Lophomonas as a respiratory pathogen-jumping the gun

Abstract

Human infections with the protozoan Lophomonas have been increasingly reported in the medical literature over the past three decades. Initial reports were based on microscopic identification of the purported pathogen in respiratory specimens. Later, a polymerase chain reaction (PCR) was developed to detect Lophomonas blattarum, following which there has been a significant increase in reports. In this minireview, we thoroughly examine the published reports of Lophomonas infection to evaluate its potential role as a human pathogen. We examined the published images and videos of purported Lophomonas, compared its morphology and motility characteristics with host bronchial ciliated epithelial cells and true L. blattarum derived from cockroaches, analyzed the published PCR that is being used for its diagnosis, and reviewed the clinical data of patients reported in the English and Chinese literature. From our analysis, we conclude that the images and videos from human specimens do not represent true Lophomonas and are predominantly misidentified ciliated epithelial cells. Additionally, we note that there is insufficient clinical evidence to attribute the cases to Lophomonas infection, as the clinical manifestations are non-specific, possibly caused by other infections and comorbidities, and there is no associated tissue pathology attributable to Lophomonas. Finally, our analysis reveals that the published PCR is not specific to Lophomonas and can amplify DNA from commensal trichomonads. Based on this thorough review, we emphasize the need for rigorous scientific scrutiny before a microorganism is acknowledged as a novel human pathogen and discuss the potential harms of misdiagnoses for patient care and scientific literature.

Keywords: Lophomonas; cilia; ciliocytophthoria; flagellate; misidentification; parasites.

Fig 1

Light microscopic comparison of Lophomonas blattarum to human ciliated epithelial cells. (A–C) L. blattarum cells, unstained wet mounts, differential interference contrast microscopy. Note the concentrated tuft of long flagella subtended by the anteriorly located nucleus. A slight posterior protuberance formed by the distal tip of the axostyle is visible in (B). (A) Cell from a temporary culture with rice starch added to the medium. (B) Cell from a temporary culture with yeast added to the medium. Several ingested yeast cells are visible in the cytoplasm. (C) Cell isolated directly from a Blatta orientalis gut. (D–F). Human ciliated epithelial cells in respiratory specimens, unstained saline wet mounts, phase contrast microscopy. Note the distributed tuft of equal length, short cilia, covering the apical surface of the cell. A large, posteriorly located nucleus is visible in (D) and (E). (G–J) Fixed, stained mounts of intact, and degenerated ciliated epithelial cells. (G) Diff-Quik stained, air-dried preparation of normal ciliated respiratory epithelial cells mechanically exfoliated by bronchial brushing. Cell nuclei measure approximately 12–14 µm in diameter. (H) Papanicolaou-stained sputum specimen preserved in CytoLyt medium demonstrating numerous detached ciliated respiratory epithelial cells in various states of degeneration. Note that the terminal bar is readily apparent in many of the cells, allowing them to be readily recognizable as ciliated human cells. (I) Papanicolaou-stained bronchial brushing specimen preserved in CytoLyt medium demonstrating mechanically detached, normal, ciliated respiratory epithelial cells. Note the columnar shape with narrowed basilar region where the cell was previously attached to the basement membrane. (J) Papanicolaou-stained endocervical specimen preserved in CytoLyt medium demonstrating abundant detached ciliary tufts (ciliocytophthoria), in which only the cilia and terminal bar are apparent. Abbreviations: flagella (fl), nucleus (N), yeast cell (Y), protuberance due to axostyle (ax), cilia (C), terminal bar (tb), ciliocytophthoria (cy). All scale bars = 20 µm.

Fig 2

Reports of Lophomonas on Medline, Embase, and CNKI databases (till 16 May 2023).

Fig 3

PRISMA flowchart for inclusion of studies on Lophomonas.

Fig 4

Forest plot for the pooled prevalence of putative Lophomonas in patients either by microscopy or PCR.