Insights into pulmonary lophomoniasis infection in a Bruton's disease patient; A case report study and literature review

Abstract

Introduction

Lophomonas infection is a rare respiratory illness caused by parasites, mostly reported in immunocompromised patients. X-linked agammaglobulinemia (XLA), or Bruton's disease, is a primary immunodeficiency caused by a defective Bruton's tyrosine kinase (BTK) gene. This defect results in a deficiency or absence of functional BTK protein, leading to significantly reduced or absent B lymphocytes and serum immunoglobulin levels.

Case presentation

A 21-year-old male patient was admitted to our service exhibiting a six-week history of fever, dyspnea, and productive cough. The patient's condition deteriorated despite prior outpatient management. Following abnormal laboratory values and computed tomography, bronchoscopy was performed. Microscopic evaluation of the bronchoalveolar lavage fluid revealed the presence of viable, oval-shaped, flagellated Lophomonas protozoa.

Conclusion

In evaluating immunocompromised patients with sustained respiratory symptoms, clinicians should consider opportunistic infections, such as pulmonary lophomoniasis, in their differential diagnosis. Delayed intervention in this patient population may lead to irreversible adverse sequelae.

Introduction

Bruton's disease, a primary immunodeficiency disorder classified as X-linked agammaglobulinemia (XLA), results from mutations in the Bruton’s tyrosine kinase (BTK) gene [1]. This rare condition affects approximately 3–6 males per million and is linked to mutations located in the Xq21.3-Xq22 region [2]. The essential function of BTK in B cell development is highlighted by the nearly complete absence of B cells (< 2 %) and the lack of precursor B cell differentiation in the bone marrow of individuals with these pathogenic mutations. Consequently, lymphocytes in both blood and tissues cannot differentiate into plasma cells, leading to significantly reduced levels of all immunoglobulin classes and markedly impaired antibody responses. Consequently, patients with XLA are susceptible to a range of bacterial infections caused by various extracellular pathogens, as well as to viral and parasitic infections [3]. The occurrence of multiple recurrent respiratory infections, coupled with associated inflammation, contributes to the development of bronchiectasis. This condition perpetuates a detrimental cycle of inflammation and tissue damage, which further increases the risk of pulmonary infections [4].

Lophomonas spp. is an anaerobic, multiflagellate parasitic protozoan classified within the phylum Parabasalia. This organism inhabits the intestines of specific insects, predominantly cockroaches, as an integral component of their microbiome [5]. Humans can acquire infection by inhaling cysts present in the feces of these insects. Once inhaled, the cysts develop into multiflagellate trophozoites that adhere strongly to the respiratory mucosa, where they secrete proteases that induce a chronic inflammatory response reminiscent of asthma. Although the pathogenic mechanisms of Lophomonas spp. Given that the parasite remains inadequately characterized, it is proposed that it modifies the architecture and function of respiratory epithelial cells, thereby leading to inflammation. This inflammatory response may subsequently result in respiratory symptoms and tissue damage, thereby playing a critical role in the progression of the associated disease [6], [7].

The occurrence of pulmonary infections caused by Lophomonas has gained attention as an emerging health concern. This parasite can infect immunocompetent individuals as well, although its prevalence is notably higher among those with immune deficiencies. Clinical symptoms and radiographic findings associated with Lophomonas blattarum (L. blattarum) are often non-specific. Therefore, a microscopic examination of respiratory secretions is crucial for accurate diagnosis, as this organism can resemble other infections. Confirmation of this diagnosis can be achieved through bronchoscopy smears or bronchoalveolar lavage (BAL) samples [8].

New advancements in medical science have markedly improved treatment modalities and the overall quality of life for patients afflicted with immunodeficiency disorders. However, the increased vulnerability of these individuals to opportunistic infections underscores the critical need for timely diagnosis and intervention, requiring a high degree of clinical vigilance and specialized knowledge in the relevant medical field. Furthermore, the occurrence of lophomonas infection in Bruton's disease is exceedingly rare worldwide and, to our knowledge, remains unreported in the literature. This case study presents the diagnosis and management of a 21-year-old male patient with Bruton's disease and concomitant Lophomonas infection.

Case presentation

A 21-year-old male with a history of Bruton's disease (XLA) (with a mutation in the BTK gene), managed with monthly intravenous immunoglobulin (IVIG) therapy since the age of two, was referred to the Respiratory Medicine Department at Sayyad Shirazi Hospital in Gorgan, Iran. The patient reported a six-week history of fever, chills, and productive cough with whitish-yellow sputum, for which previous outpatient treatment had proven ineffective. He also described experiencing weakness, lethargy, and persistent fatigue but denied any hemoptysis.

Upon physical examination, the patient's vital signs were as follows: blood pressure 115/7 mmHg, pulse rate 76 bpm, respiratory rate 19 breaths per minute, body temperature 37.1 °C, and an oxygen saturation of 93 % on room air. Auscultation of the lungs revealed respiratory crackles. Cardiac auscultation was unremarkable, with normal S1 and S2 heart sounds. Abdominopelvic examination yielded normal results, with no evidence of splenomegaly, hepatomegaly, or lymphadenopathy.

Initial evaluation included laboratory investigations and a computed tomography (CT) scan of the lungs. Hematological analysis revealed anemia and leucocytosis. Inflammatory markers were elevated, with an erythrocyte sedimentation rate (ESR) of 52 mm/s and a C-reactive protein (CRP) concentration reported as negative. Immunoglobulin assays demonstrated normal IgM and IgG levels but decreased IgA and IgD (Table 1). A SARS-CoV-2 polymerase chain reaction (PCR) assay was performed, and the result was negative. CT imaging of the lungs revealed a tree-in-bud pattern and bronchiectasis, predominantly in the lower lobes (Fig. 1).

Table 1.

Laboratory test results for the studied patient.

Laboratory test	Findings	Normal Range	Laboratory test	Findings	Normal Range
WBC	13.8	4–10 × 103/µL	IgA	13	70–400 mg/ml
Hb	11.5	12–16 g/dL	IgG	881	700–1400 mg/ml
Plt	382	150–450 × 103/µL	IgD	58.2	> 132.1 mg/l
Urea	23	15–45 mg/dl	IgM	161	40–230 mg/ml
Creatinine	1	0.7–1 mg/dl	U/A	Normal	-
AST	24	< 40 U/L	ESR	52	< 10 mm/hr
ALT	13	< 40 U/L	CRP	3.4	< 6
Alk.p	245	143–362 U/L

WBC: white blood cell, Hb: hemoglobin, Plt: Platelet, AST: aspartate aminotransferase, ALT: alanine transaminase, Alk.p: alkaline phosphatase, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, Ig: immunoglobulin; U/A: urine analysis.

Fig. 1.

CT imaging of the lungs demonstrated a tree-in-bud pattern and bronchiectasis, with a primary distribution in the lower lobes.

Given the patient's medical history, abnormal CT findings, and persistent respiratory symptoms, a fiber optic bronchoscopy was performed. Three sputum samples were collected for culture, and BAL was performed to assess for Bacillus of Koch (BK), Lophomonas, and bacterial/fungal infections. Microscopic examination of the BAL fluid revealed the presence of numerous live, oval, flagellated Lophomonas protozoa (Fig. 2), while bacterial and fungal cultures were negative.

Fig. 2.

Microscopic analysis of the bronchoalveolar lavage (BAL) fluid indicated the presence of a significant number of viable, oval-shaped, flagellated Lophomonas protozoa.

Based on the positive BAL result, a diagnosis of Lophomonas infection was confirmed. The patient was treated with metronidazole (500 mg thrice daily for two weeks), resulting in clinical improvement. He was discharged in stable condition with oral medication prescriptions.

Discussion

X-linked agammaglobulinemia (Bruton's disease; XLA) is a rare primary immunodeficiency mostly seen in young males, characterized by a genetic anomaly in BTK that results in B lymphocyte deficiency, agammaglobulinemia, and heightened susceptibility to recurrent infections. Morbidity and mortality in XLA patients are most frequently attributed to infection and chronic lung disease, the latter often a sequela of repeated pulmonary infections [9], [10]. Recent studies examining XLA patient cohorts have documented the prevalence of infections and associated mortality. Pulmonary infections represent the predominant infectious manifestation and a significant contributor to mortality in this population. A 2022 study by O’Toole D et al. reported an 88 % incidence of respiratory infections among XLA patients, with chronic lung disease—frequently stemming from recurrent lower respiratory tract infections—emerging as a common and life-threatening complication affecting 53 % of patients [11]. Given these patients' heightened vulnerability to pulmonary infections, investigation into opportunistic etiologies is advisable, particularly in the presence of persistent pulmonary symptoms.

While sufficient IgG trough levels are typically considered protective against severe infections [12], Paccoud et al.'s research indicates that, despite a reduction in infection rates following immunoglobulin replacement therapy (IgRT), a significant proportion of patients (over 50 %) continued to experience at least one serious infection. Furthermore, a disproportionate number of lower respiratory tract infections (54.3 %) occurred within a smaller group (28.3 %) with confirmed bronchiectasis [13]. Similarly, despite receiving immunoglobulin replacement therapy (IgRT) and maintaining normal IgG levels, our patient continued to exhibit persistent respiratory symptoms refractory to inpatient treatment. The presence of bronchiectasis, confirmed via lung CT scan, along with further investigation, ultimately resulted in a diagnosis of pulmonary lophomoniasis.

L. blattarum, an anaerobic protozoan initially identified in the cockroach intestine in the 1860s, has been recognized since the 1990s as a potential opportunistic pathogen in the human lower respiratory tract. Transmission electron microscopy has elucidated the organism's defining ultrastructural features, including the parabasal body, the axial filament, and the absence of mitochondria [14]. It typically presents with atypical, non-specific clinical manifestations, primarily affecting the respiratory system, and is likely transmitted via airborne routes [15]. Studies in China, Peru, Iran, Mexico, and India have reported Lophomonas infection prevalence rates ranging from 8 % to 30 % among patients with respiratory symptoms [16]. Recent case studies from 2024 have documented instances of L. blattarum infection in patients with complex medical histories, such as brain tumors, diabetic mellitus, systemic lupus erythematosus, and anthracosis [5], [8], [15], [17]. Another case reported the concurrent presence of L. blattarum, tuberculosis, and a hydatid cyst in a pediatric patient with autism [18].

The morphological differentiation of L. blattarum from ciliated epithelial cells by light microscopy poses considerable diagnostic challenges, potentially leading to misidentification. Therefore, diagnostic procedures such as bronchoscopy biopsy smears, sputum smears, or BAL are valuable for accurately identifying L. blattarum in affected individuals [5], [8]. A 2022 review by Nakhaei M et al. of lophomoniasis cases from 1993 to March 2020 globally (307 cases) reported a mean patient age of 23.7 years, with a range of 1 month to 84 years. Bronchoalveolar lavage (BAL) was the predominant diagnostic method [19]. Another study in 2024 by Mewara et al. indicated that cough, fever, and expectoration were the most prevalent symptoms of lophomoniasis, affecting nearly 71 %, 60 %, and 46 % of patients, respectively. A substantial proportion of patients (89.6 %) presented with comorbidities. The diagnosis was primarily achieved through BAL samples (82.7 %), with microscopic examination demonstrating a 100 % detection rate, while PCR testing yielded a detection rate of approximately 35 % [20]. Similar to our case, our patient was a 21-year-old male patient who was immunocompromised and had a history of fever, chills, and productive cough. Diagnostic evaluation, specifically BAL sampling coupled with microscopic analysis, confirmed the presence of pulmonary lophomoniasis infection.

Considering the observed incidence of pulmonary lophomoniasis in Iran and the differential therapeutic medication required, clinicians should maintain a high index of suspicion for pulmonary lophomoniasis in immunocompromised patients presenting with persistent, progressive, or treatment-refractory respiratory symptoms.

This study is strengthened by the documentation of a rare Lophomonas infection in a patient with Bruton's disease (XLA) for the first time and the successful mitigation of complications through prompt diagnosis and targeted treatment. However, a key limitation was reliance on an external facility for a definitive Lophomonas diagnosis, resulting in procedural delays. Despite these diagnostic delays, the patient's condition was closely monitored, and symptoms were effectively managed.

Conclusion

Due to the patient's immunocompromised state and heightened susceptibility to opportunistic infections, vigilance and early clinical suspicion are crucial for identifying such infections, including pulmonary lophomoniasis, as clinical and paraclinical findings are often nonspecific. Prompt identification and appropriate therapeutic intervention are critical, as they may significantly enhance patient prognoses by mitigating disease progression and optimizing health outcomes.

Patient perspective

The patient was willing to present and share his rare infectious disease with doctors worldwide. Due to timely diagnosis, the patient was treated and recovered completely. All of the mentioned factors led to patient satisfaction with the process of diagnosis and treatment.

CRediT authorship contribution statement

Mohaddeseh Dankoub: Writing – review & editing, Methodology, Investigation. Mohammad Hadi Tajik Jalayeri: Writing – review & editing, Supervision, Project administration, Conceptualization. Mahdi Mazandarani: Writing – review & editing, Writing – original draft, Supervision, Methodology, Investigation. Narges Lashkarbolouk: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation.

Ethics approval

Written informed consent was obtained from the patient to publish this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. The purpose of this case report was completely explained to the patient, and he was assured that the researchers would keep her information confidential. This case report was performed in line with the Declaration of Helsinki principles. Ethical approval is not required for this study following local or national guidelines.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Funding

The authors declare that no funds, grants, or other supports were received during the preparation of this manuscript.

Competing Interests

The authors declare that they have no competing interests.

Availability of data and material

The datasets used during the current study are available from the corresponding author on reasonable request. All data generated or analysed during this study are included in this article. Further inquiries can be directed to the corresponding author.