Metagenomic next-generation sequencing is capable of generating large-scale sequence data sets that unbiasedly describe the genomic content of entire microbial communities (bacterial, viral, and eukaryotic organisms)(9). According to reported research, when mNGS identified a microbe (species level) whose relative abundance is more than 30% at the genus level in bacteria or fungi, it can potentially be regarded as a causative pathogen(10). In this mNGS report, both Aspergillus terreus and Chlamydia abortus met the Criteria.
Aspergillus terreus produces spores that disperse efficiently in the air and are prevalent in tropical and subtropical regions(11). Aspergillus terreus causes invasive aspergillosis (IA) in immunocompromised patients, especially those who suffer from neutropenia and are under high-dose steroid treatment(12). This previously healthy patient did not possess these risk factors, we considered it as contamination and did not start anti-fungal treatment. As human infection with Chlamydia abortus is very rare, the possibility of contamination should be excluded(13). After checking the lab record, the technician of Genskey denied Chlamydia abortus detected before this case, excluding the possibility of contamination in the laboratory environment. Nasal swab multiplex PCR for 13 respiratory pathogens indicating positive for genus Chlamydia as well consistent with the sequencing result. The positive metagenomic transcriptome sequencing result implies that the organism was “active”, as well supporting the diagnosis. As the patient was improving and recovered, we believe it is Chlamydia abortus causing this severe pneumonia and hypoxemia.
Chlamydiaceae is of the order Chlamydiales, which is a family of obligate intracellular Gram-negative bacteria. Underwent a number of taxonomic reclassifications, the genus Chlamydia (which is under the family Chlamydiaceae)currently includes 14 species((Chlamydia abortus, Chlamydia avium, Chlamydia buttons, Chlamydia caviae, Chlamydia felis, Chlamydia gallinacean, Chlamydia muridarum, Chlamydia pecorum, Chlamydia pneumonia, Chlamydia poikilothermic, Chlamydia psittaci, Chlamydia serpents, Chlamydia suis and Chlamydia trachomatis)) and four Candidatus species(14).
Before 1990, Chlamydia psittaci encompassed a huge group of strains been grouped by a number of methods. Andersen grouped strains of Chlamydia psittaci into serotype I by Serovar-Specific Monoclonal Antibodies, which latterly been grouped as Chlamydia abortus (15).
Besides being associated with enzootic abortion in small ruminants, Chlamydia abortus causes pig abortion in both intensive and extensive production systems(16.17). In this case, it seems possible that pigs from the farm are transmitters of this zoonotic agent to the farmer. There is published research involving experimental infections with Chlamydia abortus that has identified the ability of this pathogen to cause pulmonary disease in animal species(18.19). In Ortega et al case, the veterinary researcher developed pan-lobar pneumonia ten days after operating the suspension of Chlamydia abortus sprayed on animals, through serological and molecular analysis the microorganism was confirmed. Interestingly, two asymptomatic colleagues of the patient showed antibody production against Chlamydia abortus(8). In another case, the patient did not directly contact the animals but just handled contaminated clothing of her husband and developed Chlamydia abortus infection and abortion(7). From these cases, we can see that Chlamydia abortus can be highly transmissible, and conditionally may cause fatal conditions as it is in our case.
Admittedly, there are some pitfalls in this case. According to the mNGS result, the possibility of co-infection with Aspergillus terreus should not have been ruled out arbitrarily, and anti-fungal treatment may be reasonable. Considering the rarity of human Chlamydia abortus infection, an alternative method should be obtained to confirm the pathogen diagnosis. A seroepidemiological study of the animals on that farm could have revealed more information. Unfortunately, it was more than a month later when we realized the issues above, the patient is recovered and discharged, and the family had already sold all the animals on the farm to meat factories when they were informed the patient’s severe disease was caused by a zoonotic pathogen.
From this case, we can see that Chlamydia abortus infection in human may as well cause severe pneumonia with hypoxemia and need ECMO support. Thus, veterinarians and public health officials should be aware of possible severe pulmonary infection due to Chlamydia abortus.