharton, associate director for vaccine policy and clinical partnerships at the CDC’s National Center for Immunization and Respiratory Diseases, stated, "I am very supportive of this approach; however, I am not entirely certain if we have reached the optimal level of refinement yet."