Introduction
Rickettsia felis (R. felis) is a globally recognized intracellular pathogen belonging to the spotted fever group of Rickettsia, infecting a wide range of mammals, humans, and ectoparasites, thus raising public health concerns worldwide.1 The process of diagnosing R. felis encephalitis is often fraught with complexities that lead to significant delays in patient care.2 Recent studies in China suggest that approximately 2.14% of patients presenting with fever of unknown origin (FUO) were found to be infected with R. felis (4/187 cases).3 The rise in detection of R. felis infections can largely be attributed to the increased utilization of metagenomic next-generation sequencing (mNGS), a powerful diagnostic technology that enhances pathogen identification.4,5 This advanced method transcends traditional diagnostic techniques that typically depend on preconceived notions of the pathogens involved, enabling the detection of numerous pathogens—such as bacteria, fungi, viruses, and parasites—directly from clinical specimens. With R. felis emerging as a notable infectious agent, its identification across the United States, Europe, Africa, and most recently in China points to its increasing relevance in contemporary medicine. Acknowledgment of R. felis infections is intensifying, particularly with the development of more sophisticated molecular diagnostic instruments. Remarkably, only two documented clinical infection cases attributed to R. felis have emerged in Guangdong, China to date.3 Typically presenting with vague symptoms like fever, rash, or gastrointestinal issues, respiratory manifestations of R. felis infections remain exceedingly rare and are scarcely reported. This case report chronicles a pulmonary infection stemming from Rickettsia felis in a male patient, whose recent Clonorchis sinensis infection and corticosteroid usage add layers of complexity to the clinical scenario, underlining the need for advanced diagnostic methods like mNGS to identify potential co-infections.
Case Presentation
In May 2023, a 43-year-old male patient was referred to our hospital, presenting with a persistent cough and fever (Timeline in Figure 1). Twelve days prior to his admission, the patient experienced a high-grade fever peaking at 39.1 °C, accompanied by an exacerbating cough. Initial screenings at a local hospital for Cytomegalovirus and other pathogens returned negative despite the patient undergoing empirical antiviral and antibacterial treatments (oseltamivir, moxifloxacin, and piperacillin-tazobactam), which did not ameliorate his hypoxemia, cough, and fever. Following an episode of wheezing and dyspnea, a chest computed tomography (CT) scan revealed bilateral pulmonary infiltrates. Physical examination upon arrival at our facility indicated that the patient had a respiratory rate of 35 breaths per minute and oxygen saturation at a manageable 96% while on high-flow nasal cannula (HFNC) treatment with a fraction of inspired oxygen (FiO2) of 0.60 and a flow rate of 50 liters per minute. Auscultation uncovered bilateral wet rales within the lungs, along with observable lower extremity edema, while the skin and oropharynx showed no signs of rashes or tick-bite wounds.
The patient, who resides in Shenzhen, China, reported daily consumption of one pack of Chinese liquor but had no history of cigarette smoking or ownership of pets. His potential exposure to stray cats increased suspicion of zoonotic transmission, even as he could not recall any tick or mite bites leading up to his illness. Previously healthy, he experienced fatigue and jaundice a month before admission, prompting a visit to a local facility that identified eggs of Clonorchis sinensis through stool microscopy. This resulted in a diagnosis of clonorchiasis, leading to a treatment regimen of prednisone and albendazole. Follow-up assessments confirmed the resolution of the Clonorchis sinensis infection.
Upon admission, laboratory tests indicated elevated levels of highly sensitive C-reactive protein (hs-CRP), procalcitonin, and conjugated bilirubin (detailed in Table 1). In light of these lab findings, the patient was initiated on a broad-spectrum antibiotic course of intravenous piperacillin-tazobactam and moxifloxacin. Unfortunately, by the second day of hospitalization, the patient’s shortness of breath intensified, necessitating endotracheal intubation, sedation, and mechanical ventilation. The patient’s APACHE II score was recorded at 18, indicating a critical illness scenario. On day three, peripheral blood and bronchoalveolar lavage fluid (BALF) samples underwent metagenomic next-generation sequencing (mNGS) using the MGISEQ-200 platform (China). Acute kidney injury (AKI) developed, subsequently requiring continuous renal replacement therapy (CRRT) via central venous catheter. On day four, mNGS results confirmed Rickettsia felis presence, exhibiting 4,764 high-confidence sequence reads, 346,796 bp of genome coverage, with an average depth of 1.21X. Of note, Rickettsia felis DNA contributed to 23.35% of the BALF genome coverage. Additional findings included Human betaherpesvirus 5 (CMV) with 8,567 reads, and Escherichia coli with 2,296 reads in the BALF. In blood samples, CMV was detected with 5,047 reads (Table 2). Notably, microscopy of the BALF did not reveal any parasites, and subsequent stool microscopy returned negative for Clonorchis sinensis eggs. Following these revelations, treatment involved oral doxycycline (100 mg twice daily), intravenous ganciclovir, and continuation of piperacillin-tazobactam, resulting in a marked clinical improvement. By the tenth day of hospitalization, the patient had been successfully weaned off mechanical ventilation and continued recovery. On the twelfth day, ganciclovir was ceased due to low-level cytomegalovirus viremia (Figure 2). He was ultimately discharged on the seventeenth day without the necessity for supplemental oxygen.
Discussion
The nonspecific nature of symptoms associated with R. felis infections increases the likelihood of misdiagnosis or underdiagnosis compared to other febrile diseases. The traditional quantitative PCR (qPCR) method, though preferred for suspected rickettsial disease, can be impeded by the clinical variability among patients presenting with ambiguous symptoms.24 In such cases, metagenomic next-generation sequencing (mNGS) offers a broader and more effective approach for pathogen screening and detection.
mNGS represents a groundbreaking and swift pathogen detection technique, capable of directly sequencing DNA or RNA extracted from clinical samples. Its applications span various medical disciplines, setting it apart from conventional diagnostic approaches by enabling simultaneous detection of a myriad of pathogens within a single sample, without reliance on a prior hypothesis from the clinician. This ability makes it especially potent for identifying rare and novel infectious agents, showcasing the unparalleled benefits of mNGS. Furthermore, results can be generated within 24 hours, significantly expediting pathogen identification. The accumulation of successful case reports and extensive research underscores mNGS’s transformative potential in enhancing diagnostic capabilities against infectious diseases.
Conclusion
In summary, swift identification of pathogens and immediate initiation of appropriate antibiotic therapy are paramount for achieving favorable outcomes in infectious disease management. Advanced molecular diagnostic tools like mNGS stand to expedite the accurate identification of infectious agents within clinical environments.
Abbreviations
R.felis, Rickettsia felis; mNGS, metagenomic next-generation sequencing; FUO, fever of unknown origin; CT, computed tomography; HFNC, high-flow nasal cannula; FiO2, fraction of inspired oxygen; APACHE Acute Physiology and Chronic Health Evaluation; BALF, blood and bronchoalveolar lavage fluid; AKI, acute kidney injury; CRRT, continuous renal replacement therapy; PCT, procalcitonin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; qPCR, quantitative polymerase chain reaction; tNGS, targeted next-generation sequencing.
Data Sharing Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Ethical Approval
This study was approved by the committee on the ethics of medicine, Shenzhen Second People’s Hospital (2022007).
Consent for Publication
Written informed consent was obtained from the patient for publication of this case report. The consent form is available for review by the editor upon request. Details concerning the case can be published without necessitating institutional approval.
Author Contributions
Funding
This research received support from the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (No. SZGSP006), the Sanming Project of Medicine in Shenzhen (No. SZSM202211016), and the Shenzhen Second People’s Hospital Clinical Research Fund in association with the Shenzhen High-level Hospital Construction Project (Grant Nos. 20223357008 and 2023xgyj3357003).
Disclosure
References
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Introduction: The Case of Rickettsia felis – The Flea with Flair
Alright, folks, gather ‘round! Today we’ve got a tale of a pathogen with more twists and turns than a soap opera plot line—Rickettsia felis. Now, this isn’t just your run-of-the-mill germ; it’s an intracellular pathogen that doesn’t just occupy space in mammals, humans, and those charming ectoparasites we all love to hate. Nope, it specializes in bringing spine-chilling encephalitis and fever of unknown origin into the party. Who doesn’t love a good mystery, right?
Let’s paint you a picture. In China, as it turns out, this little nuisance has been detected in about 2.14% of patients suffering from FUO. You see, the diagnostic process here is as straightforward as IKEA assembly instructions—lots of pieces, tons of confusion, and maybe an incomplete toolkit! Thanks to our shiny new friend, metagenomic next-generation sequencing (mNGS), we’re able to cut through the diagnostic fluff, catching the sneaky R. felis in the act. This technology is like the Swiss army knife of pathogen detection: it doesn’t just identify one or two suspects; it takes a bloody roll call of potential pathogens in your system. Fantastic, right?
Case Presentation: A Cough with a Side of Encephalitis
Now, let’s drop into May 2023, where we find our star, a 43-year-old male from Shenzhen. He’s already got more drama than a reality TV show contestant! Twelve days pre-admission, he’s rocking a fever peaking at a whopping 39.1 °C and the cough of a lifelong chain smoker. Yet, our brave patient doesn’t smoke! Oh the irony!
Things escalated fast. After initial treatments that targeted everything but the kitchen sink—like antiviral and antibacterial therapies—his cough and fever were still RSVPing to the party. They didn’t get the memo when our patient sought urgent care for breathing troubles. A chest CT then revealed bilateral pulmonary infiltrates because, apparently, nature’s way of saying: “You’ve got issues!”
Diagnosing the underlying conditions of this cough was no easy task. Our buddy lived a life as intoxicating as the one pack of Chinese liquor he downed daily while dodging tick bites and stray cats. And just to spice things up, he had the delightful task of dealing with a pre-existing Clonorchis sinensis infection. Let’s just say, if he was looking for sympathy, there was barely room for it in the hospital!
A Twisty Diagnostic Journey
Upon entering the hospital, the medical team realized they were dealing with a case that was more than just a chapter in a medical textbook. He’s presenting with elevated inflammatory markers, but despite several attempts at traditional diagnostics—like blood tests, CT scans, and even some rather aggressive antibiotics—a proper diagnosis was still playing hard to get.
It’s at this point where our techie friend, mNGS, enters the scene. With a mere blood and BALF sample, out pops the name Rickettsia felis alongside some viral and bacterial party crashers. It’s like someone opened a can of medical whoop-ass! mNGS identified 4,764 high-confidence sequence reads of the rickettsial DNA, proving it had set up camp in our patient’s lungs. The level of coverage would make any scientist weep with joy!
But wait, there’s more! Concurrently, our patient developed acute kidney injury and needed CRRT. Seriously, it was like a game of medical whack-a-mole! Fortunately, once treated with oral doxycycline and ganciclovir, he started to show improvement faster than a contestant on a cooking show who suddenly remembers the secret ingredient. By the 17th hospital day, he was discharged without the need for supplemental oxygen. Note to self: never underestimate a good dose of proper antibiotics combined with modern technology.
This is Why We Can’t Have Nice Things!
Now, let’s talk about the big bad wolf in this whole narrative—diagnosis. Because, let’s face it, the symptoms of R. felis would be easy to dismiss as just another case of the sniffles. Fever, rash, gastrointestinal woes… if I had a dollar for every time someone mistook chills for a night out, I could probably fund the next breakthrough in pathogen research!
mNGS, our superhero, saves the day by elucidating the wider web of infectious agents where R. felis is lurking. It bypasses the need for guessing games and delivers rapid results, essentially slapping those old-school diagnostics upside the head. With its ability to analyze vast amounts of data quickly, we’re finally getting ahead of the game. No more playing hide and seek with pathogens!
Conclusion: The Future Looks Bright (and Informative!)
In conclusion—what a journey! From the deep, murky depths of obscure fevers to the limelight of modern sequencing, this case shows just how crucial quick pathogen identification is for patient recovery. The marriage of classic clinical acumen with innovative technology like mNGS is paving the way for a more informed and effective healthcare approach. Keeping our eye on these pathogens can help save lives, enhance treatment efficacy, and perhaps, just maybe, stop our patients from getting too fancy with those pesky strays!
Remember, folks, keep your eyes peeled for those little critters that might be working harder than they should! And never underestimate advancements in technology—they’re here to help, often with a cheeky sense of humor!
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Discussion: The Broader Implications of Rickettsia felis
As we venture beyond this particular case, it’s essential to recognize the broader significance of Rickettsia felis in the world of infectious diseases. This pathogen, long considered a relatively obscure entity, is now demanding attention due to its increasing reported cases globally. A quick glance at the literature reveals its presence in places as diverse as Mexico, Taiwan, and Senegal, indicating a disturbing trend of emerging zoonotic infections (Zavala-Velazquez et al., 2006; Tsai et al., 2008; Socolovschi et al., 2010).
This case shines a light on the need for heightened awareness among healthcare providers regarding non-traditional infections like R. felis, especially in areas where patient histories may include exposure to fleas or ticks. Furthermore, the rising incidence of such diseases calls for improved surveillance and quicker response strategies. The use of next-generation sequencing technologies could vastly enhance pathogen detection capabilities, shortening the time it takes to reach a definitive diagnosis and radically improving patient outcomes.
Conclusion: A Call to Action
the tale of our patient offers a unique glimpse into the complexities of diagnosing and treating an infection caused by Rickettsia felis. It serves as both a cautionary tale and a beacon of hope, showcasing modern advancements in medical diagnostics and therapeutics. As we continue to battle emerging infectious threats, let’s ensure we stay one step ahead of these crafty pathogens. Remember, folks, knowledge is power, but in this case, a solid diagnostic toolkit is even more vital. Stay alert, stay informed, and never underestimate the fleas!
