Asymptomatic Bordetella pertussis infections in a longitudinal cohort of young African infants and their mothers

Recent pertussis resurgence in numerous countries may be driven by asymptomatic infections. Most pertussis surveillance studies are cross-sectional and cannot distinguish asymptomatic from pre-symptomatic infections. Longitudinal surveillance could overcome this barrier, providing more information about the true burden of pertussis at the population level. Here we analyze 17,442 nasopharyngeal samples from a longitudinal cohort of 1320 Zambian mother/infant pairs. Our analysis has two elements. First, we demonstrate that the full range of IS481 qPCR CT values provides insight into pertussis epidemiology, showing concordance of low and high CT results over time, within mother/infant pairs, and in relation to symptomatology. Second, we exploit these full-range qPCR data to demonstrate a high incidence of asymptomatic pertussis, including among infants. Our results demonstrate a wider burden of pertussis infection than we anticipated in this population, and expose key limitations of threshold-based interpretation of qPCR results in infectious disease surveillance.

[1]  P. Rohani,et al.  Implementation and adherence of routine pertussis vaccination (DTP) in a low-resource urban birth cohort , 2020, BMJ Open.

[2]  N. Grassly,et al.  A pilot study on use of live attenuated rotavirus vaccine (Rotarix™) as an infection challenge model. , 2020, Vaccine.

[3]  N. Lennon,et al.  Estimating epidemiologic dynamics from cross-sectional viral load distributions , 2020, medRxiv.

[4]  A. Charlett,et al.  Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[5]  K. O'Brien,et al.  Pneumococcal colonization prevalence and density among Thai children with severe pneumonia and community controls , 2020, PloS one.

[6]  Young-In Kim,et al.  A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein , 2019, Antimicrobial Agents and Chemotherapy.

[7]  Young-In Kim,et al.  A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein , 2019, Antimicrobial Agents and Chemotherapy.

[8]  A. Vaughan,et al.  Controlled Human Infection With Bordetella pertussis Induces Asymptomatic, Immunizing Colonization , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  Jingcheng Yang,et al.  Commensal Microbes Affect Host Humoral Immunity to Bordetella pertussis Infection , 2019, Infection and Immunity.

[10]  N. Mistry,et al.  Detection of Mycobacterium tuberculosis RNA in bioaerosols from pulmonary tuberculosis patients. , 2019, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[11]  S. Scarpino,et al.  Introduction to pertussis transmission and epidemiological dynamics , 2018, Pertussis.

[12]  S. Scarpino,et al.  Epilogue: The road ahead , 2018 .

[13]  D. Ghosh,et al.  Quantifying the infectiousness of post-kala-azar dermal leishmaniasis towards sandflies , 2019 .

[14]  D. Sano,et al.  A review on recent progress in the detection methods and prevalence of human enteric viruses in water. , 2018, Water research.

[15]  P. Dubey,et al.  Hyperbiofilm Formation by Bordetella pertussis Strains Correlates with Enhanced Virulence Traits , 2017, Infection and Immunity.

[16]  E. Nelson,et al.  An update of the global burden of pertussis in children younger than 5 years: a modelling study. , 2017, The Lancet. Infectious diseases.

[17]  P. Rohani,et al.  The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis , 2017, F1000Research.

[18]  S. Madhi,et al.  Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  A. Tozzi,et al.  Parents as source of pertussis transmission in hospitalized young infants , 2017, Infection.

[20]  D. Litt,et al.  Survey of Household Contacts of Infants With Laboratory-confirmed Pertussis Infection During a National Pertussis Outbreak in England and Wales , 2017, The Pediatric infectious disease journal.

[21]  C. Gill,et al.  Incidence of Severe and Nonsevere Pertussis Among HIV-Exposed and -Unexposed Zambian Infants Through 14 Weeks of Age: Results From the Southern Africa Mother Infant Pertussis Study (SAMIPS), a Longitudinal Birth Cohort Study , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  S. Glazer,et al.  The potential role of subclinical Bordetella Pertussis colonization in the etiology of multiple sclerosis. , 2016, Immunobiology.

[23]  A. King,et al.  The pertussis enigma: reconciling epidemiology, immunology and evolution , 2016, Proceedings of the Royal Society B: Biological Sciences.

[24]  C. Kenyon,et al.  Sources of Infant Pertussis Infection in the United States , 2015, Pediatrics.

[25]  B. Althouse,et al.  Asymptomatic transmission and the resurgence of Bordetella pertussis , 2015, BMC Medicine.

[26]  R. Cunney,et al.  Pertussis in young infants: clinical presentation, course and prevention. , 2014, Irish medical journal.

[27]  O. Soetens,et al.  PREVALENCE OF BORDETELLA HOLMESII AND BORDETELLA BRONCHISEPTICA IN RESPIRATORY TRACT SAMPLES FROM BELGIAN PATIENTS WITH PERTUSSIS-LIKE SYMPTOMS BY SENSITIVE CULTURE METHOD AND MASS SPECTROMETRY , 2013, Acta clinica Belgica.

[28]  J. Cherry Pertussis: Challenges Today and for the Future , 2013, PLoS pathogens.

[29]  P. Rohani,et al.  Perplexities of pertussis: recent global epidemiological trends and their potential causes , 2013, Epidemiology and Infection.

[30]  K. Macartney,et al.  Sources of pertussis infection in young infants: a review of key evidence informing targeting of the cocoon strategy. , 2013, Vaccine.

[31]  T. Clark,et al.  Pertussis Pseudo-outbreak Linked to Specimens Contaminated by Bordetella pertussis DNA From Clinic Surfaces , 2012, Pediatrics.

[32]  M. Tondella,et al.  Novel Multitarget Real-Time PCR Assay for Rapid Detection of Bordetella Species in Clinical Specimens , 2011, Journal of Clinical Microbiology.

[33]  J. Drake,et al.  The decline and resurgence of pertussis in the US. , 2011, Epidemics.

[34]  Benjamin J Cowling,et al.  Viral Shedding and Clinical Illness in Naturally Acquired Influenza Virus Infections , 2010, The Journal of infectious diseases.

[35]  D. Armangil,et al.  Maternal pertussis is hazardous for a newborn: a case report. , 2010, The Turkish journal of pediatrics.

[36]  U. Heininger Update on pertussis in children , 2010, Expert review of anti-infective therapy.

[37]  H. Sung,et al.  Comparative evaluation of two automated systems for nucleic acid extraction of BK virus: NucliSens easyMAG versus BioRobot MDx. , 2009, Journal of virological methods.

[38]  N. Manca,et al.  Performance evaluation of the automated NucliSens easyMAG nucleic acid extraction platform in comparison with QIAamp Mini kit from clinical specimens. , 2009, Diagnostic microbiology and infectious disease.

[39]  Nicholas Wood,et al.  Pertussis in early infancy: disease burden and preventive strategies , 2009, Current opinion in infectious diseases.

[40]  K. V. Van Horn,et al.  Comparison of 3 swab transport systems for direct release and recovery of aerobic and anaerobic bacteria. , 2008, Diagnostic microbiology and infectious disease.

[41]  J. Mertsola,et al.  Factors contributing to pertussis resurgence. , 2008, Future microbiology.

[42]  M. Tondella,et al.  Real-Time Polymerase Chain Reaction Detection of Bordetella pertussis DNA in Acellular Pertussis Vaccines , 2008, The Pediatric infectious disease journal.

[43]  M. Struelens,et al.  A specific real-time PCR assay for the detection of Bordetella pertussis. , 2007, Journal of medical microbiology.

[44]  W. Butt,et al.  Pertussis: Severe clinical presentation in pediatric intensive care and its relation to outcome* , 2007, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[45]  J. Englund,et al.  Multitarget PCR for Diagnosis of Pertussis and Its Clinical Implications , 2006, Journal of Clinical Microbiology.

[46]  R. Clover,et al.  Pertussis infection in the United States: role for vaccination of adolescents and adults. , 2006, Journal of the American Board of Family Medicine : JABFM.

[47]  K. Register,et al.  Prevalence and Sequence Variants of IS481 in Bordetella bronchiseptica: Implications for IS481-Based Detection of Bordetella pertussis , 2006, Journal of Clinical Microbiology.

[48]  J. Schellekens,et al.  Pertussis Sources of Infection and Routes of Transmission in the Vaccination Era , 2005, The Pediatric infectious disease journal.

[49]  Evelinda Trindade,et al.  Epidemiology of pertussis. , 2005, The Pediatric infectious disease journal.

[50]  K. Ehresmann,et al.  Infant Pertussis: Who Was the Source? , 2004, The Pediatric infectious disease journal.

[51]  L. Ravà,et al.  Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life. , 2003, Pediatrics.

[52]  M Elizabeth Halloran,et al.  Effects of pertussis vaccination on disease: vaccine efficacy in reducing clinical severity. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[53]  S. Halperin,et al.  Pertussis of adults and infants. , 2002, The Lancet. Infectious diseases.

[54]  A. Golaz,et al.  Issues Associated with and Recommendations for Using PCR To Detect Outbreaks of Pertussis , 2002, Journal of Clinical Microbiology.

[55]  M. Loeffelholz,et al.  Real-Time PCR Assay Targeting IS481of Bordetella pertussis and Molecular Basis for Detecting Bordetella holmesii , 2001, Journal of Clinical Microbiology.

[56]  J. Deen,et al.  Household contact study of Bordetella pertussis infections. , 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[57]  N. M. Sirota,et al.  Outbreak of Pertussis in a Fully Immunized Adolescent and Adult Population , 1994 .

[58]  S. Long,et al.  Widespread silent transmission of pertussis in families: antibody correlates of infection and symptomatology. , 1990, The Journal of infectious diseases.

[59]  O. Sjaastad Epilogue , 1891, The Hospital.

[60]  H. D. de Melker,et al.  Asymptomatic infection and transmission of pertussis in households: a systematic review. , 2019, Clinical Infectious Diseases.

[61]  W. Heisenberg,et al.  Psoriasis - a review of recent progress, characteristics, diagnostic management , 2022, Journal of Education, Health and Sport.