Bordetella bronchiseptica Infection in an Immunocompetent Adult and a Literature Review on this Rare Zoonosis

Steven Kompogiorgas; Marousa Kouvela; Georgios Giannikos; Konstantinos Kotsifas; Stavroula Boulia; Georgios Poupouzas; Evangelos Balis

doi:10.37871/jbres2059

ISSN: 2766-2276

Biology Group 2025 January 31;6(1):086-097. doi: 10.37871/jbres2059.

Subject area(s)

Infectious Diseases
Virology

| | |

Case Report

Bordetella bronchiseptica Infection in an Immunocompetent Adult and a Literature Review on this Rare Zoonosis

Steven Kompogiorgas^1*, Marousa Kouvela², Georgios Giannikos¹, Konstantinos Kotsifas¹, Stavroula Boulia¹, Georgios Poupouzas¹ and Evangelos Balis¹

¹First Pulmonary Department, Evangelismos, General Hospital of Athens, Greece ²Oncology Unit, Third Department of Internal Medicine, Sotiria General Hospital for Chest Diseases, National and Kapodistrian University of Athens, Greece

*Corresponding authors: Steven Kompogiorgas, First Pulmonary Department, Evangelismos, General Hospital of Athens, Greece E-mail:

Received: 15 January 2025 | Accepted: 31 January 2025 | Published: 31 January 2025

How to cite this article: Sagne SN, Sene O, Dieng I, Diallo MK, Ndoye AM, Mhamadi M, Sankhe S, Sall Y, Diop B, Faye O, Sow A, Diallo B, Diagne MM, Loucoubar C, Fall G, Barry MA. Bordetella bronchiseptica Infection in an Immunocompetent Adult and a Literature Review on this Rare Zoonosis. J Biomed Res Environ Sci. 2025 Jan 31; 6(1): 082-085. doi: 10.37871/jbres2059, Article ID: jbres1757

Keywords

Imported
Severe
Crimean-Congo hemorrhagic fever
Comorbidities
Senegal 2023

Find and get this Article from other databases

Export Citation CrossMark Publons Harvard Library HOLLIS GrowKudos Search IT Google Scholar Academic Microsoft Scilit Semantic Scholar Universite de Paris UW Libraries SJSU King Library NUS Library McGill DET KGL BIBLiOTEK JCU Discovery Universidad De Lima WorldCat DTU VU on WorldCat ResearchGate

Abstract

Introduction: Bordetella bronchiseptica, a Gram-negative coccobacillus, studied for its role in Canine Infectious Respiratory Disease and porcine atrophic rhinitis. It is an opportunistic pathogen with few reported cases of immunocompetent infection.

Aims: We will describe the demographic, clinical, radiological, diagnostic and therapeutic characteristics of a rare zoonosis in the literature, and outcomes.

Case: A 59 year old patient had presented due to non-resolution of her chronic productive cough.

Bronchoscopy revealed Bordetella bronchiseptica, her history of animal exposure was elucidated.

Conclusion: The majority of patients with this infection are HIV+ with low CD4 counts. Consolidations are the most common finding on imaging. Usually diagnosed by sputum culture and commonly treated by β-lactams. Our case shares significant overlap with the commonly found characteristics from the literature, and recovered. It is always important to consider zoonoses in the history-taking of immunocompromised and, even in immunocompetent patients.

Case Report

A 59 year old woman presented in February 2024 to the Outpatient Department due to non-resolution of her productive cough of 3 months. She had initially received a 7 day course of oral Clarithromycin, and mentioned some degree of symptomatic improvement. Her cough, however, persisted. She self-medicated with an inhaler containing fluticasone/vilanterol. This offered no further relief.

One month prior to her attendance in our hospital’s outpatient department, she sought a second medical opinion. The result of this examination was a prescription for oral co-amoxiclav. On the third day of her regimen, she noticed an erythematous exanthem. Her prescribing doctor stopped the co-amoxiclav, and started her on a 7 day course of moxifloxacin in addition to singulair and rupatadine. A cardiological consult was sought, and no pathological findings were reported.

She presented to us several days after the end of this treatment with a subjectively improved yet persistent productive cough. She characterized the timing of it as a single episode coughing bout that produced a large volume of purulent sputum, with little to no symptoms for the rest of the day.

Our patient did not mention chest pain, dyspnoea, fever or symptoms from the upper airways. She provided us with laboratory results from a private lab, consisting of a sputum culture showing normal flora and a negative Interferon Gamma Release Assay (IGRA) result.

On examination, she presented well with no evidence of distress. She was afebrile, with an SpO2 of 97% on room air. On auscultation, she had a diffuse expiratory wheeze with scattered ronchi. Her examination was otherwise unremarkable.

The past medical history of our patient includes a radical hysterectomy 22 years ago that was complicated by disseminated intravascular coagulation, ileus secondary to abdominal adhesions that was operated 16 years ago and osteoporosis. She is an ex-smoker of approximately 30 years who quit successfully 3 years ago. Additionally she mentioned a tendency to self-medicate with inhalers of fluticasone-vilanterol when she feels unwell. Her smoking habit was irregular as she smoked socially and it was too irregular to quantify a pack-year value. She mentioned no known allergies.

A thoracic CT scan was ordered, which did not show any specific findings to explain her symptomatology. It only mentioned non-specific findings such as air-trapping in the expiratory phase in the upper lobes and right middle lobe, and small bi-basal linear atelectasis of no clinical significance.

In order to find an aetiological link to her chronic non-resolving cough, her auscultation findings and the lack of imaging findings for guidance, she was referred for bronchoscopy at Evangelismos General Hospital of Athens.

During the bronchoscopy, the inspection of the airways gave us clues to an underlying infective aetiology due to diffuse oedematous changes in the submucosa, mucus plugs and an area of anthracosis at a sub-segmental entrance of the posterior segment of the left lower lobe. Specimens were taken in the form of a bronchoalveolar lavage (BAL, neutrophilia of 44% on flow cytometry) and bronchial washings that were sent for flow cytometry and microscopy/culture/sensitivity testing. No other findings were reported.

The cultures reported the presence of Bordetella bronchiseptica > 15,000 CFU/ml, and the sensitivity testing gave Intermediate Sensitivity to each antibiotic tested, we report each tested MIC; Cefotaxime: 16 (IE), Gentamicin: 4 (IE), Ciprofloxacin: 0.5 (IE), Levofloxacin: 0.5 (IE), Moxifloxacin: 1.0 (IE), Tigecycline: < 0.5 (IE), Meropenem: 4 (IE), Piperacillin/Tazobactam; < 4 (IE), Ceftazidime: 2 (IE), Amikacin: 16 (IE), Colisin < 0.5 (IE).

Based on the above testing, she was started on a regimen of Levofoxacin 750 mg twice daily, per os, for ten days. As the regimen progressed, she did not report symptomatic improvement but by the end of treatment her sputum culture was negative for B. bronchiseptica, and gradually her symptoms resolved on subsequent follow-up.

It is important to underscore the following. When the culture results confirmed the presence of B. bronchiseptica, our patient volunteered the fact that not only did she have a pet dog, but 1 month prior to the start of all her symptoms, she adopted a stray dog that was ill with respiratory symptoms. The veterinarian prescribed several antibiotic courses and a course of steroids, and her dog still had difficulty in resolving the infection. By the time of the final follow-up, her dog had not completely recovered.

Literature Review

Introduction

The etiological agent under review, Bordetella bronchiseptica has been a known cause of respiratory veterinary disease for over a century. Initially a subject of interest to veterinarians for both the medical, and economic implications of communicable disease, especially in the pre-antibiotic era. With the advent of improved diagnostics, the first human hosts were documented, and a renewed interest in this pathogen would ferment.

Initially it was isolated under the name Bacillus bronchicannis coined by Ferry himself in 1910 (and one of a significant series of name changes and re-classifications). This landmark paper is no longer available to us, published in the then American Veterinary Review (now known as JAVMA) titled “A preliminary report of the bacterial findings in canine distemper” [1]. In actual fact, this paper erroneously attributed2 canine distemper to what would eventually be named B. bronchiseptica, only to be discovered later that this upper respiratory tract infection is caused by a paramyxovirus.

B. bronchiseptica is a small, Gram-negative, flagellated coccobacillus that measures 0.2-0.5 µm by 0.5-2.0 µm. Like other species of its genus, it is classified under the phylum of Proteobacteria, the class of Betaproteobacteria, the order of Burkholderiales and the family of Alcaligenaceae. The approved species within this genus is found in the List of prokaryotic names with standing in nomenclature (as regulated by the International Committee on Systematics of Prokaryotes). This zoonosis in particular has been studied extensively for its role in canine infectious tracheobronchitis (kennel cough, now known as Canine Infectious Respiratory Disease) or porcine atrophic rhinitis [3]. They currently stand at sixteen species.

It is a bacterium capable of forming biofilms and toxins, but not the pertussis toxin produced only by B. pertussis. It is a motile organism with a flagellum, whose role extends beyond motility as demonstrated by mutant strains in flagellar proteins that were unable to form mature biofilms under laboratory conditions [4]. The pathogenicity of B. bronchiseptica is still similar to that of B. pertussis that is more familiar to pulmonologists and pediatricians especially as the cause of whooping cough in children.

The BvgAs locus is a highly conserved region (between B. bronchiseptica, B. pertussis and B. parapertussis) encoding for virulence factors which despite obvert similarities, result in a pleomorphic infectious picture across a wide range of mammal species. They encode for agglutinins (FHA) and fimbreae (Fim2, Fim3) to assist in establishing infection, the Adenylate Cyclase Toxin which is implicated in inhibiting opsonization/killing as well as inducing macrophage apoptosis and the Dermonecrotic toxin implicated in the severity of porcine atrophic rhinitis severity. Additional genes include Lipopolysaccharides (LPS and O Antigen) that modulate innate immunity and specific secretion systems (T3SS and BteA) whose needle-like structure is a delivery system for bacterial protein products into the cytosol of its targets [5,6]. Additionally a Type 6 Secretion System, as found in various Gram-negative bacteria, is a transport system that has a role virulence factor as seen in Franciella tularensis and Vibrio cholera in its anti-eukaryotic cell functions. It is currently implicated and being studied as a virulence factor in the intracellular survival strategy of B. bronchieseptica [7]. Additionally, B. bronchiseptica has been demonstrated in its isolation from human hosts at different points in time for strains to undergo what appears to be a form of antigenic variation In vivo [8].

Characteristically a pathogen of canines manifesting Canine Infectious Respiratory Disease (CIRD) syndrome, it is since proven to be a far more significant pathogen in canines than originally thought [2]. CIRD has been observed to be caused by B. bronchiseptica as the primary pathogen, or secondary to Canine Adenovirus Type 2 (CAV-2), Canine Parainfluenza Virus (CPiV), Canine Herpesvirus (CHV) and Canine Respiratory Coronavirus (CRCoV). The tracheobronchitis in canines manifests with coughing and nasal discharge [9]. In porcine hosts, it is the cause of bronchopneumonia and atrophic rhinitis. The latter is complicated by co-infection by Pasteurella multocida and Pseudomonas aeruginosa amongst others [10]. B. bronchiseptica has been isolated from other hosts including cats, rabbits, horses, turkeys, seals, guinea pigs, koalas, sea otters [11], mountain voles[12], rats & mice [13], polar bears[14], baboons[15], sheep [16], sloths [17], and monkeys [18].

The first reported case of B. bronchiseptica in human beings dates back to the paper published by Brown in 1926 titled “Bacillus bronchiseptica infection in a child with symptoms of pertussis” in what was then, the Johns Hopkins Hospital Bulletin [1]. The paper is no longer available and the journal ceased publication in 1982.

B. bronchiseptica is very rarely encountered, in comparison to B. pertussis, a bacterium that causes pertussis (whooping cough) in children with over 150,000 new cases per year. Pertussis is communicable via droplet transmission mainly via coughing/sneezing. It is a cause of significant morbidity and mortality in infant populations. Pertussis classically appears as a mild fever and upper respiratory involvement with nasal discharge and a cough after a 7-10 day incubation. The cough characteristically contains a “whooping” inspiratory component, hence its namesake [19]. The clinical characteristics of B. bronchiseptica differ in essence as it is an opportunistic pathogen with only a very few reported cases of immunocompetent infection in the entirety of the literature.

In the process of conducting a literature review of published human cases of this very rare zoonosis, the decision was taken to adopt a search strategy without any limitation by the introduction of search terms and boolean operators due to the very few publications that exist on this topic. The PubMed search of “Bordetella bronchiseptica” resulted in an output of results just shy of 1700. In order to approach the literature review, papers were accessed that would provide information into the microbiology, molecular biology, veterinary medicine, host types, and finally, all reported human cases.

From the papers downloaded, 87 were included in the references as they were case reports with one or more unique patient. In total, a spreadsheet with 147 unique patients was created containing information (Table 1).

Table 1: Patient data.
Basic Demographics		Immunocompromised/Higher Risk Patient Categories Based On Co-Morbitities	Clinical Data
Sex (M/F)		Chronic Liver Disease [36-39] 4% of adults	Duration of presenting symptoms between immunocompetent/immunocompromised
Immunocompentent 27 adults, 10 children 48%/52%	Immunocompromised 93 adults, 17 children 59%/41%	Duration < 7d prior to presentation Adults 45.5%/40% Children 87.5%/60%	Duration > 7d prior to presentation Adults 54.5%/60% Children 12.5%/40%
Age Group Stratification between immunocompetent and immunocompromised		Chronic Kidney Disease/ESRD/dialysis [40-42] 6% of adults had CKD 8% of adults had ESRD or on dialysis	Presenting symptoms between immunocompetent/immunocompromised
Children 0-1 50%/6% 2-5 10%/18% 6-10 0%/24% 11-17 40%/54%	Adults 18-30 15%/18% 31-40 11%/16% 41-50 4%/15% 51-65 11%/28% > 65 59%/23%		Adults Dry Cough 15%/15% Productie Cough 54%/26% Chest Pain 8%/12% Dyspnoea 39%/29% Fever 62%/46%	Children Dry Cough 0%/21% Productie Cough 12.5%/64% Chest Pain 12.5%/21% Dyspnoea 25%/21% Fever 25%/21%
Immunocompetent Adult [21-35]		HIV-AIDS (including columns if ART was discontinued against medical advice/not on ART, CD4) [35,43-62] 35% of adults, of whom 60% discontinued their ART and 73% had a CD4 < 250 cells/μL	Animal exposure history Adults/Children Immunocompetent 82%/100% YES Immunocompromised 66%/94% YES
Immunocompetent Pediatric [34,94-101]		Malignancy [63-69] 27% of adults, 6% of children	Presence of respiratory failure Adults/Children Immunocompetent 40%/37.5% YES Immunocompromised 33%/31% YES
Table 1: Patient data.
Basic Demographics		Immunocompromised/Higher Risk Patient Categories Based On Co-Morbitities	Clinical Data
Sex (M/F)		Chronic Liver Disease [36-39] 4% of adults	Duration of presenting symptoms between immunocompetent/immunocompromised
Immunocompentent 27 adults, 10 children 48%/52%	Immunocompromised 93 adults, 17 children 59%/41%		Duration < 7d prior to presentation Adults 45.5%/40% Children 87.5%/60%	Duration > 7d prior to presentation Adults 54.5%/60% Children 12.5%/40%
Age Group Stratification between immunocompetent and immunocompromised		Chronic Kidney Disease/ESRD/dialysis [40-42] 6% of adults had CKD 8% of adults had ESRD or on dialysis	Presenting symptoms between immunocompetent/immunocompromised
Children 0-1 50%/6% 2-5 10%/18% 6-10 0%/24% 11-17 40%/54%	Adults 18-30 15%/18% 31-40 11%/16% 41-50 4%/15% 51-65 11%/28% > 65 59%/23%		Adults Dry Cough 15%/15% Productie Cough 54%/26% Chest Pain 8%/12% Dyspnoea 39%/29% Fever 62%/46%	Children Dry Cough 0%/21% Productie Cough 12.5%/64% Chest Pain 12.5%/21% Dyspnoea 25%/21% Fever 25%/21%
Immunocompetent Adult [21-35]		HIV-AIDS (including columns if ART was discontinued against medical advice/not on ART, CD4) [35,43-62] 35% of adults, of whom 60% discontinued their ART and 73% had a CD4 < 250 cells/μL	Animal exposure history Adults/Children Immunocompetent 82%/100% YES Immunocompromised 66%/94% YES
Immunocompetent Pediatric [34,94-101]		Malignancy [63-69] 27% of adults, 6% of children	Presence of respiratory failure Adults/Children Immunocompetent 40%/37.5% YES Immunocompromised 33%/31% YES
		Structural Lung Disease [70-72] 24% of adults, one immunocompetent adult, 82% of children	Imaging findings Immunocompetent/Immunocompromised
			Adults Consolidation 69%/44% Necrotic Features 15%/23% Effusion 8%/8% Normal CXR 8%/10%	Children Consolidation 50%/35% Normal CXR 0%/6%
		Transplant patients [73-79] 14% of adults, 18% of children	Complications Immunocompetent/Immunocompromised
			Adults Sepsis 4%/54% Intubation 19%/10% Opportunistic Infection 0%/14% Delay/Non resolution 4%/13%	Children Sepsis 0%/12% Intubation 20%/24% Opportunistic Infection 20%/53% Delay/Non resolution 20%/1%
		Auto-Immune disease under Treatment [33,34,35,80-87] 5% of adults	ICU Admission Adults 40% of immunocompetent and 19% of immunocompromised Children 37.5% of immunocompetent and 31% of immunocompromised
		Congenital defects of the immune system [33,34,35,80-87] 2% of adults, 16% of children	Diagnostic method leading to diagnosis/identification for B. bronchiseptica table2.
		Other Conditions [33,34,35,80-87] 12% of children	Admission duration between immunocompetent/immunocompromised Adults Mean inpatient days 14%/20% Mean ICU days 22%/17% Children Mean inpatient days 15%/28% Mean ICU days 0%/0%
		Immunocompromised Pediatric [35,88-95]	Treatment table 3.
			Outcome table 4.

In our review of the literature, 120 of 147 collected patients were adults and 25% of all patients were considered immunocompetent. The main category of immunocompromised or higher risk patients were due to HIV, of which 73% had CD4 counts lower than 250cells/μL and 21% had discontinued their antiretroviral therapy against medical advice. Other individual groups include malignancy, structural lung disease (mainly Cystic Fibrosis) organ transplants.

Results

Both immunocompetent and immunocompromised/higher risk adults had roughly equal distribution between acute and sub-acute/chronic presentations, with a distribution favoring longer symptom duration prior to presentation. Fever was present in 62% of immunocompetent adults as opposed to 42% of immunocompromised adults. Productive cough was encountered in 54% and 26% respectively. Children tended to present acutely (87% in immunocompetent and 60% in immunocompromised children), and only the immunocompromised/higher risk group favored productive cough (64%), largely due to the presence of children with cystic fibrosis in this category. Animal exposure was a significant presence in the history of infected individuals. There was a case of transmission between patients [85] within a paediatric hematology transplant ward. Immunocompetent patients also had less respiratory failure, shorter inpatient stay and less complications including septic shock, delayed or non-resolving pneumonia or secondary opportunistic/hospital acquired pathogen isolation.

The main imaging finding in patients was consolidation, and it was seen the most in immunocompetent individuals. Immunocompetent individuals had less necrotic features, and an equal chance of developing a pleural effusion.

The investigations leading to identification of the pathogen in adults or immunocompromised/higher risk children was by sputum culture (Table 2).

Table 2: Diagnostic method for B. Bronchiseptica only.
	Immunocompetent	Immunocompromised or At Higher Risk
Adults	n = 27	n = 10
Bal	19%	31%
Sputum Culture	48%	43%
Tracheal Aspiration	11%	10%
Blood Culture	7%	6%
Washing/Brushing	7%	2%
Fna/Biopsy	4%	5%
Nasal Swab	0%	3%
Others	22%	5%
	Maxillary sinus swab culture, cervical smear culture, ear swab culture, nasopharyngeal lavate culture	CSF culture, peritoneal dialysis culture, sinus swab culture, stool culture
Children	n = 93	n = 17
Bal	10%	17%
Sputum Culture	20%	82%
Tracheal Aspiration	30%	0%
Blood Culture	10%	6%
Washing/Brushing	0%	0%
Fna/Biopsy	0%	0%
Nasal Swab	0%	0%
Others	30%	6%
	Nasopharyngeal lavate culture, CSF culture	Throat swab culture
BAL: Bronchoalveolar Lavage; CSF: Cerebrospinal Fluid; FNA: Fine Needle Aspirate.

The population of immunocompetent children arrived to their diagnosis more commonly by tracheal aspirates, with sputum cultures coming a close second. More immunocompromised/higher risk patients underwent bronchoscopy and underwent BAL.

In terms of therapeutics, β-lactam based antibiotics and quinolone were the mainstay of adult prescriptions followed by macrolides and tetracyclines (Table 3).

Table 3: Treatment.
	Immunocompetent	Immunocompromised or At Higher Risk
Adults	n = 27	n = 10
Β-LACTAMS	56%	53%
Quinolones	26%	37%
Carbapenems	7%	15%
Linezolid	4%	2%
Clindamycin	7%	12%
Macrolides	11%	11%
Tetracycline	15%	18%
Amynoglycosides	11%	18%
Glycopeptides	7%	6%
Trimethoprim-Sulfamethoxazole	7%	17%
Anti Tb Group 1 Medications	4%	5%
Anti-Fungals	4%	3%
Anti-Virals	0%	2%
Children	n=93	n=17
Β-LACTAMS	33%	53%
Quinolones	7%	41%
Carbapenems	0%	0%
Linezolid	0%	35%
Clindamycin	4%	6%
Macrolides	11%	21%
Tetracycline	11%	6%
Amynoglycosides	7%	35%
Glycopeptides	0%	18%
Trimethoprim-Sulfamethoxazole	11%	24%
Anti Tb Group 1 Medications	4%	6%
Anti-Fungals	4%	12%
Anti-Virals	7%	0%

Immunocompetent children largely received β-lactams, followed by macrolides, tetracyclines and trimethoprim-sulfamethoxazole. Immunocompromised/higher risk children mainly received β-lactams, followed by quinolone, linezolid and aminoglycosides reflecting a more serious, hospital-based course of treatment.

Outcomes are displayed in table 4. All immunocompetent children recovered fully, and the immunocompromised/higher risk pediatric group had a 13% fatality rate. The adult groups both had a 72% full recovery rate, with a slightly higher fatality rate of 24% in immunocompetent adults compared to 20%.

Table 4: Outcome of B. Bronchiseptica infection.
	Immunocompetent	Immunocompromised or At Higher Risk
Adults
Recovery	72%	72%
Death	24%	20%
Recurrence	4%	1.5%
Persistent infection	0%	5%
Lost to follow up	0%	1.5%
Children
Recovery	100%	87%
Death	0%	13%
Recurrence	0%	0%
Persistent infection	0%	0%
Lost to follow up	0%	0%

Discussion

The discrepancy seen in the higher mortality rate observed in immunocompetent individuals is not easily explained. This is an unexpected finding from the data. One possible explanation can be attributed to a confounding effect due to the fact that four of the six adult immunocompetent deaths occurred in individuals in the > 65yrs age group, while the remaining two occurred in the 50-65 group. Thus, co-morbidity can be a possible cause. Additionally, it cannot be directly inferred from the literature if there were any delays in presentation that could have resulted in a more advanced infection at presentation, thus affecting prognosis. Difficulties in patient management were also not inferred. It is also worth noting that immunocompetent adults did not have any cases of persistent infection, although they did demonstrate slighter recurrence of infection.

Like the large majority of our collected cases, our case report follows the pattern of an individual who mentioned a history of infected animal exposure, developed symptoms and presented with a chronic productive cough. Her imaging was normal, unlike the majority of patients that presented with consolidations. In our case, the diagnostic identification occurred via bronchial washings instead of sputum cultures, and her treatment differed in the antibiotics used as she was initially treated with co-amoxiclav, but had to switch to levofloxacin based on sensitivity results. Her outcome of full recovery is consistent with the overall findings.

Conclusion

While it is good clinical practice when taking a history to fully document all environmental factors a patient has, it is essential to do so when assessing populations that are immunocompromised or otherwise vulnerable. The fact that a rare zoonosis has been seen in approximately 25% of the studied population who are fully immunocompetent, shows that this is not only a significant possibility, but the true prevalence of Bordetella bronchiseptica may even be underreported due to successful empirical treatment with β-lactams as a simple community-acquired lower respiratory tract infection whose aetiological agent is never isolated, perhaps making this a far more common infection that we think.