Expert consensus on competency enhancement of pertussis prevention, diagnosis, and management for healthcare professionals through medical-preventive integration

Abstract

As pertussis resurgence has become a significant public health issue globally in recent years, the 2024 outbreak attracted substantial attention in China. Experts from various disciplines, including clinical medicine and public health, jointly formed an expert working group to analyze the current epidemiological characteristics of pertussis and bottleneck issues in the nation’s prevention and control of the infection. The working group developed the consensus and formulated recommendations and suggestions found here based on the concept of integrating medical care and prevention, evidence from the existing literature, and good principles of clinical practice. The group sought to enhance pertussis prevention, diagnosis, and management competencies for healthcare professionals by focusing on multidimensional core issues regarding the epidemiological characteristics of pertussis resurgence, the effectiveness and safety of vaccines containing pertussis and vaccination practices, and comprehensive case management and treatment and post-exposure prophylaxis regimens in the context of drug resistance background. It also recognized the importance of strengthening the collaborative monitoring between medical and prevention departments, as well as the monitoring level and public education through medical and preventive collaboration. The consensus aids in sustainably promoting and dynamically adjusting China’s pertussis prevention and control strategies.

Guideline Registration:

This expert consensus has been registered with the Guidelines International Network and is available in the International Guidelines Library (https://guidelines.ebmportal.com/expert-consensus-competency-enhancement-pertussis-prevention-diagnosis-and-management-healthcare).

1. Preface

As a global public health concern, the reemergence of pertussis has attracted significant attention in recent years, with the number of reported pertussis cases in China showing an upward trend since 2013. Following pertussis outbreaks in most regions of China in 2024, the National Disease Control and Prevention Administration issued the Pertussis Prevention and Control Plan in May 2024, which outlines the principles of “prevention first, combination of prevention and treatment, precise prevention and control, and rapid response,” as well as the operational requirements of “preventing infection, reducing severe cases, and decreasing deaths.”^[1] The plan aims to guide all regions in standardizing pertussis prevention and control efforts and improving the scientific level of precise interventions.

To implement China’s pertussis prevention and control requirements effectively and address the challenge of pertussis reemergence in the vaccine era, the Chinese Preventive Medicine Association – Working Committee on Pertussis Prevention and Control, in collaboration with the Chinese Society of Infectious Diseases, Chinese Medical Association, convened multidisciplinary experts to develop the consensus assembled here. The aim of the consensus was to enhance healthcare professionals’ capabilities in pertussis prevention, diagnosis, and treatment. Adhering to the principles of medical-preventive coordination and integration, the expert group comprehensively analyzed the current disease burden of pertussis in China, epidemiological trends, challenges encountered in clinical practice, and future prevention and control needs. Based on a review of domestic and international literature, evidence-based practice principles, and the experts’ collective clinical experience, this consensus was formulated to support the sustainable advancement and dynamic adjustment of China’s pertussis prevention and control strategies.

2. Methodology for consensus development

2.1. Consensus expert panel and conflict of interest management

The consensus panel comprised clinical specialists in infectious diseases, respiratory medicine, pediatric critical care medicine, clinical microbiology, and public health experts in infectious disease prevention and control and immunization programs. All panel members declared none of any potential financial or professional conflicts of interest and completed the conflict-of-interest questionnaire via the SurveyStar platform. This consensus has been registered with the International Guidelines Registry Network (URL: https://guidelines.ebmportal.com/expert-consensus-competency-enhancement-pertussis-prevention-diagnosis-and-management-healthcare).

2.2. Target audience

The recommendations in this consensus are applicable to healthcare professionals, with a primary focus on clinicians and nurses engaged in the diagnosis and treatment of infectious and respiratory diseases, clinical pharmacists, clinical microbiology specialists, infection control professionals, public health personnels responsible for infectious disease management, and healthcare providers involved in vaccination services. It is also intended for clinicians working in pediatric internal medicine, neonatology, pediatric critical care medicine, obstetrics, and community general practionners.

2.3. Identification of clinical questions

The selection of clinical questions was primarily based on key issues encountered in pertussis clinical diagnosis, treatment, and prevention practice; the disease prevention and treatment needs of patients, parents and the public; and controversial clinical topics raised in relevant domestic and international guidelines, research literature, and systematic reviews. A preliminary list of questions was developed by the core expert group and was subsequently discussed and refined through two rounds of full-panel discussions. Finally, the eight key clinical questions were identified in this consensus, which pertain to immunization, diagnosis, treatment, case management, and post-exposure prophylaxis for pertussis.

2.4. Evidence search, screening, and evaluation

The lead writing experts participated in the literature search and evidence collection based on the core questions identified, including domestic and international publications on pertussis surveillance, clinical studies, vaccine evaluation studies, and prevention and control strategies, as well as recently published high-quality systematic reviews and meta-analyses. The retrieved evidence was evaluated before citation by panel chairs based on the quality of the literature and the representativeness of the study. The writing expert group also retrieved high-quality guideline or consensus developed by authoritative organizations and official pertussis surveillance data reports, as well as relevant documents published on the websites of authoritative organizations for reference to formulate consensus statement and recommendation. The primary search terms included “pertussis,” “whooping cough,” “severe pertussis,” “epidemiology,” “surveillance,” “diagnosis,” “treatment/management,” “case management,” “antibiotic/antimicrobial treatment therapy,” “prevention,” “postexposure prophylaxis,” “pertussis vaccine,” “vaccine effectiveness,” “vaccine safety,” “vaccine hesitancy,” and “vaccination strategy.” “China,” “consensus,” and “guideline” were used as combined keywords. A systematic search was conducted in the PubMed, Chinese National Knowledge Internet (CNKI), and Wanfang Data databases, covering the period from database inception to June 30, 2026.

2.5. Formulation of consensus statements and recommendations

The core expert group formulated the consensus recommendations based on research evidence, findings from meta-analyses, and systematic reviews, combined with officially published authoritative data and recommendations from high-quality evidence-based guidelines and consensus. Full consideration was given to China’s national context and clinical practice principles. After their initial formulation, the draft recommendations were reviewed by the entire expert panel. A consensus was considered achieved when the approval rate reached ≥ 80%. For recommendations with an approval rate below 80% or that prompted significant controversies or dissenting opinions, the lead writing experts presented the rationale and supplementary evidence. The recommendations were revised as appropriate and recirculated to the full expert panel for further review until consensus was reached.

The recommendations are categorized as strong or weak. A recommendation is considered strong when an intervention’s benefits significantly outweigh its unfavorable effects, the certainty in the evidence is high, stakeholder values and preferences are well aligned, and cost-effectiveness is favorable. A recommendation is considered weak when the intervention’s benefits and harms for the target population are closely balanced, necessitating joint decision-making by clinicians and patients based on individual circumstances, or when the intervention should be applied to the target population or the specific circumstances under the stated condition.^[2] Strong recommendations are expressed as “is recommended,” whereas weak recommendations are expressed as “is suggested.”

3. Key questions and expert consensus

Question 1: How should healthcare professionals understand the “reemergence of pertussis” and its epidemiological characteristics in China in recent years, given the high coverage rates of pertussis-containing vaccines among children?

Consensus statement: Significant regional disparities exist in the reported incidence of pertussis in China, and the reported incidence among adolescents and adults is substantially underestimated. Over the past decade, clinical isolates of Bordetella pertussis from various regions have displayed widespread resistance to macrolide antimicrobial agents. Overall, the epidemiological pattern increasingly resembles the reemergence of pertussis previously observed in developed countries. This pattern is characterized by: (1) periodic fluctuations in overall incidence despite maintaining high childhood vaccination coverage; (2) the highest incidence (as well as the highest risk of severe disease and death) in infants under 1 year old who have not yet received pertussis-containing vaccines or completed primary series of immunization; (3) a marked increase in reported cases among children aged 4–11 years old, who constituted the predominant affected population during the 2024 outbreak; (4) increased risk of infection among school-aged children, adolescents, and adults due to waning vaccine-induced protective immunity, who predominantly present with mild atypical, subclinical, or asymptomatic manifestations and serve as the primary sources of occult transmission within communities and households.

Literature review: In the early 1990s, following the sequential replacement of whole-cell pertussis vaccines (wPV) with acellular pertussis vaccines (aPV) in the developed countries such as the United States and Europe, the issue of pertussis reemergence began to draw attention.^[3,4] Between 2023 and 2025, countries in Europe, the Americas, and the Western Pacific region reported pertussis cases surging tens to hundreds of times higher than in previous years.^[5] In 2024, China reported 476,690 pertussis cases and 30 deaths,^[6] marking the highest reported level in nearly four decades, ranking first globally (Figure 1).^[7,8] Since 2005, China has implemented lot release of the diphtheria-tetanus-acellular pertussis (DTaP) combined vaccine, and from 2007 onward, DTaP gradually replaced diphtheria-tetanus-whole-cell pertussis vaccine (DTwP), with the transition completed by 2013.^[8,9] This period coincided with heightened global attention to pertussis reemergence in developed countries.^[3,10] After 2013, some regions in China that proactively conducted pertussis surveillance observed an upward trend in reported cases, whereas other regions remained in a “relatively static” state. This regional disparity reflects the influence of subjective and objective factors on reported pertussis incidence, including the emphasis placed on active surveillance and testing, population immunity levels, and prevention and control measures.^[4] National pertussis surveillance data for 2024 indicate that epidemic intensities varied considerably across different administrative regions and that, overall, the incidence of pertussis at the current stage remains significantly underestimated. Active surveillance data in Yongcheng City, Henan Province, during 2021–2022 showed that the incidence in the community population was 54.89/100,000,^[11] which is approximately 27 times higher than concurrent passive surveillance reported incidence (2.60/100,000) for the same period across the entire province.^[12] Similarly, community-based active surveillance in Tianjin reported an annual community incidence (23.52/100,000) that was 16.22 times higher than hospital-reported figures during the same period.^[13]

Figure 1.

Global and China’s pertussis reported cases and three-dose diphtheria tetanus toxoid and pertussis (DTP) vaccination coverage rate (1980–2025).^[7,8] 1978: DTwP vaccine was incorporated into the National Immunization Program; 2005: China initiated batch certification of DTaP; 2007: Phased transition from DTwP to DTaP; 2013: DTwP was completely replaced by DTaP; 2021: Expert consensus on the China Pertussis Initiative; 2023: Pertussis Prevention and Control Manual; Pertussis Diagnosis and Treatment Plan (2023 Edition); 2024: Pertussis Control Scheme (2024 Version); China Guidelines for Pertussis Diagnosis, Treatment and Prevention (2024 Version). DTaP: Diphtheria-tetanus-acellular pertussis, DTwP: Diphtheria-tetanus-whole cellular pertussis.

Research data indicate that nearly all severe and fatal pertussis cases in China occur in infants under three months of age who have not yet initiated pertussis vaccination, as well as in infants who have not completed the primary immunization series.^[14,15,16] Between 2018 and 2022, severe pertussis cases in China among infants accounted for 58.10%–67.50%, 27.50%–31.28%, and 5.00%–10.62% in age group 0–2 months, 3–5 months, and 6–11 months, respectively.^[14,15] Infants under 3 months of age are more likely to develop severe complications, resulting in longer hospital stays, higher case-fatality rates,^[17,18,19] and greater economic burden.^{[19,20,21,22,23]} Maternal–infant paired serological studies have shown that approximately 98% of postpartum women and 96%–98% of neonates in China have serum pertussis antibody levels below protective thresholds or are seronegative,^[24,25] which suggests that maternally derived antibodies do not provide sufficient immune protection for neonates, rendering them especially susceptible to infection before the vaccine protection window is established.

The upward trend in pertussis cases among school-aged children, adolescents, and adults also warrants attention. During the 2024 pertussis outbreak, children aged 4–11 years became the primary susceptible population,^[26] and the number of cases among adolescents and adults was significantly higher than that in previous years.^[26,27] The progressive accumulation of susceptible individuals suggests that protective antibodies are waning over time. Numerous studies have demonstrated that immunity acquired through natural infection and vaccination lasts for 4–20 years and 4–12 years, respectively.^[28] The three-dose primary series of the aPV-containing combination vaccine currently used in China achieves approximately 90% protective efficacy within 1–2 years after the completion of primary immunization at 5–6 months; however, protection steadily declines over time,^[29,30] falling to approximately 50% at 4–5 years of age.^[31,32] In the vaccine era, although the overall incidence of pertussis has been substantially reduced, the boosting effect of natural infection on population immunity has been weakened, resulting in larger older age cohorts who have lost vaccine-derived protection. Therefore, when pertussis reemerges or outbreaks occur, the elevated incidence in infants indirectly reflects increasing infection and incidence rates in older age groups. Seroepidemiological survey data from five provinces and municipalities in China (Beijing, Chongqing, Guangdong, Shanghai, and Tianjin) between February 2017 and February 2018 showed that serum pertussis toxin immunoglobulin G (anti-PT-IgG) concentrations in 5-year-old children reached the nadir levels, and the seropositivity rate (anti-PT-IgG ≥ 40 IU/mL) among children aged ≥ 6 years was only 9.0%.^[33] A 2024 systematic review in China, including studies published from January 2010 to June 2023, reported that the seropositivity rate for anti-PT-IgG among all healthy populations was 7.06% (95% confidence interval (CI): 5.50%–9.07%), with overall low levels observed in preschool children, school-aged children, adolescents, women of childbearing age, and adults, with particularly low levels in school-aged children and young adults.^[34] A study from Henan Province reported a total seropositivity rate for anti-PT-IgG (≥ 20 IU/mL) of 18.61% in 2024.^[35] The low levels of protective antibodies in the Chinese population increase the risk of pertussis infection.

Adolescents and adults who have been previously vaccinated typically present with relatively mild symptoms following infection^[36] or may be asymptomatic,^[37] but they serve as major sources of occult transmission, increasing the risk of pertussis spread within families, institutions, and communities.^[38] In Tianjin, during 2010–2012, 85.33% of infections were reported to involve household clustering, predominantly following a transmission pattern from adults to infants (67.19%), with parents accounting for 78.44% of these transmissions.^[39] During the 2024 outbreak, pediatric pertussis surveillance studies in epidemic areas revealed that 64% of child cases’ family members confirmed to have Bordetella pertussis infection.^[26] A 2024 study from China reported that in single-child families, adults were the primary source of infection for infants (46.3%), whereas in multi-child families, siblings constituted the main source (51.4%), followed by adults (32.1%).^[40]

A potential contributing factor to the 2024 pertussis reemergence in China may have been the widespread resistance of Bordetella pertussis to traditional first-line macrolide antimicrobial agents, which exacerbates pathogen transmission.^[26,41] Although clinical isolates of Bordetella pertussis from northern China during 2000–2008 were uniformly susceptible to macrolides, since 2013, the macrolide resistance rate among isolates has reached 85.2%–94.4%,^[42,43,44] and in 2024, resistance rates approached 100%, with high-level resistance characterized by minimum inhibitory concentrations (MIC) > 256 μg/mL.^{[26,45,46,47]} A 2024 multicenter study in China found that the non-vaccine-type ptxP3-carrying MT28 clone had become the predominant circulating strain (accounting for 92.6%), with a PRN deficiency rate of 37.1%. Despite in the context of this predominant circulation of variant strains, breakthrough infections among infants who had completed primary immunization and toddlers who had received booster doses were rare.^[26] PRN-deficient strains have also been predominant in European and American countries^[41]; however, under such circumstances, case-control studies have not suggested the diminished protective efficacy of DTaP vaccines against the disease.^[48] In response to the issue of pertussis reemergence, developed countries such as in Europe and America have optimized and adjusted their immunization strategies, which was also recommended by the World Health Organization.^[49]

In summary, the primary factors underlying the reemergence of pertussis in China are related to the limited durability of immune protection conferred by pertussis-containing vaccines, shifts in transmission patterns, and strain resistance, with enhanced diagnostic and surveillance capacities also contributing to increased case detection and reporting.^[4,50] Under these evolving circumstances, healthcare professionals should proactively enhance their understanding of pertussis prevention and control, respond actively to the infection’s challenges, and implement scientifically based prevention and control measures.

Question 2: How should healthcare professionals understand the protective effects and limitations of pertussis-containing vaccines?

Consensus statement: (1) The childhood DTaP vaccination program remains the fundamental safeguard that substantially reduces pertussis incidence and mortality and maintains them at relatively low levels over the long term. (2) Early, timely, and complete vaccination with pertussis-containing vaccines at high coverage rates is key to effectively preventing pertussis epidemics and severe infections in infants. (3) Regardless of the manufacturing process and antigen components of the DTaP vaccine, completing the three-dose primary series in infants provides good protective efficacy against pertussis within 1–2 years, though it does not completely prevent asymptomatic infection. (4) Because the protective effectiveness of pertussis-containing vaccines declines over time, decreasing by approximately 50% at 4–5 years of age, a booster dose at 6 years of age is important for enhancing the immunity levels of school-aged children.

Literature review: The pertussis-containing vaccines used globally primarily include component-purified aPV, co-purified aPV, and wPV.^[49,51] DTaP-based combination vaccines are currently a key focus of research and development in China and represent a future direction for application.^[51,52] WHO data indicate that since the implementation of large-scale vaccination programs in the 1950s–1960s, the global incidence of pertussis has declined by more than 90%.^[49,53] Following the introduction of the childhood Expanded Program on Immunization in China in 1978, pertussis incidence and mortality decreased by over 99%.^[54] Available evidence demonstrates that vaccination with pertussis-containing vaccines can provide effective immune protection, regardless of the manufacturing process.^[55] The vaccine effectiveness (VE) of domestic co-purified DTaP against pertussis in infants and toddlers up to 24 months of age was 24.1%, 45.5%, 57.9%, and 87.1% following 1 to 4 doses, respectively; the VE against pertussis-related hospitalization was 25.6%, 63.2%, 60.3%, and 86.6%, respectively.^[56] A large-scale retrospective cohort study in Zhejiang Province showed that the protective efficacy of a 2-component purified pentavalent vaccine (DTaP-IPV//Hib) following 1 to 3 primary doses was 59.8%, 89.0%, and 90.8%, respectively.^[57] A Swiss case-cohort study demonstrated that the VE of 1 to 4 doses of the component-purified pertussis vaccine against pertussis-related hospitalization in children under 2 years of age was 42%, 84%, 98%, and 100%, respectively.^[58] Studies from Mexico and Panama confirmed that the VE of 3-dose pentavalent vaccine exceeded 90%.^[59,60]

The above findings indicate that, compared with vaccines such as measles vaccine, the protective effectiveness of both wPV and aPV has certain limitations. While some studies have shown that aPV vaccination can prevent symptomatic infection and severe disease, animal studies have found that baboons vaccinated with aPV failed to prevent colonization and transmission.^[61] A field study of a high school-based outbreak in the United States in 2019 found that high school students who had been vaccinated with aPV had asymptomatic infections (1.7%, with a median interval of 5.1 years from the last vaccination to study enrollment).^[62] Therefore, childhood vaccination with aPV may not effectively prevent asymptomatic infection or interrupt transmission. As protective antibodies wane significantly 4 years after the completion of childhood vaccination, relying solely on vaccination for preschool children is no longer sufficient to prevent pertussis epidemics. Since January 1, 2025, China has adjusted its immunization schedule to include DTaP doses at 2, 4, 6, 18 months and 6 years of age to optimize its vaccination strategy.^[63] However, there remains a need to explore selective immunization strategies for high-risk populations, strengthen immune protection barriers, and further protect susceptible populations. Optimizing the life-course immunization strategy for pertussis vaccines is an important supplement to sustained prevention and control efforts, including, for example, maternal vaccination during pregnancy to provide early protection for newborn infants and booster immunization for school-aged children, adolescents, and even certain key adult populations.

WHO recommends that pregnant women receive one dose of the tetanus, reduced diphtheria and acellular pertussis (Tdap) vaccine during the second or third trimester of pregnancy to provide early protection for young infants by enhancing maternally derived antibody levels.^[49] Seroepidemiological data from China indicate that the vast majority of pregnant women and their infants under 2 months of age are virtually unprotected and fall within the window of no vaccine-induced immunity.^[24,25,64] A recent meta-analysis demonstrated that infants born to mothers vaccinated with pertussis-containing vaccines during pregnancy have higher antibody levels before their first scheduled immunization, with a protective efficacy of 85% (95% CI: 78%–89%) against pertussis in infants under 3 months of age. Moreover, DTaP vaccination during pregnancy is well tolerated and does not increase the risk of adverse pregnancy, delivery, or neonatal outcomes.^[65] Following the introduction of maternal pertussis vaccination in Australia, the reported incidence of pertussis in infants aged < 2 months declined significantly.^[66]

Canadian studies have similarly shown that adolescent Tdap vaccination is associated with a significant reduction in pertussis incidence.^[67] Adults who receive booster vaccination achieve higher antibody concentrations, and these concentrations remain elevated for more than 10 years.^[68] Given that healthcare professionals with high-risk exposure to pertussis frequently come into contact with high-risk susceptible groups, such as infants and immunocompromised individuals, the U.S. Centers for Disease Control and Prevention recommends that healthcare professionals complete the primary series and receive periodic booster vaccinations with pertussis-containing vaccines to reduce the risk of serving as occult sources of transmission due to atypical infection.^[69]

Question 3: How should healthcare professionals provide consultation and guidance on childhood vaccination with pertussis-containing vaccines?

Consensus recommendations: The panel recommends that (1) Healthcare professionals should inform parents correctly about the immunization schedule, contraindications, common adverse reactions, and their management principles for childhood pertussis-containing vaccines and emphasize the importance of “early, timely, and complete vaccination” for achieving effective protection. (2) Healthcare professionals should accurately address parents’ questions regarding category I (routine immunization program) pertussis-containing vaccines and category II (non-program) vaccines (such as the quadrivalent vaccine, pentavalent vaccine, and component trivalent vaccine) and provide adequate informed consent. (3) Healthcare professionals should provide standardized guidance on timely and complete vaccination with pertussis-containing vaccines for children with special health conditions.

Literature review: In the 1980s, safety concerns regarding wPV triggered widespread public concern and vaccine hesitancy in Japan, Europe, and the United States, resulting in pertussis outbreaks and epidemics in some countries due to decreased vaccination coverage.^[70] However, numerous studies indicate that these safety concerns are largely invalid. The analyses of surveillance data from the United States did not demonstrate a causal association between childhood DTwP vaccination and acute encephalopathy.^[71] In the 1990s, developed countries replaced wPV with aPV, and long-term population-based surveillance data from Japan and the United States confirmed the overall safety of aPV.^[72,73] Population-based surveillance studies from other countries have not found associations between DTaP vaccination and neurological conditions such as seizures,^[74] Guillain-Barré syndrome,^[75] or acute disseminated encephalomyelitis.^[76] Pertussis-containing vaccines have a favorable safety profile, and the incidence of adverse reactions following DTaP vaccination is significantly lower than that following DTwP.^[49]

In 2024, China’s surveillance report on adverse events following immunization (AEFI)^[77] showed that the reported incidence rates of AEFI (serious AEFI), general reactions, and abnormal reactions following vaccination with DTaP, DTaP-containing pentavalent vaccine, and quadrivalent vaccine were 161.83–218.83/100,000 doses (0.31–0.69/100,000 doses), 160.52–216.82/100,000 doses, and 0.67–1.31/100,000 doses, respectively. The reported incidence rates of fever (axillary temperature ≥38.6°C), redness/swelling (diameter >2.5 cm), and local induration (diameter >2.5 cm) were 24.54–33.50/100,000 doses, 70.66–126.94/100,000 doses, and 33.71–56.34/100,000 doses, respectively. The reported incidence rates of allergic reactions were 0.54–1.05/100,000 doses (no anaphylactic shock was reported; only 1 case of laryngeal edema occurred). Febrile seizures, seizures, Guillain-Barré syndrome, and sterile abscesses were rare, with reported incidence rates of 0–0.02/100,000 doses (0–5 cases).

A domestic phase IV randomized controlled trial conducted in 2023^[78] compared the immunogenicity and safety of co-purified DTaP versus diphtheria-tetanus (DT) vaccine in 6-year-old children. Immunogenicity at 28 days post-vaccination was favorable, and most adverse events associated with the co-purified DTaP vaccine were mild to moderate in severity, with no vaccine-related serious adverse events. The DTaP group reported more vaccine-related adverse events than the DT group within 28 days post-vaccination (23.75% vs. 9.17%, P < 0.001), with a higher incidence of expected local adverse events (21.67% vs. 7.08%, P < 0.001), among which swelling and redness were the most common. The incidence of expected systemic adverse events was also higher in the DTaP group than in the DT group (5.00% vs. 2.50%, P = 0.149), with fever being the most common.

This study provides important evidence supporting the replacement of DT with DTaP for 6-year-old children in China. According to the principles of AEFI management outlined in the Standards for Vaccination Practice (2023 Edition),^[79] for mild reactions, such as local and systemic general reactions, clinical treatment is generally not required, and general management guidance should be provided. For acute severe AEFI, such as acute anaphylactic reactions occurring during the onsite observation period post-vaccination, emergency resuscitation should be initiated immediately, and referral for treatment should be arranged when necessary. For other serious AEFI, vaccine recipients should be advised to seek timely medical attention at qualified healthcare facilities. For suspected psychogenic reactions or vaccination error-related reactions, early identification and appropriate management should be implemented.

A prominent issue in the practice of pertussis-containing vaccination in China is that contraindications and precautionary statements in vaccine package inserts often result in delayed vaccination for certain high-risk children, particularly those with encephalopathy.^[80] Vaccine package inserts significantly influence healthcare professionals’ recommendations and parents’ willingness to vaccinate.^[81,82] A prospective observational study in China showed that among 2,221 children with any neurological disorder, the age-appropriate DTaP/DT vaccination rate was only 32.9%.^[83] Among 347 children with genetic encephalopathy, immune-related encephalopathy, or epilepsy who were recommended for catch-up vaccination, 249 completed all catch-up vaccinations, including DTaP, within one year, and active surveillance reported no seizure exacerbation or worsening of the underlying disease.^[83] Based on substantial evidence, the Chinese Guidelines for the Diagnosis, Treatment, and Prevention of Pertussis (2024 Edition) strongly recommends that children with neurological conditions can be routinely vaccinated with pertussis-containing vaccines when their disease is stably controlled or during the convalescent phase, and that preterm infants should receive their first dose of pertussis-containing vaccine according to their chronological age to achieve early protection.^[84] To further address the limitations of package insert statements and standardize vaccination for children with special health conditions, the 2026 edition of the National Immunization Program Vaccine Childhood Immunization Schedule and Explanatory Notes updated the general principles for vaccinating children with special health conditions based on the 2021 edition.^[85,86] It stated explicitly: (1) that preterm infants or low birth weight infants can be vaccinated according to their chronological age once medically assessed as stable; that febrile seizures in a stable phase are not a contraindication to vaccination; (2) that children with well-controlled epilepsy (including those on medication) can be vaccinated; and (3) that children with sequelae of central nervous system diseases, cerebral palsy, tic disorders, or cerebral dysplasia, among others, can be vaccinated if the diagnosis is confirmed and the condition is stable, even if they are receiving medication or rehabilitation therapy.

Currently, the vaccines available in China include the category I DTaP vaccine and category II vaccines (including the 3-component DTaP trivalent vaccine, quadrivalent vaccine, and pentavalent vaccine). The component-purified pentavalent vaccine induces higher and more durable PT/filamentous hemagglutinin (FHA) antibody levels than the domestic co-purified DTaP vaccine.^[87] Evaluating the trivalent, quadrivalent, and pentavalent vaccines, the 2024 Chinese pertussis guidelines^[84] found comparable protective efficacy and safety profiles. Compared with the trivalent vaccine, the pentavalent vaccine offers the added advantage of simultaneous protection against Haemophilus influenzae type b disease and poliomyelitis due to its multivalent composition, while the quadrivalent vaccine provides additional protection against Haemophilus influenzae type b disease. From the perspective of convenience, combination vaccines offer advantages by simplifying immunization schedules, reducing the number of injections, and improving vaccination coverage rates, and they represent a future development trend in China.^[51,52]

The 2015 WHO position paper explicitly recommends^[49] that all children should receive pertussis-containing vaccines, with the first dose administered as early as 6–8 weeks of age, and that coverage rates of ≥3 doses should be maintained at ≥90% to ensure high-level protection for children under 5 years of age. Following the 2024 pertussis outbreak in China, starting in 2025, the National Disease Control and Prevention Administration has advanced the first dose of the DTaP immunization schedule from 3 months to 2 months of age.^[63] Early and complete vaccination is crucial for achieving full vaccine protection, and each additional dose contributes to enhanced vaccine effectiveness, with subsequent booster doses extending the duration of protection.^[48]

Question 4: How should healthcare professionals standardize the comprehensive management and anti-infective treatment of pertussis cases?

Consensus recommendations: The panel recommends that (1) Healthcare professionals should strengthen early identification and nucleic acid testing for suspected pertussis cases (especially in older children, adolescents, and adults), promptly identify severe cases, standardize clinical diagnosis and treatment procedures, implement nosocomial infection control measures, guide patient isolation and family transmission prevention, and conduct online direct reporting in accordance with the management requirements for Category B notifiable infectious diseases. (2) For pertussis cases with pathogenetically confirmed susceptibility to macrolides, azithromycin is recommended as the first-line treatment, with a course of 3–5 days. (3) Regarding empirical anti-infective treatment, (i) sulfamethoxazole-trimethoprim (SMX-TMP) is recommended as the first-line empirical treatment for pertussis cases in children aged ≥2 months, with a usual course of 7 days. In regions with a high prevalence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (favism), such as in South and Southwest China, a family history of favism/hemolysis should be inquired about before treatment initiation, and G-6-PD enzyme activity screening should be performed when feasible. (ii) For patients in whom SMX-TMP is contraindicated or should be used with caution (those aged <2 months, pregnant women, breastfeeding women, those with severe hepatic or renal impairment, those with G-6-PD deficiency, those with severe allergy to SMX-TMP, or those infected with SMX-TMP resistant strains), levofloxacin is suggested as an oral alternative, with a usual course of 7 days. Use in children, pregnant women, and breastfeeding women should comply with off-label use regulations. (iii) For hospitalized infants aged <2 months and hospitalized patients lacking better oral alternative options, either cefoperazone-sulbactam or piperacillin-tazobactam is suggested for use on a case-by-case basis.

Literature review: Early recognition and diagnosis of pertussis cases by healthcare professionals is key to reducing transmission and minimizing the risk of severe disease. Effective antimicrobial treatment administered within 7 days of symptom onset can alleviate cough symptoms^[88]; treatment within 2 weeks, particularly within 7 days, can shorten the duration of cough^[89]; treatment within 2 weeks of onset can significantly reduce secondary transmission and secondary cases^[88,90,91]; and treatment with susceptible antimicrobial agents can reduce pulmonary complications^[89] and may lower the case-fatality rate in infants under 3 months of age.^[92] A previous study showed that the bacterial isolation rate in pertussis patients was 60% in the second week of illness, > 40% in the fourth week, and remained at 20% in the sixth week.^[93] Therefore, even though patients entering the paroxysmal phase 2–3 weeks after symptom onset may not benefit symptomatically from antimicrobial treatment, antimicrobial therapy is still recommended throughout the paroxysmal phase as it is beneficial for pathogen clearance and reduces ongoing transmission.

Given the current widespread macrolide resistance among circulating Bordetella pertussis strains in China, the 2024 guideline recommend SMX-TMP as the first-line empirical treatment for infected individuals aged ≥2 months and suggest that cefoperazone-sulbactam or piperacillin-tazobactam may be used in infants <2 months of age.^[84] This weak recommendation is primarily based on retrospective study findings^[94] (the mean interval from cough onset to culture-confirmed pertussis diagnosis was 17.1 ± 10.3 days; 72.1% had already received macrolide therapy; and 75.4% of clinical isolates were macrolide-resistant); the bacterial clearance rate at 2 weeks was higher in the cefoperazone-sulbactam or piperacillin-tazobactam monotherapy group than in the macrolide monotherapy group (96% vs. 50%), with no significant statistical difference in symptom improvement rates (93.8% vs. 86.7%). The 2005 U.S. guidelines,^[95] based on earlier clinical studies, recommend erythromycin or SMX-TMP for 10–14 days, azithromycin for 3–5 days, and clarithromycin for 7 days, and these recommendations have continued to be used.^[96] The 2024 United Kingdom^[97] and Australia^[98] pertussis management guidelines both recommend a 7-day short-course antimicrobial regimen (except for the 3–5-day azithromycin course).

A 2024 prospective cohort study in China indicated that levofloxacin is as effective as SMX-TMP for the treatment of pertussis in children.^[99] The study enrolled 193 outpatient children aged 1–16 years with pertussis (181 aged ≥5 years, 12 aged 1–4 years; 165 enrolled within 1–2 weeks of onset, 28 at 2–3 weeks). Of these, 109 received SMX-TMP (20 mg-4 mg/kg, twice daily) and 84 received levofloxacin (8–10 mg/kg, not exceeding 500 mg; once daily for children <5 years, twice daily for those ≥5 years) for 5–14 days. After 5–7 days of treatment, nasopharyngeal swab bacterial cultures converted to negative in both groups, with no difference in nucleic acid conversion rates (87.06% vs. 92.00%, P = 0.378), and paroxysmal cough and nocturnal cough symptoms improved markedly in nearly all patients, suggesting comparable efficacy between the two regimens. The incidence of rash was higher in the SMX-TMP group than in the levofloxacin group (8.36% vs. 1.19%, P = 0.059), and the gastrointestinal reactions were similar (1.16% vs. 0.91%, P = 1.000). Based on domestic studies and the latest international guidelines, a 7-day course of SMX-TMP is recommended for pertussis treatment, with the possibility of extending the course for severe and critical cases as clinically indicated. However, SMX-TMP is generally contraindicated in infants <2 months of age, with restrictions in China^[84] and the United States^[95,96] for infants <2 months, Japan^[100] for infants < 4 weeks, Australia^[98] for infants <1 month, and the United Kingdom^[97] for infants <6 weeks. During the 2025 pertussis epidemic in Japan, among 371 Bordetella pertussis isolates or clinical DNA samples tested in the third quarter (July to September), the detection rate of macrolide-resistant mutant strains (A2047G) was 79.5%.^[101] In response to the circulation of resistant strains, the National Center for Child Health and Development in Japan reported in 2025 that 6 infants aged 22–55 days received SMX-TMP for 14 days, with no significant adverse reactions observed. The Japanese authors suggested that in the context of high resistance rates, SMX-TMP may be a feasible alternative for treating severe pertussis in young infants (including off-label use in neonates), provided that bilirubin-related toxicity is closely monitored.^[102]

Furthermore, the emergence of Bordetella pertussis strains with intermediate susceptibility^[19,26] and resistance^[103] to SMX-TMP, as noted in domestic literature, warrants clinical attention and alternative treatment strategies should be considered. For patients with contraindications or for whom SMX-TMP is unsuitable, levofloxacin is a suggested option, based on the domestic prospective cohort study showing that levofloxacin has non-inferior susceptibility to Bordetella pertussis and non-inferior efficacy to SMX-TMP in treating pediatric pertussis, with lower adverse reaction rates.^[99] The Guiding Principles for Clinical Application of Antimicrobial Agents do not recommend fluoroquinolones for children under 18 years of age, pregnant women, or breastfeeding women, and their use should be avoided.^[104] Similarly, most drug package inserts warn that fluoroquinolones should not be used, should be avoided, or are contraindicated in children under 18 years of age.^[105] However, substantial real-world data have demonstrated that fluoroquinolone use in children (including neonates) is generally safe.^{[105,106,107]}. Accordingly, the 2017 Chinese expert consensus^[105] suggested that fluoroquinolones may be used in children when other safe and effective drugs are unavailable (e.g., multidrug-resistant infections) or in cases of severe allergy to other agents. A meta-analysis of observational studies involving 2,800 pregnant women reported that fluoroquinolone use for any reason (e.g., urinary tract infection) was not associated with significant differences in the incidence of birth defects, spontaneous abortion, or preterm birth compared with unexposed pregnant women.^[108] The U.S. LactMed® database indicates that levofloxacin concentrations in breast milk are significantly lower than the infant dose and are not expected to cause adverse effects in breastfed infants.^[109] Based on its safety evaluation, WHO includes levofloxacin in the WHO Model List of Essential Medicines for Children^[110] and recommends it as a first-line agent for treating drug-resistant tuberculosis in all children (without age restriction) and adults, including pregnant and breastfeeding women.^[110,111]

With the above evidence supporting the overall safety of levofloxacin for treating children and pregnant women, levofloxacin is suggested as an oral alternative for treating pertussis in children aged 0–17 years and adults. It should be noted that the use of SMX-TMP in infants <2 months of age and the use of levofloxacin in children <18 years constitute off-label use in China, and package inserts also caution against the use of these drugs in pregnant and breastfeeding patients.^[104] Therefore, this consensus explicitly specifies that such use should be considered only after a careful risk–benefit assessment, with signed informed consent from parents or patients, close monitoring for adverse reactions, and compliance with regulatory requirements for off-label use in special populations. Details on drug selection, dosage, administration, treatment duration, and precautions for antimicrobial pertussis therapy are summarized in Table 1.

Table 1.

Antimicrobial agents for treatment and post-exposure prophylaxis of pertussis: drug selection, dosage, and administration

Antimicrobial agents	Indications, dosage, and administrationa	Treatment courseb	Notes & precautions
Sulfamethoxazole- Trimethoprim (SMZ-TMP, 5:1)	1) Children ≥ 2 months: 48 mg/kg (40 mg SMZ-8 mg TMP)·kg–1·d–1 (max 1,920 mg), orally in two divided doses. Recommended for use in children ≥ 4 weeks by Japanese guidelines,[100] ≥ 6 months by Australian guidelines,[98] ≥ 1 month by UK guidelines,[97] ≥ 2 months by US guidelines.[95,96] 2) Children < 2 months: Contraindicated as per Chinese package insert. Fully inform guardians about benefits–risks; use only when potential benefit outweighs risks after informed consent. 3) Adults: 1,920 mg (1,600 mg SMZ-320 mg TMP)/d, orally in two divided doses. 4) Pregnancy and lactation: avoided for use as per Chinese package insert. Avoid in early-trimester pregnancy and within one month before delivery.[104] Use only when the potential benefits are expected to outweigh the risks, particularly when there are no alternative therapies.	7 days	1) In China, given the high prevalence of macrolide-resistance Bordetella pertussis, SMZ-TMP should be considered as the first-line choice for treatment and post-exposure prophylaxis in children ≥ 2 months and adults.[84] 2) Contraindicated for use in patients with severe hepatic and renal impairment, complete glucose-6-phosphate dehydrogenase (G6PD) deficiency and used with caution for partial deficiency; high doses may induce hemolysis.[104] The southern and southwestern China are regions with a high incidence of favism. Therefore, medication should be used with caution, and a detailed medical history should be reviewed before administration. 3) Monitor renal injury, crystalluria, hyperkalemia, allergy (especially drug-eruption), leukopenia, and thrombocytopenia; check liver function and blood routine.[84,104]
Azithromycin	1) Infants < 6 months: 10 mg·kg–1·d–1, single oral dose, 5 days. 2) Children ≥ 6 months: 10 mg·kg–1·d–1 (max 500 mg) for 3–5 days; or 10 mg/kg Day 1, 5 mg·kg–1·d–1 Days 2-5, single oral dose. 3) Adults: 500 mg/d for 3 days; or 500 mg Day 1, 250 mg/d Days 2–5, single oral dose.	3-5 days	1) Bordetella pertussis in China is extensively macrolide resistant. Macrolides should not be recommended for the empirical first-line therapy,[84] especially in severe cases. 2) For etiologically confirmed macrolide-susceptible pertussis; azithromycin is recommended as the preferred choice of the first-line drugs, otherwise not applicable.[84] 3) Use azithromycin with caution in patients with long QT syndrome. 4) Higher frequency of gastrointestinal adverse-event; risk of infantile hypertrophic pyloric stenosis in neonates; avoid in neonates.
Clarithromycin	1) Children ≥ 1 month: 15 mg·kg–1·d–1 (max 1 g), orally in two divided doses. 2) Adults: 1 g/day, orally in two divided doses.	7 days
Erythromycin	1) Children ≥ 1 month: 40 mg·kg–1·d–1 (max 2 g), orally in four divided doses. 2) Adults: 2 g/day, orally in four divided doses.	7 days
Levofloxacin	1) Children < 5 years: 15–20 mg·kg–1·d–1, orally in two divided doses. 2) Children ≥ 5 years: 10 mg·kg–1·d–1 (max 500 mg), single oral dose. 3) Adults: 500 mg, single oral dose. 4) Pregnancy and lactation: Avoided for use as per Chinese labeling; use only when no alternatives and when benefit outweighs fetal–infant risk.	7 days	1) As an oral alternative medication: If the patient is allergic to SMX-TMP, or has contraindications for use, or is not suitable for use. 2) As an alternative treatment option for treating macrolide-resistant Bordetella pertussis infection. 3) Informed consent required for children <18 years and pregnant or lactating women.
Cefoperazone-sulbactam (2:1)	1) Hospitalized infants < 2 months: 20–80 mg·kg–1·d–1 (cefoperazone component), intravenous, q8h (adjust for gestational age; q12h for <7-day-old neonates). 2) Conditionally used for hospitalized patients when no alternative appropriate oral regimens can be choice or available.	7 days	1) As alternative regimen for drug-resistant Bordetella pertussis infection in infants < 2 months of age. [84,112] 2) Not recommended for outpatient use. 3) High-quality prospective clinical studies are needed to further evaluate and confirm in vivo efficacy.
Piperacillin-tazobactam (8:1)	1) Hospitalized infants < 2 months: 240–300 mg·kg–1·d–1 (piperacillin component), intravenous, q8h. 2) Conditionally used for hospitalized patients when no alternative appropriate oral regimens can be choice or available.	7 days

^aAdministration: Oral route is preferred; intravenous infusion is an alternative for patients who are intolerant to oral therapy.

^bTreatment course: 7 days in general; may be extended to 10–14 days for severe cases.

To achieve the national goal of precise pertussis prevention and control, healthcare professionals should recognize suspected pertussis cases early in clinical practice and conduct etiological screening, facilitating the timely initiation of standardized anti-infective treatment and case management. Between 2021 and 2024, China consecutively issued the Expert Consensus on the China Pertussis Action Plan,^[4] the Pertussis Diagnosis and Treatment Protocol (2023 edition),^[112] the Chinese Guidelines for the Diagnosis, Treatment, and Prevention of Pertussis (2024 edition)^[84], and the Pertussis Prevention and Control Plan (2024 edition),^[1] which have enhanced pediatric healthcare professionals’ understanding of pertussis and promoted the application of pertussis nucleic acid diagnostic techniques in pediatric healthcare institutions. Although the 2024 pertussis reemergence drew nationwide attention from healthcare professionals to pertussis in children, the screening and testing of suspected pertussis cases in adults remains neglected. Most adult cases present with atypical manifestations, and etiological diagnosis is not routinely performed in healthcare facilities, often leading to missed diagnoses and, consequently, failure to receive timely diagnosis and appropriate treatment, which may also progress to severe disease. In 2024, a study from Shandong Province reported 24 cases of severe pertussis pneumonia confirmed by metagenomic next-generation sequencing of bronchoalveolar lavage fluid following hospital admission.^[113] As adult-infected cases are the primary transmitters of pertussis in the vaccine era,^[38] healthcare professionals should actively screen for adult pertussis, especially when encountering patients presenting with paroxysmal cough, cough lasting ≥2 weeks without fever and no improvement after treatment.

Since pertussis is a Category B notifiable infectious disease under the Law of the People’s Republic of China on the Prevention and Treatment of Infectious Diseases, healthcare professionals at all types of medical institutions should report suspected, clinically diagnosed, and confirmed pertussis cases online via the China Disease Prevention and Control Information System within 24 hours of the initial diagnosis. Cases should be updated based on laboratory results and disease progression, and those requiring intensive care unit admission should be reported promptly. In addition, healthcare professionals should cooperate with disease control agencies in epidemiological investigations and risk assessments for severe, fatal, and clustered cases, provide detailed medical records, and assist in identifying the source of infection and the scope of close contacts. Healthcare facilities admitting pertussis patients should strictly implement nosocomial infection control measures, including prescreening and triage, enhanced environmental disinfection (air disinfection in consultation rooms, cleaning and disinfection of surfaces, and disinfection of medical equipment), improved ventilation in patient consultation rooms and wards, and standard occupational protection for healthcare staff (proper wearing of masks, strict hand hygiene). Healthcare facilities should conduct training on pertussis diagnosis, treatment, and prevention for departments and healthcare professionals involved in pertussis care.

Comprehensive and standardized management of pertussis cases is the core measure to interrupt transmission and reducing severe disease and death. Drawing on authoritative evidence from the 2024 United Kingdom^[97] and Australian^[98] pertussis case management guidelines and China’s prevention and control plan,^[1] a stratified management system for healthcare professionals is proposed, with differentiated approaches for uncomplicated and severe cases. Uncomplicated cases should primarily be treated at home with self-isolation for at least 5 days after the initiation of effective antimicrobial therapy. For cases not receiving antimicrobial treatment, isolation should continue for at least 21 days after cough onset. During the isolation period, patients should avoid contact with high-risk populations, such as infants, young children, and pregnant women, wear a medical surgical mask when going out, and refrain from visits to crowded places, such as childcare facilities and hospitals. Severe cases should be hospitalized for isolation and treatment, and critical cases should promptly undergo multidisciplinary consultation involving infectious disease, respiratory, and critical care specialists to enhance medical management.

Question 5: How can healthcare professionals identify severe pertussis as early as possible in clinical practice and implement appropriate treatment measures?

Consensus recommendations: (1) To minimize the case-fatality rate, the panel recommended that healthcare professionals should strengthen their ability to identify infant and adult cases with risk factors for severe pertussis and to promptly initiate effective anti-infective therapy and comprehensive supportive care. (2) The panel recommended that supportive care for severe or critical cases should be implemented with appropriate indications. A short course of corticosteroids can be suggested for cases with severe paroxysmal coughing accompanied by choking episodes; exchange transfusion can be suggested in young infants with severe hyperleukocytosis (white blood cell count ≥50 × 10⁹/L, or ≥30 × 10⁹/L with progressive increase within 24 hours) complicated by pulmonary hypertension but without severe cardiopulmonary failure. High-dose intravenous immunoglobulin is not recommended.

Literature review: Pertussis remains one of the leading causes of vaccine-preventable deaths in infants worldwide, particularly in those under 3 months of age.^[114] Early identification of severe disease, prompt initiation of effective antimicrobial therapy, and comprehensive symptomatic and supportive care can minimize the case-fatality rate. Based on clinical research literature, risk factors for severe pertussis in infants and young children include^{[14,15,16,17,18,19,92,115,116,117,118,119,120]} (1) age ≤2 months (primary risk factor); (2) lack of vaccination orincomplete primary pertussis immunization series; (3) low birth weight and preterm; (4) white blood cell count significantly elevated ≥30 × 10⁹/L with progressive increase within 24 hours, with ≥50 × 10⁹/L serving as a critical warning indicator; (5) recurrent apneic episodes; (6) frequent cyanosis or choking; (7) frequent or persistent hypoxemia requiring oxygen therapy; (8) pneumonia with tachypnea; (9) seizures suggestive of pertussis encephalopathy; (10) pulmonary hypertension; and (11) severe chronic cardiopulmonary disease or neuromuscular disorders. Based on international studies, risk factors for severe adult pertussis include patients with chronic underlying conditions, such as asthma, chronic obstructive pulmonary disease, depression, immunodeficiency, and obesity, particularly those aged ≥65 years.^{[120,121,122,123]}

For suspected pertussis cases with the above risk factors for severe disease, early diagnosis and timely initiation of effective antimicrobial therapy are essential. Delayed antimicrobial treatment may lead to disease progression and poor outcomes in high-risk patients.^[92] Concurrently, appropriate comprehensive supportive care should be provided to reduce mortality and complications. Comprehensive supportive care primarily includes: (1) Airway management.^[112] For infants and young children with severe paroxysmal coughing, appropriate humidification of the airways and clearance of airway secretions are recommended to prevent airway obstruction. Routine suctioning is not recommended as it stimulates the respiratory tract and may induce airway spasm. Nasogastric feeding should be considered to prevent choking caused by post-tussive vomiting. (2) Systemic corticosteroids. For infants and young children with severe paroxysmal coughing, a short course (7–10 days) of systemic corticosteroids (e.g., prednisone 0.5–2.0 mg·kg^–1·d^–1) may be considered, which may reduce the frequency of choking episodes and paroxysmal coughing, as well as the duration of cough, with a very low probability of corticosteroid-related adverse events.^[84] (3) Exchange transfusion should be used with caution.^[84] Although, theoretically, hyperleukocytosis may contribute to pulmonary hypertension and reducing white blood cell levels may delay or halt disease progression, current evidence does not confirm the clinical benefits of exchange transfusion. Moreover, in infants who have already progressed to cardiopulmonary failure, hypotension, or shock, exchange transfusion may increase the risk of mortality^[124,125] or not reverse the prognosis of critical cases.^{[118,124,125,126]} The 2024 Chinese guidelines recommend^[84] that for severe pertussis in infants and young children, when peripheral white blood cell count >50 × 10⁹/L, or >30 × 10⁹/L with rapid progressive elevation and accompanied by pulmonary hypertension, exchange transfusion may be considered based on the patient’s condition, disease progression, and available medical resources, provided that severe cardiopulmonary insufficiency has not yet developed.

Regarding the supportive treatment for severe pertussis cases, intravenous immunoglobulin is not recommended. Serum anti-PT protective antibody levels in the healthy Chinese population are low.^[33,34] In theory, intravenous immunoglobulin therapy does not provide neutralizing effects against the toxin, and it is also costly. Early controlled studies showed that the administration of pertussis-specific immunoglobulin approximately one week after the onset of paroxysmal cough in children with pertussis did not shorten the duration of the paroxysmal phase compared with no treatment^[127] and did not improve paroxysmal coughing, apnea, bradycardia, or oxygen desaturation compared with placebo.^[128]

Question 6: How should healthcare professionals provide professional guidance regarding post-exposure prophylaxis (PEP) for the close contacts of pertussis cases?

Consensus recommendations: The aim of pertussis PEP is to interrupt pathogen transmission, prevent disease onset in high-risk exposed individuals, and minimize the occurrence of severe disease and death. (1) The panel suggested that the following close contacts of pertussis cases during the infectious period (from 1 week before symptom onset to 2–3 weeks after onset in untreated patients) receive PEP: (i) high-risk individuals for severe disease, including unvaccinated infants or infants who have not completed the 3-dose primary series and patients with severe chronic cardiopulmonary disease, immunodeficiency, or other severe underlying conditions; (ii) staff in key settings with exposure to infants under 6 months of age, including household members, healthcare workers in neonatal/pediatric wards, obstetrics departments, and rehabilitation wards, and staff in postpartum care centers, childcare facilities, and children’s welfare institutions; (iii) women in the third trimester of pregnancy (especially at 32–37 weeks of gestation) and their cohabiting family members or caregivers. (2) Regarding antimicrobial selection for PEP: (i) if the pathogen is confirmed to be susceptible to macrolides, azithromycin is recommended as the first choice; (ii) If drug susceptibility cannot be determined, SMX-TMP is recommended empirically as the first-line prophylactic treatment for exposed individuals aged ≥ 2 months. For infants <2 months of age, pregnant women, and breastfeeding women, levofloxacin or SMX-TMP may be considered on a case-by-case basis in accordance with off-label use regulations, after a careful risk–benefit assessment and with informed consent; alternatively, quarantine and observation may be implemented, with prompt etiological testing if symptoms develop, and early treatment initiation upon confirmed diagnosis; (iii) The prophylactic antimicrobial choice, dosing and durationand precautions are the same as those for therapeutic treatment, administered orally (see Table 1 for details). (3) It is suggested that close contacts be followed up and observed for 21 days after initiating PEP and that appropriate respiratory protective measures when they come into contact with high-risk individuals for severe disease.

Literature review: Pertussis is highly contagious, with high secondary infection rates in households and closed settings. A 1998 German study showed that when the index case in a household was a child, 69% of unvaccinated children aged 6–47 months and 31% of adults developed symptomatic infection.^[129] A 1995 Canadian cohort study showed that secondary attack rates following household exposure decreased with age: 65% in children aged <2 years, 54% in children aged 2–4 years, 29% in children aged 5–9 years, 16%–19% in individuals aged 10–29 years, and 6%–8% in individuals aged ≥30 years.^[130] A 1988 U.S. study^[88] reported that during a pertussis outbreak in a facility for individuals with disabilities, the infection rate among patients in the affected wards ranged from 6% to 91%, of which 87% were symptomatic infections. Initiation of erythromycin treatment or PEP at ≤2 weeks and ≥4 weeks after the onset of the index case was effective in reducing transmission risk and disease severity, with a significant difference in infection rates (16% vs. 75%, P < 10^–6). A recent Ethiopian study showed that contact history (odds ratio (OR) = 3.44, 95% CI: 1.69–5.19) was one of the primary predictors of pertussis outbreaks.^[131]

Appropriate PEP measures should be taken into consideration in reducing transmission and protecting high-risk individuals for severe disease.

The efficacy of PEP for transmission reduction remains inconsistent. Two early randomized controlled trials (RCT) from the United Kingdom (1981)^[132] and Canada (1999)^[133] showed that compared with the no-prophylaxis group, erythromycin prophylaxis in household contacts may reduce the risk of culture-confirmed secondary pertussis by 33% (RCT = 2, n = 391, relative risk (RR) = 0.67, 95% CI: 0.25–1.78, moderate-certainty evidence), although the difference in pertussis incidence between the two groups was not statistically significant (3.5% vs. 5.2%, P = 0.23).^[89] A U.S. RCT^[134] involving 92 healthcare professionals who had received DTaP vaccine within the preceding 4 years showed no statistically significant difference in laboratory-confirmed asymptomatic pertussis infection rates between the azithromycin prophylaxis group and the untreated group (2.5% vs. 9.1%, P = 0.54). Four retrospective household observational studies^{[90,91,130,135]} demonstrated that prophylactic treatment with erythromycin or azithromycin initiated within 3 weeks (mostly around 2 weeks) after household exposure to the index case effectively reduced secondary cases and household transmission, whereas prophylaxis after 3 weeks was ineffective. Among these, a Canadian cohort study reported that the secondary attack rate in households was 17% in the erythromycin prophylaxis group and 25% in the no-prophylaxis group, with no variation by age or immune status. The effectiveness of prophylaxis initiated before the appearance of secondary cases in the household was significantly superior to that initiated after secondary cases had already occurred (secondary attack rates of 4% and 35%, respectively, P < 0.001).^[130] A 2020 Spanish retrospective cohort study included 476 primary pertussis cases and their 1,975 household contacts; 4.5% of contacts were confirmed to have pertussis.^[135] The effectiveness of PEP initiated within 7 days after the onset of the primary case was 89.0% (95% CI: 6.7%–98.7%), 46.4% (95% CI: −114.9% to 75.4%) at 8–14 days, 2.8% (95% CI: −171.3% to 65.2%) at 15–21 days, and was ineffective after >21 days.^[135] A 2015 modeling study showed that post-exposure prophylaxis in household settings was cost-effective compared with no prophylaxis.^[136]

Based on the above multiple lines of evidence, guidelines from China,^[1,84] the United States,^[95,96,137] the United Kingdom,^[97] and Australia^[98] consistently recommend PEP to protect high-risk infants for severe disease and to prevent death or serious complications from severe pertussis infection. Recommended PEP candidates include high-risk exposed individuals (unvaccinated infants, infants who have not completed the primary immunization series); exposed individuals in key transmission settings or facilities who may transmit infection to high-risk susceptible infants; and pregnant women in the third trimester and their household members or close contacts. For clustered cases or outbreaks in key settings (childcare facilities, schools, welfare institutions, elderly care facilities, inpatient wards), routine PEP is not recommended, except for specific individuals (contacts with household-like exposure, where pertussis in the exposed individual could lead to serious consequences, or those in daily close contact with individuals at high risk of severe disease).

The antimicrobial selection, dosage, and duration for PEP are the same as those for the therapeutic treatment of pertussis. If the close contact is an infant <2 months of age, a pregnant woman, or a breastfeeding woman, individualized prophylactic suggestions should be provided under specialist guidance. After a careful risk–benefit assessment and with informed consent from the parents or the individual, levofloxacin or SMX-TMP may be considered on a case-by-case basis in accordance with off-label use regulations. Levofloxacin (for a 6-month course) has been recommended by WHO guidelines as the preferred prophylactic treatment for drug-resistant tuberculosis infection in all children and adults.^[138] Close contacts receiving PEP should be observed and quarantined for 21 days after the last exposure (the maximum incubation period for pertussis). If cough symptoms develop, evaluation should be performed, and pertussis pathogen screening should be conducted when feasible. For exposed individuals in key settings, PCR screening may be performed to identify infected individuals early and prevent further transmission. Based on multiple authoritative domestic and international guidelines,^[1,84,96,97] the definition of a close contact is an individual who has had close contact (within 1 meter, for at least 1 continuous hour) with a pertussis case from 1 week before cough onset to 5 days after treatment initiation (or within 3 weeks after onset in untreated patients, or within 2 weeks of cough onset) without protective measures, including those who share living, learning, working, or caregiving spaces.

Question 7: How can healthcare institutions strengthen medical-preventive coordination to jointly improve pertussis surveillance?

Consensus recommendations: (1) The panel suggested that medical institutions at all levels establish routine, multi-dimensional information-sharing and collaboration mechanisms with disease control and prevention agencies and implement the prevention and control measures such as “active detection, active reporting, and active screening.” (2) The panel suggested that medical institutions continuously improve the laboratory pathogen testing system, promote the availability of pertussis pathogen nucleic acid testing and resistance gene detection, and achieve precise diagnosis and timely reporting of cases. Hospitals should conduct the surveillance of drug resistance in pertussis where feasible.

Literature review: Pertussis case reporting in China currently relies primarily on the infectious disease network direct reporting information system, which is predominantly passive surveillance based on case reports from hospitals at all levels, with significant discrepancies between active and passive surveillance reported incidence rates. The establishment of an effective monitoring system is the core of pertussis prevention and control. Strengthening the coordination mechanism between healthcare institutions and disease control departments and enhancing laboratory diagnostic capacity are key strategies for improving pertussis surveillance and prevention and control efficiency.^[1,139] The Pertussis Prevention and Control Plan (2024) issued by the National Disease Control and Prevention Administration^[1] calls for the implementation of multi-channel surveillance and early warning, as well as enhanced epidemic analysis and risk assessment. It also requires that medical institutions organize training for healthcare professionals—especially those in key departments, such as outpatient and emergency services, neonatology, pediatrics, respiratory medicine, and critical care on pertussis prevention, control, diagnosis, and treatment knowledge and skills.

In 2018, WHO defined the objectives of pertussis surveillance standards as follows^[139]: (1) monitoring disease burden and the impact of the pertussis vaccination program, with a special focus on understanding the morbidity and mortality in children <5 years of age; (2) generating data to inform vaccine schedule and delivery strategy decisions to optimize the impact of vaccination; and (3) timely detecting and guiding public health response to outbreaks of pertussis. The European Union,^[140], as well as countries including the United Kingdom,^[141] the United States,^[142] Japan,^[143] Canada,^[144] Australia,^[145] and China have established routine pertussis surveillance systems. In 2012, the European Union, which maintains one of the world’s most comprehensive pertussis monitoring systems, developed a unified case definition for pertussis surveillance.^[140] Most member states conduct routine surveillance in accordance with the standards set by the European Centre for Disease Prevention and Control (ECDC) and submit surveillance data to the ECDC at least annually. The United States,^[142] based on the National Notifiable Diseases Surveillance System (NNDSS), has launched the Enhanced Pertussis Surveillance (EPS) program, covering seven pilot states. Medical institutions and laboratories are required to report confirmed cases to the CDC through the electronic system, while staff interview patients and healthcare providers to complete case information and collect strains. Many countries including China have linked pertussis surveillance with vaccination systems, analyzing case vaccination histories to assess vaccine effectiveness and identifying gaps in prevention and control, thereby providing critical evidence for the dynamic adjustment of immunization strategies.

Crucial to formulating disease prevention and control strategies, pertussis surveillance covers all aspects of case identification, reporting, source tracing, and prevention and control. To strengthen medical-preventive coordination, first, clinical departments and disease control agencies should enhance coordination in case identification and reporting, standardize diagnostic criteria, and reduce missed and misdiagnosed cases. Medical institutions at all levels should report pertussis cases identified during diagnosis and treatment in a timely and standardized manner in accordance with laws and regulations. Second, laboratories and disease control agencies should deepen cooperation in testing, and source tracing. Clinical laboratories in secondary and above medical institutions should possess pertussis nucleic acid screening capabilities and conduct active surveillance. Sentinel hospitals are responsible for collecting and submitting samples, while network laboratories undertake nucleic acid testing, pathogen identification, gene sequencing, and information reporting. Laboratories and CDC should establish strain typing sharing mechanisms, dynamically monitor strain variation, assess vaccine immune escape, and jointly conduct source tracing among close contacts. Medical institutions and CDC should improve their training mechanisms to enable join monitoring through medical-preventive cooperation. Meanwhile, both parties jointly conduct surveillance data analysis and risk assessment, and coordinate vaccination and clinical interventions to provide a basis for precise prevention and control.

Question 8: How can healthcare professionals play an important role in public education on pertussis prevention and control?

Consensus recommendations: Healthcare professionals are the main force for the public to obtain scientific knowledge about diseases and vaccines, and they are also important advocates for building public confidence in vaccines. The panel suggested that medical institutions at all levels integrate pertussis health education into routine clinical services (including daily diagnosis and treatment of patients with cough, prenatal check-ups, health education, and child health care), continuously strengthen public awareness of the characteristics and harms of pertussis disease, promote public understanding of the life-course immunization strategy for pertussis vaccines, and facilitate translation into actual vaccination behavior.

Literature review: The Pertussis Prevention and Control Plan (2024) issued by the National Disease Control and Prevention Administration states that strengthening vaccination and health education for key populations and in key settings is an overall requirement for pertussis prevention and control.^[1] Missed diagnosis and misdiagnosis of pertussis remain the prominent clinical issues, particularly in cases with atypical cough symptoms or in adults. Therefore, as well as building their own awareness of pertussis, healthcare professionals in relevant specialties, such as pediatrics, general practice, infectious diseases, and respiratory medicine, have a responsibility to educate the public and patients on pertussis disease. In addition, healthcare professionals can be involved in health education activities in key settings such as postpartum care centers, childcare facilities, primary and secondary schools, children’s welfare institutions, and juvenile protection agencies. In such settings, they can guide staffs, postpartum women, faculty members, and students to acquire pertussis prevention knowledge, enhancing their awareness prevention and proactive healthcare-seeking, practicing daily self-protection and health monitoring, and cooperating with prevention and control efforts.

Timely and complete vaccination with pertussis-containing vaccines is an important prevention and control measure. In clinical practice, vaccine hesitancy is a primary cause of insufficient vaccination coverage and is closely associated with outbreaks of vaccine-preventable diseases. Studies have shown that while parents obtain information from variou sources to inform their vaccination decisions, they regard consider pediatricians and other clinicians as the most reliable source of vaccine information.^[146] Therefore, effective communication between healthcare professionals and patients regarding vaccination is essential to address parental concerns and promote vaccine acceptance.^[147] Available evidence indicates that strong, high-quality vaccination recommendations from clinicians are an effective communication strategy for improving vaccination coverage.^[148] In terms of service models, embedding pertussis education into routine clinical services (e.g., mandatory discussion points in prenatal visits, automatic reminders in child health clinics, and standardized discharge education information packages), supplemented by appointment reminders and convenient on-site vaccination services, can achieve more stable, sustained, and broad-reaching public education effects, and further translate vaccine recommendations into actual vaccination behavior.^[149]

Since China will continue to face the public health challenge of potential pertussis resurgence, the immunization strategy requires further refinement. As vaccine-induced immunity naturally wanes, adolescents and adults become important susceptible populations and potential sources of transmission. To address this, some WHO member states have already implemented booster immunization strategies with pertussis-containing vaccines for adolescents and adults, whereas China’s policy in this regard is still underdeveloped.^[150] With the upcoming availability of pertussis vaccines suitable for individuals aged >6 years in China, the implementation of adolescent pertussis-containing vaccination is expected to be promoted.

Currently, the adjusted immunization schedule in our country has advanced the first dose of pertussis vaccination to 2 months of age, with the aim of establishing an earlier immune barrier for infants and reducing the risk of early infection.^[94] However, infants aged 0–2 months remain in the immune protection gap before their own immunity is established. Maternal vaccination with pertussis-containing vaccines is considered an important strategy to bridge this gap and has been implemented internationally.^[151,152] So far, no vaccine specifically indicated for pregnant women has been approved for marketing in China. If China intends to promote maternal vaccination strategies, policy support and appropriate vaccine supply are needed, along with strengthened public education targeting pregnant women to improve vaccination compliance. Healthcare professionals should actively engage in pertussis prevention and control awareness campaigns through new media as well as traditional media, such as broadcast, television, and newspapers. They should promote public awareness of protective measures and guide the public to adopt good hygiene practices, such as proper mask-wearing, frequent handwashing, and cough etiquette.

4. Conclusion

In response to the ongoing challenge of pertussis reemergence in developed countries, Chinese experts launched the China Pertussis Initiative (CPI) in 2017, aligning with the Global Pertussis Initiative (GPI),^[3,9,10] and subsequently published the Expert Consensus on the China Pertussis Action Plan in 2021.^[4] In light of the high incidence of pertussis in recent years, China implemented a new immunization schedule for pertussis-containing vaccines starting in 2025, with the first dose advanced to 2 months of age to provide earlier immune protection for newborns. A booster dose was added at 6 years of age to provide more durable protection for school-aged children. These adjustments are expected to play a role in China’s future pertussis prevention and control efforts.

However, findings from domestic and international studies, together with practical experiences in addressing pertussis reemergence, remind us that the immune protection conferred by pertussis-containing vaccines is not sufficiently durable and that the shift in susceptible populations is ongoing. Attention should also be paid to the potential for antigenic variation of Bordetella pertussis to lead to immune escape, as well as to trends in antimicrobial resistance. Moreover, the atypical clinical presentation of pertussis in older age groups tends to be overlooked, allowing these individuals to serve as persistent sources of transmission. With pertussis reemergence remaining a challenge for the foreseeable future, achieving a life-course immunization strategy for pertussis—particularly maternal immunization—still requires considerable effort.

Under the new concepts and requirements of medical-preventive coordination and integration, healthcare professionals in China are now expected not only to standardize the diagnosis and treatment of vaccine-preventable infectious diseases but also to assume social responsibilities in public education and disease prevention. We expect that this consensus will provide healthcare professionals with essential knowledge and practical guidance and will, through the bidirectional integration of clinical care and public health services, contribute to the sustainable advancement and dynamic optimization of China’s pertussis prevention and control strategies.

Writing Experts

• Mei Zeng (Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China)

• Aiqiang Xu (Shandong Center for Disease Control and Prevention, Shandong Provincial Key Laboratory of Infectious Diseases, Shandong, China)

• Jiehao Cai (Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China)

• Yiping Chen (Department of Pediatric Infectious Diseases, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, China)

• Kaihu Yao (Laboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China)

• Yongsheng Xu (Department of Respiratory Medicine, Tianjin Children’s Hospital, Tianjin, China)

Core Consensus Working Group Experts

• Mei Zeng (Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China)

• Aiqiang Xu (Shandong Center for Disease Control and Prevention, Shandong Provincial Key Laboratory of Infectious Diseases, Shandong, China)

• Wenhong Zhang (Department of Infectious Diseases, Huashan Hospital, Fudan University, National Center for Infectious Diseases, Shanghai, China)

• Fu-Sheng Wang (Senior Department of Infectious Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China)

• Rongmeng Jiang (Beijing Ditan Hospital, Capital Medical University; National Center for Infectious Diseases; National/Beijing Quality Control Center for Infectious Diseases, Beijing, China)

• Kaihu Yao (Laboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China)

• Yiping Chen (Department of Pediatric Infectious Diseases, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, China)

• Yi Xu (Department of Infectious Diseases, Guangzhou Women and Children’s Medical Center, National Children’s Medical Center, Guangdong, China)

• Zhuoying Huang (Department of Immunization Program, Shanghai Center for Disease Control and Prevention, Shanghai, China)

• Xiaodong Sun (Shanghai Center for Disease Control and Prevention, Shanghai, China)

• Hui Zheng (Division of Bacterial Disease Vaccines, National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China)

• Zhujun Shao (National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China)

Consensus Reviewer Working Group (Listed in alphabetical order of surname pinyin)

• Jing Bi (Department of Infectious Diseases, Baoding Hospital of Beijing Children’s Hospital, Capital Medical University, Hebei, China)

• Biquan Chen (Department of Infectious Diseases, Anhui Children’s Hospital; Anhui Hospital, Children’s Hospital of Fudan University, Anhui, China)

• Mingliang Chen (Department of Laboratory Medicine, Minhang Hospital, Fudan University, Shanghai, China)

• Xing Chen (Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China)

• Yibing Cheng (Department of Pediatric Intensive Care, Henan Children’s Hospital, Henan, China)

• Huiling Deng (Xi’an Jiaotong University Affiliated Children’s Hospital, Xi’an Children’s Hospital, Shaanxi, China)

• Yanling Ge (Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China)

• Yingli He (Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China)

• Zhuoying Huang (Department of Immunization Program, Shanghai Center for Disease Control and Prevention, Shanghai, China)

• Daojiong Lin (Hainan Women and Children’s Medical Center; Department of Infectious Diseases, Hainan Branch, Children’s Hospital of Fudan University, Hainan, China)

• Xiaomei Liu (Kunming Children’s Hospital, Yunnan, China)

• Xiang Ma (Department of Respiratory Medicine, Children’s Hospital Affiliated to Shandong University, Shandong, China)

• Adong Shen (Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China; Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China)

• Zhujun Shao (National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China)

• Xiaodong Sun (Shanghai Center for Disease Control and Prevention, Shanghai, China)

• Jianmei Tian (Department of Infectious Diseases, Suzhou Children’s Hospital, Jiangsu, China)

• Ye Tian (Department of Infectious Diseases, Children’s Hospital of Nanjing Medical University, Jiangsu, China)

• Chaomin Wan (Department of Pediatric Infectious Diseases, West China Second University Hospital, West China Maternity and Children’s Hospital, Sichuan University, Sichuan, China)

• Dan Wu (Division of Bacterial Disease Vaccines, National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China)

• Hongmei Xu (Department of Infectious Diseases, Children’s Hospital of Chongqing Medical University, National Clinical Research Center, Chongqing, China)

• Yi Xu (Department of Infectious Diseases, Guangzhou Women and Children’s Medical Center, National Children’s Medical Center, Guangdong, China)

• Yongsheng Xu (Department of Respiratory Medicine, Tianjin Children’s Hospital, Tianjin, China)

• Hui Zheng (Division of Bacterial Disease Vaccines, National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China)

• Dongchi Zhao (Department of Pediatrics, Zhongnan Hospital of Wuhan University, Hubei, China)

• Hua Zhou (Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China)

• Yu Zhu (Department of Pediatric Infectious Diseases, West China Second University Hospital, West China Maternity and Children’s Hospital, Sichuan University, Sichuan, China)

• Zhiqiang Zhuo (Department of Infectious Diseases, Xiamen Children’s Hospital, Xiamen Hospital, Children’s Hospital of Fudan University, Fujian, China)

Academic Secretaries

• Jiehao Cai (Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China)

• Jingjing Li (Department of Infectious Diseases, Children’s Hospital of Fudan University, Shanghai, China)

Conflicts of Interest

None.