High Burden of Viral Respiratory Co-infections in a Cohort of Children with Suspected Pulmonary Tuberculosis

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2020 Dec 5

PMID 33276721

Citations 6

Authors

M M van der Zalm

E Walters

M Claassen

M Palmer

J A Seddon

A M Demers

M L Shaw

E D McCollum

G U Van Zyl

A C Hesseling

Affiliations

Soon will be listed here.

Abstract

Background: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up.

Methods: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8.

Results: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8.

Conclusions: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.

Citing Articles

Anthony M, Johnson L, van Niekerk M, Mfwaze A, Bavuma B, Hesseling A IJTLD Open. 2024; 1(11):495-500.

PMID: 39544879 PMC: 11558787. DOI: 10.5588/ijtldopen.24.0355.

SARS-CoV-2 coinfection in children with severe airway obstruction due to pulmonary tuberculosis.

Goussard P, van Wyk L, Venkatakrishna S, Rabie H, Schubert P, Frigati L Pediatr Pulmonol. 2024; 59(12):3446-3456.

PMID: 39185631 PMC: 11601029. DOI: 10.1002/ppul.27232.

Respiratory adenovirus infections in children: a focus on Africa.

van der Zalm M, Sam-Agudu N, Verhagen L Curr Opin Pediatr. 2024; 36(3):342-348.

PMID: 38465727 PMC: 11062604. DOI: 10.1097/MOP.0000000000001335.

and SARS-CoV-2 co-infections: The knowns and unknowns.

Chiok K, Dhar N, Banerjee A iScience. 2023; 26(5):106629.

PMID: 37091987 PMC: 10082467. DOI: 10.1016/j.isci.2023.106629.

Transcriptomics for child and adolescent tuberculosis.

Kaforou M, Broderick C, Vito O, Levin M, Scriba T, Seddon J Immunol Rev. 2022; 309(1):97-122.

PMID: 35818983 PMC: 9540430. DOI: 10.1111/imr.13116.

References

Papadopoulos N, Bates P, Bardin P, Papi A, Leir S, Fraenkel D . Rhinoviruses infect the lower airways. J Infect Dis. 2000; 181(6):1875-84. DOI: 10.1086/315513. View

Self W, Williams D, Zhu Y, Ampofo K, Pavia A, Chappell J . Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia. J Infect Dis. 2015; 213(4):584-91. PMC: 4721902. DOI: 10.1093/infdis/jiv323. View

van der Zalm M, Uiterwaal C, Wilbrink B, de Jong B, Verheij T, Kimpen J . Respiratory pathogens in respiratory tract illnesses during the first year of life: a birth cohort study. Pediatr Infect Dis J. 2009; 28(6):472-6. DOI: 10.1097/inf.0b013e318195e26e. View

Dangor Z, Izu A, Moore D, Nunes M, Solomon F, Beylis N . Temporal association in hospitalizations for tuberculosis, invasive pneumococcal disease and influenza virus illness in South African children. PLoS One. 2014; 9(3):e91464. PMC: 3950213. DOI: 10.1371/journal.pone.0091464. View

McNamee L, Harmsen A . Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection. Infect Immun. 2006; 74(12):6707-21. PMC: 1698099. DOI: 10.1128/IAI.00789-06. View

Man W, van Houten M, Merelle M, Vlieger A, Chu M, Jansen N . Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study. Lancet Respir Med. 2019; 7(5):417-426. PMC: 7172745. DOI: 10.1016/S2213-2600(18)30449-1. View

Dube F, Kaba M, Robberts F, Tow L, Lubbe S, Zar H . Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa. BMC Infect Dis. 2016; 16(1):597. PMC: 5075757. DOI: 10.1186/s12879-016-1934-z. View

Hong J, Lee H, Piedra P, Choi E, Park K, Koh Y . Lower respiratory tract infections due to adenovirus in hospitalized Korean children: epidemiology, clinical features, and prognosis. Clin Infect Dis. 2001; 32(10):1423-9. DOI: 10.1086/320146. View

DENNY Jr F . The clinical impact of human respiratory virus infections. Am J Respir Crit Care Med. 1995; 152(4 Pt 2):S4-12. DOI: 10.1164/ajrccm/152.4_Pt_2.S4. View

10.

Walaza S, Tempia S, Dawood H, Variava E, Wolter N, Dreyer A . The Impact of Influenza and Tuberculosis Interaction on Mortality Among Individuals Aged ≥15 Years Hospitalized With Severe Respiratory Illness in South Africa, 2010-2016. Open Forum Infect Dis. 2019; 6(3):ofz020. PMC: 6424478. DOI: 10.1093/ofid/ofz020. View

11.

Dijkema J, Van Ewijk B, Wilbrink B, Wolfs T, Kimpen J, van der Ent C . Frequency and Duration of Rhinovirus Infections in Children With Cystic Fibrosis and Healthy Controls: A Longitudinal Cohort Study. Pediatr Infect Dis J. 2015; 35(4):379-83. DOI: 10.1097/INF.0000000000001014. View

12.

Marais B, Gie R, Schaaf H, Starke J, Hesseling A, Donald P . A proposed radiological classification of childhood intra-thoracic tuberculosis. Pediatr Radiol. 2004; 34(11):886-94. DOI: 10.1007/s00247-004-1238-0. View

13.

Aberle J, Aberle S, Pracher E, Hutter H, Kundi M, Popow-Kraupp T . Single versus dual respiratory virus infections in hospitalized infants: impact on clinical course of disease and interferon-gamma response. Pediatr Infect Dis J. 2005; 24(7):605-10. DOI: 10.1097/01.inf.0000168741.59747.2d. View

14.

Marais B, Gie R, Hesseling A, Schaaf H, Lombard C, Enarson D . A refined symptom-based approach to diagnose pulmonary tuberculosis in children. Pediatrics. 2006; 118(5):e1350-9. DOI: 10.1542/peds.2006-0519. View

15.

Kamau E, Onyango C, Otieno G, Kiyuka P, Agoti C, Medley G . An Intensive, Active Surveillance Reveals Continuous Invasion and High Diversity of Rhinovirus in Households. J Infect Dis. 2018; 219(7):1049-1057. PMC: 6420174. DOI: 10.1093/infdis/jiy621. View

16.

Regamey N, Kaiser L, Roiha H, Deffernez C, Kuehni C, Latzin P . Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study. Pediatr Infect Dis J. 2008; 27(2):100-5. DOI: 10.1097/INF.0b013e31815922c8. View

17.

Makela M, Puhakka T, Ruuskanen O, Leinonen M, Saikku P, Kimpimaki M . Viruses and bacteria in the etiology of the common cold. J Clin Microbiol. 1998; 36(2):539-42. PMC: 104573. DOI: 10.1128/JCM.36.2.539-542.1998. View

18.

Zar H, Ferkol T . The global burden of respiratory disease-impact on child health. Pediatr Pulmonol. 2014; 49(5):430-4. DOI: 10.1002/ppul.23030. View

19.

Dodd P, Yuen C, Sismanidis C, Seddon J, Jenkins H . The global burden of tuberculosis mortality in children: a mathematical modelling study. Lancet Glob Health. 2017; 5(9):e898-e906. PMC: 5556253. DOI: 10.1016/S2214-109X(17)30289-9. View

20.

Edmond K, Scott S, Korczak V, Ward C, Sanderson C, Theodoratou E . Long term sequelae from childhood pneumonia; systematic review and meta-analysis. PLoS One. 2012; 7(2):e31239. PMC: 3285155. DOI: 10.1371/journal.pone.0031239. View