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. 2024 Oct 18;5(2):98–103. doi: 10.1097/ID9.0000000000000141

Interpretation of guidelines for diagnosis, management, and prevention of pertussis in China (version 2024)

Mei Zeng 1,*, Zhujun Shao 2, Jun Xia 3, Wenhong Zhang 4, Tianxing Feng 5, Jiehao Cai 1, Mingliang Chen 6
Editor: Wei Zhao
PMCID: PMC13277608  PMID: 42328621

Abstract

The resurgence of pertussis in China has recently attracted much attention. The incidence and burden of pertussis are largely underestimated in China owing to the lack of active pertussis surveillance and insufficient laboratory diagnosis. The high prevalence of macrolide-resistant Bordetella pertussis imposes a major challenge for the management of pertussis cases. To address a series of practice issues regarding pertussis diagnosis, treatment, and prevention, especially immunization practices, a multidisciplinary guideline development group (GDG) consisting of experts in the fields of infectious diseases, pediatric critical care medicine, clinical microbiology, epidemiology, and immunization planning jointly developed the first clinical practice guidelines for pertussis in China. Utilizing the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework recommended by the World Health Organization, the GDG formulated corresponding recommendations and suggestions. Good Practice Statements were created for issues not suitable for conventional evidence rating through the presentation of evidence and expert experience. The implementation suggestions for the 12 priority clinical questions given in this paper fully considered Chinese and international experiences as well as the national situation and policy. The primary target audience of these guidelines includes clinicians, microbiology laboratory staff, public health professionals, and policymakers.

Keywords: Whooping cough, Diagnosis, Management, Prophylaxis, Vaccination

1. Introduction

During the past decade, the resurgence of pertussis has been an emerging public health issue in China. In particular, the high prevalence of macrolide resistance in Bordetella pertussis (B. pertussis) in China makes antibiotic treatment difficult for young infants at high risk of severe pertussis. So far, the pertussis booster vaccination has not been introduced for school-aged children and adolescents. Misconceptions about the diphtheria, tetanus, acellular pertussis (DTaP) vaccination for children with underlying medical conditions remain among healthcare professionals and parents. In response to the current challenge of pertussis in China, a multidisciplinary guideline development group (GDG) comprising experts from multiple fields jointly developed new guidelines in 2024. The full methodology is detailed in the guidelines publication.[1] To help the target audience and related professionals understand the recommendations and implement the suggestions made in these guidelines, in this paper, we interpret the rationale for formulating the 12 recommendations and provide suggestions for their implementation.

2. Recommendations of the guidelines

Question 1: Which patients should be considered for laboratory diagnostic testing for pertussis?

Recommendation 1: Laboratory diagnostic testing for pertussis is recommended for suspected and clinically diagnosed cases of pertussis in a hospital setting where possible (Good Practice Statements (GPS)).

Implementation Suggestion: The GDG proposes the following criteria for suspected and clinically diagnosed cases. (1) Suspected cases should meet at least one of the following criteria: (i) any person with cough and at least one of the distinctive symptom triad of paroxysmal cough, inspiratory whooping, and posttussive vomiting; (ii) infants with either paroxysmal cough or apneic episodes and leukocytosis with a high percentage of lymphocytes; (iii) any person with a cough lasting for ≥2 weeks and absence of fever without other apparent cause. (2) Clinically diagnosed cases should meet at least one of the following criteria: (i) a suspected case having an epidemiological linkage with a laboratory-confirmed case of pertussis; (ii) any person with a cough lasting for ≥ 2 weeks and presenting with the three distinctive symptoms of pertussis; (iii) unvaccinated or incompletely vaccinated infants and toddlers with a cough of any duration and presenting with the three distinctive symptoms of pertussis and leukocytosis with a high percentage of lymphocytes.

Rationale for Recommendation: Early diagnosis enables the timely initiation of antimicrobial therapy to ameliorate symptoms, reduce the risk of pneumonia and death in infants, and decrease secondary transmission.[2,3 and 4] Accurate and timely laboratory diagnostic testing is essential for case management, reliable case reporting, and active surveillance.

Question 2: What laboratory tests should be used to diagnose pertussis?

Recommendation 2: Clinicians can use one of the following laboratory tests to diagnose pertussis: (1) isolation of B. pertussis from respiratory specimens; (2) detection of B. pertussis nucleic acid from respiratory specimens; (3) a single pertussis toxin (PT) immunoglobulin G (IgG) antibody level greater than the threshold cutoff indicative of acute pertussis infection but unsuitable for individuals vaccinated within the past year and for young infants; (4) a fourfold increase in PT-IgG titers in paired sera, suitable for a retrospective diagnosis (GPS).

Implementation Suggestion: Polymerase chain reaction (PCR) testing should be used as a routine diagnostic tool for laboratory confirmation of pertussis and preferentially introduced to the clinical laboratory in secondary and tertiary hospitals. Isolation of B. pertussis remains the gold standard for diagnosing pertussis and is an essential step for determining antimicrobial susceptibility. Serologic testing is of less value in clinical practice. The explanation of single-serum anti-PT IgG should consider factors such as the duration of pertussis, pertussis immunization history, and maternal antibodies.

Rationale for Recommendation: PCR assay, which is based on laboratory diagnostic standards validated by international reference laboratories[5,6 and 7] and domestic studies,[8,9 and 10] has the obvious advantages of easy and rapid operation and high sensitivity and specificity in diagnosing pertussis. Culture is a reliable and classic method for detecting B. pertussis and macrolide resistance, but it is less sensitive. Serologic testing cannot provide an early diagnosis because anti-PT IgG antibody is usually present 2 weeks after cough onset. Anti-PT IgG may be acquired through a maternally transmitted antibody, vaccine-induced antibody, or past infection.[5,6 and 7]

Question 3: What type of respiratory specimen should be collected for laboratory diagnostic testing of B. pertussis infection?

Recommendation 3: Both nasopharyngeal swabs and nasopharyngeal aspirates are recommended for use in the etiological diagnostic test for B. pertussis infection. Nasopharyngeal swabs are preferred over nasopharyngeal aspirates due to easy collection (GPS).

Implementation Suggestions: (1) For the nasopharyngeal swab, a polyester, rayon, or nylon flocked swab is recommended, consistent with World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (CDC) guidelines.[5,11] For doing culture, the swab should be placed in a Regan–Lowe transport medium stored at 2–8°C and transported to the laboratory within 24 hours after collection. If it is only used for PCR testing, the nasopharyngeal swab should be placed in a sterile container and stored at −20°C or below. (2) For the nasopharyngeal aspirate, a sample of at least 0.5 ml should be obtained aseptically.

Rationale for Recommendation: Previous studies have revealed an equivalent isolation rate of B. pertussis for both nasopharyngeal swabs and nasopharyngeal aspirates, higher than that for throat swabs.[12,13] U.S. CDC recommendations for the specimen storage temperature are adopted, which are in accordance with most research results.

Question 4: In the empirical treatment of pertussis, should azithromycin be the preferred option over erythromycin or clarithromycin?

Recommendation 4: The GDG preferentially suggests azithromycin over erythromycin and clarithromycin for the empirical treatment of pertussis (low certainty evidence, weak recommendation).

Implementation Suggestion: The preference for choosing azithromycin is premised on the high sensitivity of clinically isolated strains to macrolides. In China, the rate of resistance of macrolides to B. pertussis has reached 70–100%.[14,15] Empirical treatment should fully consider local trends of antimicrobial resistance in B. pertussis.

Rationale for Recommendation: The current body of evidence indicates the equivalent efficacy of azithromycin, erythromycin, and clarithromycin in the treatment of macrolide-sensitive B. pertussis infection.[16,17] Azithromycin offers some advantages, including short treatment duration, minimal risk of gastrointestinal adverse reactions, and good compliance with medication, and it is exclusively indicated for use in neonates. In addition, parents and children prefer to accept azithromycin therapy.

Question 5: What antibacterial agent should be used for people with pertussis caused by macrolide-resistant B. pertussis or failing to respond to macrolide treatment?

Recommendation 5: For pertussis caused by macrolide-resistance B. pertussis or failing to respond to empirical macrolide treatment, (1) Trimethoprim/sulfamethoxazole is recommended for use in children aged ≥2 months and adults (low certainty evidence, strong recommendation). Cefoperazone/sulbactam or piperacillin/tazobactam can be considered for use in infants aged <2 months.[18] (2) Levofloxacin can be considered as an alternative option for adults with pertussis (very low certainty evidence, conditional recommendation).

Implementation Suggestion: Trimethoprim/sulfamethoxazole should not be prescribed to infants younger than 2 months and women during pregnancy or breastfeeding unless no alternative drug is available.[19] Patients should be informed of adverse reactions to trimethoprim/sulfamethoxazole and monitored during treatment. Given the high prevalence of macrolide-resistant B. pertussis in China, trimethoprim/sulfamethoxazole can be used as the first-line choice for the empirical treatment of pertussis in individuals ≥ 2 months.

Rationale for Recommendation: Trimethoprim/sulfamethoxazole is as effective as erythromycin in terms of treatment efficacy and bacterial clearance for pertussis.[20,21] Currently, clinical isolates of B. pertussis in China have displayed high resistance to macrolides but remain sensitive to trimethoprim/sulfamethoxazole.[22,23,24 and 25] The B. pertussis isolates recovered from Chinese children exhibited similar 90% minimum inhibitory concentration (MIC90) values for sulfamethoxazole/trimethoprim (0.3 mg/L) and for levofloxacin (0.5 mg/L), lower MIC90 value for piperacillin (<0.016 mg/L), cefoperazone/sulbactam (0.047 mg/L), ampicillin/sulbactam (0.19 mg/L), ceftazidime (0.19 mg/L), and ceftriaxone (0.094–0.190 mg/L), potentially suggesting these antibiotics are in vitro sensitivity.[23,24 and 25] Two observational studies from China indicated that piperacillin/tazobactam and cefoperazone/sulbactam were more effective than erythromycin and azithromycin in treating young children infected with macrolide-resistant B. pertussis, especially in bacteria clearance.[23,24] For adult patients, levofloxacin can be considered as an alternative drug, as the in vitro MIC90 for levofloxacin is similar to that for trimethoprim/sulfamethoxazole; however, the in vivo efficacy needs to be evaluated. Future high-quality research is required to address the research gap in this priority clinical issue in China.

Question 6: Should leukodepletion (exchange blood transfusion or leukapheresis) be recommended for children with severe pertussis with hyperleukocytosis?

Recommendation 6: The GDG suggests the adoption of leukodepletion as a last-resort therapeutic approach to treat young children with critically severe pertussis with hyperleukocytosis. For severe infant cases of pertussis, leukodepletion can be considered if the total leukocyte count rapidly reaches ≥50 × 109/L or the leukocyte count is ≥30 × 109/L with a rapid rise of ≥50% within 24 hours, resulting in pulmonary hypertension or cardiac and lung dysfunction (very low certainty evidence, conditional recommendation).

Implementation Suggestion: The timely initiation of leukodepletion may yield benefits in the early stage of pulmonary hypertension and in the compensatory phase of cardiopulmonary dysfunction. The adoption of leukodepletion requires the professional skills of healthcare personnel and careful consideration of the equipment at local medical institutions.

Rationale for Recommendation: Leukocytosis (leukocyte count ≥30 × 109/L) is a risk factor associated with severe pertussis and fatal outcomes in infants.[26,27] The mortality risk was 32.1% in severe pertussis patients (aged 15 days to 17 months) with hyperleukocytosis (leukocyte count: 45 × 109 to 135.4 × 109/L) undergoing leukodepletion.[28] Two observational studies suggested a slightly increased risk of death in the leukodepletion group compared with the non-leukodepletion group (n = 97, rate difference = 0.26, 95% CI: 0.06–0.46).[29,30] Overall, the GDG is uncertain about the therapeutic effect of leukodepletion.

Question 7: Should people with pertussis be treated with systemic corticosteroid?

Recommendation 7: A short course of systemic corticosteroid use is suggested as an adjuvant treatment of typical pertussis in patients during the stage of paroxysmal cough or in patients with recurrent attacks of asphyxia (low certainty evidence, conditional recommendation).

Implementation Suggestions: (1) The duration of systemic steroid treatment should not exceed 7 to 10 days, with an equivalent dosage of prednisone ranging from 0.5 to 2 mg·kg-1·d-1 and a maximum dosage of 40 mg/day. (2) Systemic steroid treatment is not recommended for patients with severe hyperleukocytosis (leukocyte count ≥50 × 109/L or a white blood cell (WBC) count of ≥30 × 109/L with a progressive elevation of >50% within 24 hours).[31] Nebulized steroid inhalation can be used.

Rationale for Recommendation: Two cohort studies indicated the beneficial effect of systemic steroid treatment for reducing paroxysmal cough attacks, asphyxia attacks, and whooping duration in hospitalized children with pertussis, especially in infants.[32,33] An observational study reported the resolution of apnea within 24 hours of steroid inhalation and improvement of cough after 72 hours of steroid inhalation.[34]

Question 8: Should people exposed to pertussis receive post-exposure chemoprophylaxis?

Recommendation 8: The GDG suggests post-exposure chemoprophylaxis for close contacts to prevent secondary transmission of pertussis in the following scenarios: (1) household contacts; (2) partially vaccinated or unvaccinated infants; (3) incompletely vaccinated young children attending nurseries and kindergartens; (4) hospital staff taking care of infants under 3 months old and staff working in neonatal care facilities; (5) staff working in nurseries and kindergartens; (6) people exposed in the context of a pertussis outbreak or cluster (low certainty evidence, conditional recommendation).

Implementation Suggestions: (1) Antibiotic chemoprophylaxis should be started as soon as possible, within 21 days and ideally within 7 days of exposure.[35] (2) The drug selection, dosage, and duration for chemoprophylaxis are the same as in the treatment regimen for pertussis.[36] Trimethoprim/sulfamethoxazole is the preferred drug for chemoprophylaxis in children aged ≥2 months and adults. For exposed infants <2 months old or those with contraindications to sulfonamides, drug prophylaxis should be in accordance with advice from infectious disease specialists.

Rationale for Recommendation: RCT studies have suggested that the risk of developing laboratory-confirmed pertussis may be reduced by 33% in household contacts treated with erythromycin prophylaxis.[37,38] A retrospective study indicated 43.9% effectiveness (95% CI: −1.8–69.1%) for preventing household secondary PCR/culture-confirmed pertussis and 82.3% effectiveness (95% CI: 39.1–94.9%) for contacts treated within 7 days of exposure.[35] An RCT study found that the absolute risk reduction of secondary asymptomatic infection was only 6.7% among vaccinated healthcare workers within the past 4 years.[39] Despite the low certainty of the evidence, the GDG recommends individualized chemoprophylaxis in certain groups to reduce secondary infection, protect susceptible children and infants at high risk of severe pertussis, and confine the size of outbreaks.

Question 9: Should infants start immunization with pertussis-containing vaccine at 2 months of age?

Recommendation 9: The GDG suggests the first dose of a pertussis-containing vaccine be administered to infants at 2 months of age (low certainty evidence, conditional recommendation).

Implementation Suggestion: In China, pertussis-containing vaccines include the free DTaP vaccine and the self-paid diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type b (DTaP-IPV/Hib) vaccines and DTaP/Hibvaccines. Only the DTaP-IPV/Hib vaccine is approved for use in infants at 2 months of age. Administration of a DTaP-containing vaccine at the age of 2 months should consider the parents’ willingness.

Rationale for Recommendation: Administration of pertussis-containing vaccines at 2 and 3 months of age has equivalent immunogenicity and safety.[40,41] In China, where newborns lack protective antibodies against pertussis,[42,43 and 44] starting vaccination at 2 months can provide earlier protection for high-risk infants under 3 months.[45] A WHO position paper recommends that every country initiates pertussis vaccination at 6 weeks and no later than 8 weeks of age.[46] Timely vaccination, especially starting from 2 months of age, substantially reduces the burden of infant pertussis.[47]

Question 10: Should one booster dose of DTaP vaccine be recommended for preschool children in China?

Recommendation 10: The GDG recommends an additional booster dose of DTaP vaccine be administered to preschool children aged 4 to 6 years (moderate certainty evidence, strong recommendation).

Implementation Suggestion: It is an urgent necessity to promote the implementation of the DTaP booster vaccination for preschool children in China.

Rationale for Recommendation: Seroepidemiological studies from China revealed that anti-PT IgG titers declined to a nadir (3.72 U/ml) at age 6 and then increased, reaching a peak at age 9.[48] WHO recommends the administration of an additional booster dose of pertussis vaccine at school entry.[46] International studies demonstrated that preschool booster vaccination significantly reduced disease burden.[49] Previous studies have proven the safety and efficacy of DTaP vaccination for preschool children.[50,51 and 52]

Question 11: Should premature infants receive the first dose of pertussis-containing vaccine according to chronological age?

Recommendation 11: The GDG suggests the first dose of pertussis-containing vaccine be administered to premature infants in accordance with their chronological age (low certainty evidence, conditional recommendation).

Implementation Suggestion: Vaccinating preterm infants can start when babies are clinically stable or upon hospital discharge.[53]

Rationale for Recommendation: Preterm infants are more susceptible to pertussis than full-term infants due to fewer protective antibodies from their mothers,[54] and they are at higher risk of severe complications requiring respiratory support, and death.[27,55] Preterm infants respond to pertussis vaccines similarly to full-term infants, with comparable effectiveness and side effects.[56]

Question 12: Should children with neurological diseases receive pertussis-containing vaccines routinely?

Recommendation 12: The GDG recommends pertussis-containing vaccines be administered to children with neurological diseases when their condition is stable or in the recovery phase (GPS).

Implementation Suggestions: (1) For children with progressive or unstable neurological diseases, pertussis vaccination should be deferred until their condition stabilizes. (2) For children with a hypotonic–hyporesponsive episode within 48 hours, a seizure within 3 days, or a family history of seizures following previous pertussis-containing vaccines, subsequent doses of pertussis vaccine can continue to be administered.

Rationale for Recommendation: No causal link between DTaP vaccination and neurological diseases has been demonstrated.[57] Existing evidence and surveillance data support the administration of acellular pertussis vaccines to children with various neurological conditions.[58]

3. Conclusion

These practice guidelines enhance transparency in the guideline development process, aiming to enhance their practical applicability for relevant healthcare providers and public health professionals. Although some recommendations lack the support of high-quality evidence, the GDG has taken this factor into consideration as much as possible and formulated reasonable and implementable recommendations based on Chinese realities and expert experience. The international successful experience of controlling pertussis resurgence through the optimization of immunization strategies underscores the need for more research evidence from China to provide policy support.

Author Contributions

Mei Zeng, Jun Xia, Tianxing Feng, Jiehao Cai, Mingliang Chen wrote the paper. Mei Zeng, Zhujun Shao, Wenhong Zhang conceived the guideline. Jun Xia, Mei Zeng and Tianxing Feng participated in the evidence summary. All authors read and approved the final manuscript.

Conflicts of Interest

None.

Funding Statement

This work is supported by the Shanghai Municipal Sixth Round Three-Year Action Plan for Strengthening the Construction of the Public Health System (GWVI-2.1.2).

Footnotes

How to cite this article: Zeng M, Shao ZJ, Xia J, et al. Interpretation of guidelines for diagnosis, management, and prevention of pertussis in China (2024 edition). Infect Dis Immun 2025;5(2):98–103. doi: 10.1097/ID9.0000000000000141

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