The rapid increase in pertussis cases from the end of 2023 to early 2024 may be due to a variety of reasons. These include periodic outbreaks of pertussis worldwide, an under-identification of pertussis cases in the past, improved diagnostic modalities and access, waning of immunity after immunization with the acellular vaccines, and an accumulated susceptible population.

Experiencing a periodic outbreak of pertussis

Numerous contagious diseases exhibit periodic outbreaks, and the emergence of pertussis in developed countries serves as a typical example. From 2006 to 2016, the national incidence of pertussis remained at a remarkably low level due to the low long-term natural infection rate among the population, creating favorable conditions for an outbreak of this disease. Since 2017, there has been a gradual increase in the incidence of pertussis, placing China currently within a period of periodic epidemic for this disease.

Improved diagnostic modalities and access

The updated 2023 Pertussis Diagnosis and Treatment Guideline in China has expanded the diagnostic criteria to include positive PCR detection of respiratory samples for pertussis. The use of B. pertussis pathogen molecular tests in medical institutions and enhanced awareness of pertussis from doctors may have greatly increased the number of reported pertussis cases in China [13]. Before 2020, diagnosis of pertussis relied on bacterial culture and blood antibody detection. However, culture for B. pertussis requires a well-facilitated laboratory, limiting diagnostic accessibility. Antibody testing also requires multiple blood sampling during different stages of the disease onset, making it difficult to apply in clinical practice. The use of PCR for B. pertussis detection was introduced in the past four years in China, with the first pertussis-specific nucleic acid fluorescence quantitative PCR test kit being authorized in September 2020 [14]. Molecular diagnostic techniques are now used in many children’s hospitals in China, enabling a rapid diagnosis of pertussis in children and adolescents. However, diagnosis of pertussis is still not accessible in most general hospitals for adults. Therefore, a higher number of pediatric pertussis cases were reported by children's hospitals in large cities or provinces. Regional disparities still exist in the reported incidence of pertussis due to different diagnostic tests accessible levels. This aligns with the global distribution of pertussis cases being more prevalent in developed countries and regions like European countries and the United States, as opposed to relatively underdeveloped regions such as Africa, South America, and Asia [15]. Furthermore, the increased public awareness of the disease and patients' heightened willingness to seek medical attention and undergo pertussis testing may also serve as factors contributing to the rise in reported pertussis cases.

Waning of immunity after immunization with acellular vaccines

The duration of this protection for natural immunity varies from 4 to 20 years [2], whereas vaccination-derived antibodies last even less [16]. In China, children are vaccinated with a combination vaccine including diphtheria, tetanus, and acellular pertussis trivalent vaccine (DTaP), the Hib-DTaP quadrivalent vaccine, and the Hib-Polio-DTaP pentavalent vaccine. The waning of immunity has been reported for these vaccines independent of the numbers and concentrations of antigens [2].

The current immunization program in China involves three doses at the ages of three, four, and five months, followed by a booster dose at 18 months. Pertussis vaccination coverage has been reported to be above 95% for many years [17]. However, from a population-level perspective, protective antibodies to pertussis are low or disappear in older children and adolescents. A sero-survey of human pertussis antibody levels in Zhejiang Province indicated that the positive rate of anti-pertussis toxin antibody (anti-PT) in individuals over 5 years old is less than 20% in 2020 [18]. Therefore, the current pertussis vaccination strategy in China does not provide complete protection for school-aged children, adolescents, and adults. Without the establishment of effective population immunity, it becomes challenging to contain the spread of the epidemic.

Accumulation of more susceptible populations

A notable rise in the number of reported cases of pertussis was found from 2017 to 2019 in China; however, this increasing trend was temporarily stopped due to the impact of strict non-pharmaceutical interventions during the COVID-19 pandemic. Consequently, susceptible individuals may have accumulated from 2020 to 2022 due to the epidemic control measures.

Many atypical cases became the potential sources of infection

Pertussis is highly contagious, with a distinct pattern of outbreaks within families. Family members or caregivers, especially mothers, may become sources of infection for infants who are not vaccinated or not completely vaccinated [19]. Adults infected with pertussis often experience milder symptoms and rarely seek medical attention or are seldom suspected of having the disease when seeking care [20]. Pertussis, with a basic reproduction number (R0) of 12–17, mainly spreads through droplets, and the infected person can remain contagious for 1–2 months or even longer [21]. Due to the prolonged period with a low incidence of pertussis, many healthcare workers, especially those in general hospitals, have low awareness of pertussis and cannot provide diagnostic tests timely. Consequently, undiagnosed and untreated cases become sources of infection in the transmission chain of the disease [6].

Variation in B. pertussis strains

Current strains of pertussis in China exhibit a high rate of resistance to macrolide antibiotics, with a resistance rate ranging from 36.7% up to 90% [22,23,24]. This resistance rate is significantly higher than that in Europe and the United States, where macrolide-resistant B. pertussis strains are rare [25]. Without timely and effective antibiotic treatment, the infectivity of pertussis in children can persist for 1–2 months after the onset of symptoms. Macrolides do not effectively clear resistant strains from the nasopharynx of infected children, leading to prolonged carrier periods and increasing the risk of patients spreading the disease as a source of infection [26]. Additionally, prolonged, high-coverage vaccination pressure may drive adaptive changes in B. pertussis epidemic strains, possibly leading to immune evasion and contributing to the escalation of the epidemic.