Chlamydia trachomatis infection influences the clinical course of acute bronchiolitis

Abstract

The frequency of Chlamydia trachomatis infection among young infants admitted with acute bronchiolitis was analysed to determine whether the former affects the clinical course of the latter. A total of 92 infants aged <6 months admitted with acute bronchiolitis were tested for C. trachomatis by a cell culture technique, obtaining nasal smears from each infant’s nostrils. A second nasal sampling was taken for respiratory viruses from the study group and tested with real-time polymerase chain reaction. Clinical characteristics of C. trachomatis-positive and -negative cases were compared. C. trachomatis was detected in 22.8% of the infants, mostly as coinfection with respiratory viral agents. Infection with C. trachomatis affected the clinical outcome in acute bronchiolitis and such infants tended to have severe bronchiolitis.

Keywords

Chlamydia trachomatis infant acute bronchiolitis respiratory viruses clinical outcome

Introduction

Chlamydia trachomatis is a small atypical bacterial pathogen transmitted by women to their newborn babies during vaginal delivery when cervicovaginal secretion are thus infected. Such neonates may develop conjunctivitis and afebrile pneumonia may be seen in infants aged 1–3 months. C. trachomatis may also cause nasopharyngitis and otitis media.¹ Approximately 11–20% of infants born to infected mothers develop symptomatic C. trachomatis pneumonia before the age of two months.² Half of these present with conjunctivitis and middle ear abnormality. In clinical practice, nasal obstruction, discharge, cough and tachypnoea are frequent. On admission, most infants are afebrile, with scattered crackles but no wheezing on chest auscultation.³

Acute bronchiolitis (AB) is the most common acute lower respiratory system disease in infants and is often caused by viral infection. Respiratory syncytial virus (RSV) is the commonest cause (50–80%), but other viruses have also been implicated as sole pathogens or as coinfections with or without RSV.^4,5

Although the association of viral and bacterial co-infection in the lower respiratory tract has been known for long, C. trachomatis as an atypical bacterial pathogen as single or co-pathogen in infants admitted with AB accompanied by wheezing is a relatively recent discovery.^6–8 However, the clinical significance of such an association has not yet been clearly defined.

The aim of our prospective study was to assess the frequency of C. trachomatis, confirmed by cell culture, among infants admitted with AB and to describe their clinical features and laboratory results, and, in particular, to assess their clinical course.

Materials and Methods

Our study of children admitted with AB was conducted between October 2015 and October 2016 at the General Pediatrics ward of the Children’s Hospital, Ege University, Turkey, a tertiary care paediatric teaching hospital. The Ethics Committee of the University approved the study (Reg. no. E.155326). AB was defined as an acute lower respiratory illness characterised by cough alongside wheezing (an audible whistling sound from the chest on breathing) or crackles (a sound likened to opening ‘velcro’ on chest auscultation). Detailed demographic and epidemiological data were recorded on admission, and during admission, clinical and laboratory data were obtained from each infant using a standardised form. Infants were recruited with informed, written, parental consent. Previously healthy infants aged <6 months with their first attack of AB were enrolled. Those who had developed nosocomial AB after being admitted or had a known history of bronchopulmonary dysplasia or chronic heart disease were excluded.

On hospital admission, the severity score of acute bronchiolitis previously described by Wang et al.⁹ was used for each infant. This score is based on parameters including respiratory rate, retractions, wheeze and general appearance. Each parameter was given points in the range of 0–3 and then the child’s points were added up to describe the severity of AB; 0–3 points showed mild bronchiolitis, 4–8 points moderate bronchiolitis, and 9–12 points indicated severe bronchiolitis. Initial examination documented the presence or absence of wheezing. Laboratory variables measured were leucocyte count, percentage of eosinophils and C-reactive protein (CRP) levels. Individuals were divided into two groups according to positive or negative results for C. trachomatis and compared.

A nasal smear was obtained from each infant’s nostrils and inserted into two separate tubes—with viral transport media (Vircell, Spain)—within 24 h of admission. The first tube was tested for RSV, influenza virus type A and B (Inf-A, Inf-B), adenovirus (Ad), parainfluenza viruses (PıV types 1-4), human rhinovirus (HrV), human coronavirus (HCoV), human metapneumovirus (HmpV) and human bocavirus (HBoV) using real-time multiplex polymerase chain reaction (PCR) methods (RealAccurate®, Respiratory RT PCR, PathoFinder, Netherlands and Seeplex® RV15 ACE Detection, Seegene, South Korea). The second tube was immediately sent for cell culture to detect C. trachomatis, whose isolation was achieved by shell vial assay using a McCoy cell line. Coverslips and slides were stained with a fluorescent isothiocynate labelled monoclonal antibody specific for C. trachomatis (Light Diagnostics, Chemicon International, USA) according to the manufacturer’s protocol. Coverslips were examined for typical fluorescent inclusion bodies and were considered positive if one or more such were present.

Statistical analyses were performed using SPSS version 21.0 for personal computers (Chicago, IL, USA). We used Fisher’s exact test and Pearson χ² test for categorical data. For continuous data, the Shapiro–Wilk test was used to determine whether data are normally distributed and Mann–Whitney U test was used for pair-wise comparison if the group differences were not found normally distributed. A value of P < 0.05 was considered statistically significant.

Results

A total of 92 previously healthy infants were accepted in to our study (mean age = 2.9 ± 1.6 months, 51.1% male). At least one viral respiratory agent was found in 78 (84.8%), the most common being RSV (n = 51, 55.4%) followed by HrV (n = 38, 41.3%), Ad (n = 7, 7.6%), PıV and HboV (n = 5 each, 5.4%), Inf A or B, HmpV and HCo (n = 3 each, 3.2%). C. trachomatis was detected in 21/92 (22.8%), of whom 17 (80.9%) had co-infection with other respiratory viral agents detected. Only four (19%) had C. trachomatis as a sole pathogen (Table 1).

Table 1.

Viral respiratory agents of C. trachomatis-positive and -negative infants with acute bronchiolitis (n = 92).

	C. trachomatis- positive (n = 21)	C. trachomatis- negative (n = 71)
Respiratory syncytial virus	11 (52.4)	40 (56.4)
Rhinovirus	5 (23.8)	14 (19.7)
Parainfluenza virus	1 (4.8)	4 (5.6)
Influenza virus	–	3 (4.2)
Adenovirus	1 (4.8)	5 (7.1)
Human bocavirus	1 (4.8)	1 (1.4)
Human metapneumovirus	–	3 (4.2)
Human coronovirus	2 (9.4)	1 (1.4)

Values are presented as n (%).

C. trachomatis, Chlamydia trachomatis.

Table 2 shows the demographic characteristics of the two groups, positive or negative for C. trachomatis. More than half the infants accepted in our study presented with moderate bronchiolitis. There was no significant difference in gender and age, but significant differences are tabulated in Table 2. Wheezing on admission was significantly more frequent in the positive group than the negative (81% vs. 19%, respectively, P = 0.01). The presence of crackles was found only in 19% (4/21) of positive infants compared with 36.6% (26/71) of negative infants. The mean respiratory rate of positive infants was significantly higher than of negative infants (P = 0.02). Positive infants tended to have severe bronchiolitis. Co-infection with C. trachomatis exhibited significantly more severe disease than in negative infants (P = 0.00). The mean severity score of positive infants was higher than negative (6.2 ± 3.1, 4.7 ± 2, respectively, P = 0.008).

Table 2.

Demographic and clinical data of C. trachomatis-positive and -negative infants.

	C. trachomatis-positive (n = 21)	C. trachomatis-negative (n = 71)	P value
Demographic data
Age (months) (mean ± SD)	2.9 ± 1.6	2.9 ± 1.7	0.804
Gender (n (%))
Male	9 (42.9)	38 (53.5)	0.390
Female	12 (57.1)	33 (46.5)
Clinical data
Fever (n (%))			0.061
Yes	–	12 (16.9)
No	21 (100)	59 (83)
Wheezing on admission (n (%))			0.01*
Yes	17 (81)	32 (45.1)
No	4 (19)	39 (54.9)
Crackles (n (%))			0.131
Yes	4 (19)	26 (36.6)
No	17 (81)	45 (63.4)
Respiratory rate (/min) (median ± IQR)	63.9 ± 11.5	57.1 ± 9.5	0.02^†
Severity score^‡ (median ± IQR)	6.2 ± 3.1	4.7 ± 2	0.008^†
Severity score (n (%))			0.00*
Mild	6 (28.6)	20 (28.2)
Moderate	8 (38.1)	50 (70.4)
Severe	7 (33.3)	1 (1.4)
Supplemental oxygen therapy (n (%))	11 (52.4)	17 (23.9)	0.017*
Duration of supplemental oxygen therapy (days (range))	1 (0–6)	0.7 (0–7)	0.006^†
Duration of cough before admission (days) (mean ± SD)	5.3 ± 4.1	6 ± 4.6	0.335
Laboratory findings
White blood cell (/mm³) (mean ± SD)	10.7 ± 4.3	11.3 ± 5.6	0.867
Eosinophile count (%) (mean ± SD)	1.3 ± 1.9	1.1 ± 1.6	0.718
C-reactive protein (mg/dL) (mean ± SD)	0.9 ± 0.9	1.9 ± 1.6	0.759

C. trachomatis, Chlamydia trachomatis; IQR, interquartile range; SD, standard deviation.

Chi-square test.

^†Mann–Whitney U test.

^‡Severity score: each clinical component (respiratory rate, clinical assessment of the infants breathing behaviour, wheezing and general situation) was scored in the range of 0–3. Scores were then added, which were divided into three groups: 0–3 points, 4–8 points and 9–12 points: mild, moderate and severe, respectively, defining the severity of bronchiolitis.⁹

Discussion

Our study suggests that C. trachomatis causes acute wheezing in infants and its presence implies a more severe disease status. Most of the C. trachomatis-positive infants were co-infected with respiratory viruses. Bacterial co-infections together with respiratory viral infections were reported in children of different age groups by several studies.^7,8,10–13

Recent studies have investigated the clinical characteristics of atypical bacterial pathogen associated with AB that have been considered to affect its clinical course.⁸ In clinical practice, it is known that wheezing is rarely observed in C. trachomatis pneumonia.¹² It is also known that pneumonic crackles may be heard on auscultation with wheezing.¹³ The main problem is that there is no specific test or clinical features to distinguish the causative agent of AB. C. trachomatis pneumonia is not easy to differentiate from other acute lower respiratory infections, particularly from AB caused by other agents. In our study, most C. trachomatis-positive infants presented with wheezing, and although C. trachomatis is an interstitial pneumonia, crackles were observed less in the C. trachomatis-positive infants. These findings suggest that the presence of wheezing without crackles does not distinguish between C. trachomatis pneumonia or acute viral bronchiolitis in infants aged <6 months. Our findings also do not support any statistically significant difference with eosinophile counts.

A major limitation factor in our study was the small number of patients. In addition, our study population was not evaluated for type of delivery, the presence of maternal cervicovaginal secretion or of co-existent conjunctivitis, type of cough and whether antibiotic treatment was given before admission.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Sarlangue

Castella

. Chlamydia infection in neonates and infants. Arch Pediatr 2005; 12: 32–36.

Tipple

Beem

Saxon

. Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than 6 months of age. Pediatrics 1979; 63: 192–199.

Darville

Chlamydia Infections. In: Remington

Klein

Wilson

et al. (eds). Infectious Diseases of the Fetu and Newborn Infant, 7th edn. Philadelphia, PA: Elsevier Saunders, 2010, pp. 600–600.

Berry

Gamieldien

Fielding

. Identification of new respiratory viruses in the new millennium. Viruses 2015; 7: 996–1019.

Miron

Srugo

Kra-Oz

et al.

Sole pathogen in acute bronchiolitis: is there a role for other organisms apart from respiratory syncytial virus?

Pediatr Infect Dis J 2010; 29: 7–10.

Korppi

Leinonen

Mäkelä

et al.

Mixed infection is common in children with respiratory adenovirus infection. Acta Paediatr Scand 1991; 80: 413–420.

Chen

Tang

et al.

Characteristics of Chlamydia trachomatis infection in hospitalized infants with lower respiratory tract infection. J Microbiol Immunol Infect 2007; 40: 255–264.

Pientong

Ekalaksananan

Teeratakulpisarn

et al.

Atypical bacterial pathogen infection in children with acute bronchiolitis in northeast Thailand. J Microbiol Immunol Infect 2011; 44: 95–100.

Wang

Milner

Navas

et al.

Observer agreement for respiratory signs and oximetry in infants hospitalized with lower respiratory infections. Am Rev Resp Dis 1992; 145: 106–115.

10.

Carballal

Mahony

Videla

et al.

Chlamydial antibodies in children with lower respiratory disease. Pediatr Infect Dis J 1992; 11: 68–71.

11.

Souza

Girão

Simões

et al.

Chlamydia trachomatis: a major agent of respiratory infections in infants from low-income families. J Pediatr (Rio J) 2012; 88: 423–429.

12.

American Academy of Pediatrics. Chlamydia trachomatis. In: Kimberlin DW, (ed.) Red Book: 2015 Report of the Committee on Infectious Diseases, 30th edn. Elk Grove Village, IL: American Academy of Pediatrics, 2015, p.288.

13.

Walsh-Kelly

Hennes

. Do clinical variables predict pathologic radiographs in the first episode of wheezing? Pediatr Emerg Care 2002; 18: 8–11.