Two wrongs don’t make a right. Fifty wrongs, however, can make a scientific consensus. All it takes is a large enough number of researchers drawing similar conclusions from a big enough pile of bad data. A confirmation cycle sets in, and tentative suggestions begin to solidify into confident assertions. A weird idea that might be true becomes the thing that everybody knows.
Eventually, if the system is working properly, some spoilsport may return to the evidence and go through it all, item by item. If it turns out that the data and methods don’t support previous conclusions, the consensus melts away.
I’ll discuss a recent example of this, below. But first, I need to revisit an article I wrote nine years ago, after a friend sent me a video from Mexico, showing the contents of a bronchial lavage from a person who had nearly drowned in a river. The footage showed active ciliated cells from the poor victim’s lungs, which the medical investigators took to be some sort of ciliated protozoan.
As soon as I saw them, I recognized these “ciliates.” I’d seen the very same thing in my own saliva, almost twenty five years earlier!
A little research explained both cases: these were not protozoans at all, but ordinary ciliated epithelial cells–normal tissues from human lungs and nasal passages. It’s something that happens, occasionally: a few ciliated cells are torn loose, and keep on moving until their energy reserves run out.
As far as I was concerned, that little mystery was solved.
But while learning about this phenomenon, I ran into something rather creepy: medical case reports of a rare respiratory infection in human patients caused by an organism identified as Lophomonas blattarum.
This was NOT a creature that should be living in anybody’s lungs! Lophomonas blattarum is a parabasalid flagellate, an anaerobic protozoan normally found in the hindguts of cockroaches. Yet there was a growing body of literature describing it an opportunistic human parasite.
I was intrigued, and wrote a longish blog post about it: Is this a Parasite, or it Just Me?
At the time, I was skeptical of these case reports, because the microscopy in them was uniformly awful, and the authors made little attempt to reconcile their murky images with the known cellular features of Lophomonas blattarum. The morphological grounds for identifying these “organisms” as Lophomonas struck me as weak, however strong the clinical evidence might be.
Still, without a gene sequence from the supposed pathogen, it seemed like the question could not be put to rest.
Among the comments on my post were some helpful observations by Gillian Gile, who–unlike any of the clinicians who had diagnosed Lophomoniasis in their patients–had actually worked with the organism. At that time, she wrote: “I’ve seen Lophomonas blattarum from cockroaches, and the bundle of flagella moves quite differently from the waving cilia in that youtube video from Mexico. The real L. blattarum can actually swim from point A to point B. With no molecular evidence the jury is still out, but it doesn’t seem likely that Lophomonas is infecting human lungs.” (My emphasis)
Fakhar et al., 2019
It would be a few more years before the first molecular evidence did appear. The results, when they came, were a big surprise to me. In 2019, a group of parasitologists in Iran announced an apparent confirmation, by molecular methods, that Lophomonas was indeed present in a patient with bronchopulmonary disease. They published a paper with a justifiably self-congratulatory title: “First Molecular Diagnosis of Lophomoniasis: the End of a Controversial Story.”
The investigators took a sample from the nasal discharge of a 40 year old woman who was suffering from “rhinorrhea, sneezing, coughing, itchy throat and headache for a month.” They looked at a stained specimen of the discharge under a microscope and found it “positive for Lophomonas.”
They included a single image of the supposed organism, and it is as unconvincing as any I’ve seen before–a low-resolution micrograph showing a cell with a broad thatch of cilia distributed evenly across the anterior, rather than a narrowly concentrated apical “horsetail” of flagella, as is typical of Lophomonas.
The authors designed what they called “genus-specific” PCR primers, to selectively amplify a certain chunk of DNA (the SSU rRNA gene, widely used for phylogenetic work). If Lophomonas was present, these primers ought to amplify only the DNA from a certain gene in that particular organism.
They extracted DNA from their patient’s nasal discharge, along with a second sample from a healthy subject as a control, and then performed PCR on both.
Gel electrophoresis confirmed that genetic material from Lophomonas was present in the sick woman’s discharge, and not in the healthy control.
So, it seemed to be true: a gene from a cockroach symbiont really had been found in this poor woman’s lungs! She was treated with an antiprotozoal medication called metronidazole, and she got better. This did look like “the end of a controversial story”, as the paper’s title put it.
Subsequent clinical studies built on this work. New case reports appeared, and in many of them it was now stated as an established fact that Lophomonas blattarum could infect people. Numerous videos confidently labelled “Lophomonas spp.” were posted to YouTube. In 2022, another Iranian study was conducted, and the results were particularly startling. The authors examined 132 frozen bronchial lavage samples from patients hospitalized with a variety of respiratory conditions. Using similar methods to those described in Fakhar et al. (2019), they found that more than 1/4 of these patients (27.3%) tested positive for Lophomonas! A condition previously understood to be rare, was now described as “a common and emerging disease in the study area, southwestern Iran.”
Nguyen et al., 2023
Meanwhile, however, another group of researchers–including Gillian Gile, quoted above–undertook the investigation of the organism itself: True molecular phylogenetic position of the cockroach gut commensal Lophomonas blattarum.
The authors of that study dissected some actual cockroaches, and succeeded in establishing cultures of Lophomonas blattarum. They produced good photographic images of them, finally, and the images corresponded very well with illustrations in previous studies (like the one from Beams et al., posted above), showing a very narrow tuft of flagella at the apex of the cell, and a nucleus in the anterior of the cell. The organism in their images did not look much like the photos and videos of the supposed “Lophomonas” found in human “infections”.
The authors sequenced these cockroach commensals, and established their phylogenetic position, branching close to a genus of parabasalid termite symbionts called Trichonympha. They also looked more closely at the earlier sequences of putative “L. blattarum” taken from human samples, and found they were not closely related to Lophomonas blattarum at all, but were actually 99% similar with certain members of a different group of organisms called Trichomonadida (two genera in particular, Tetratrichomonas and Pentatrichomonas, one of which is known to live inside human bodies, and looks nothing like either Lophomonas or a ciliated epithelial cell).
As it turned out, none of the sequences taken from sick people in previous studies actually belonged to Lophomonas: “These data…indicate that no true L. blattarum sequences have yet been published from human lung samples.” (Nguyen et al., 2023)
Mewara et al., 2024
That study was followed, earlier this year, by a full review of all the existing literature on “lophomoniasis”: Lophomonas as a respiratory pathogen—jumping the gun.
The results are pretty devastating for this “emerging human pathogen”.
The authors analyzed all the photographic and video evidence in the published literature, applying the known morphological criteria for identifying Lophomonas. They found that none of the existing images of Lophomonas from human samples showed the characteristic features of the organism, such as a “tight anterior bundle of flagella, an anterior nucleus, the calyx surrounding the nucleus, or a posteriorly protruding axostyle.”
As it turns out, the differences between true Lophomonas and human epithelial cells are not subtle at all. Consider the following figure. The first three panels (A-C) show Lophomonas blattarum, and the second three (D-F) show human epithelial cells. Note the shape of the flagellar bundle in the anterior, the location of the nuclei (labelled “n”), and the overall appearance of the cell.
The video evidence is even more clear. The supplementary materials to the article include footage of genuine Lophomonas blattarum which can be downloaded and viewed. In that video, taken by Gillian Gile, a Lophomonas cell is seen moving purposefully forward, with the help of a narrowly concentrated tuft of flagella at the apex of the cell. Distinctive features of the cell, such as the axostyle and the calyx (both recorded by R. R. Kudo in the 1920s!), can be seen at certain points.
The efficient, directed movement of the cell has little resemblance to the feeble, rocking motion we often see in video of “Lophomonas” taken from human samples. Here is a typical example of that:
In another video from a recent paper, we see a cell with a broadly distributed “carpet” of cilia, going around in circles. This one is more vigorous, but its movements are just as aimless and ineffectual:
In their review of the literature, Mewara et al., 2024 also address the molecular evidence, reaffirming what had been shown in Nguyen et al.,2023: that the PCR assay used to amplify Lophomonas from BALF was not genus-specific at all, and readily amplified other organisms (in particular, certain trichomonads already known to live in human lungs and GI tracts).
Finally, the authors reviewed all the existing clinical evidence for “lophomoniasis,” and the medical case for the ailment seems to have fared just as badly. They found little consistency in the presentation of the “disease”, the ages or backgrounds of those affected, or the actual site of the infection. Evidence needed to single out L. blattarum as the causative agent was missing from the work that had been done.
Their meta-analysis uses methods and standards I don’t really understand, and I’m not competent to redescribe their results. Luckily, I don’t have to, because two of the authors have discussed their work in a conversation with two editors from the Journal of Clinical Microbiology. The video of that conversation has been posted to YouTube. If you’ve never considered the possibility that your lungs could be colonized by creatures from a roach’s rump, you probably don’t need to watch the video. However, if, like me, you’ve already been “infected” by this horrible idea, you might find it comforting:
References: Click here
