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Severe community-acquired pneumonia caused by Chlamydia pecorum

Open AccessPublished:October 06, 2022DOI:https://doi.org/10.1016/j.ijid.2022.09.037

      HIGHLIGHTS

      • We report the first case of human Chlamydia pecorum pneumonia.
      • C. pecorum infection was identified by metagenomic next-generation sequencing and complement fixation test.
      • The patient was a farmer with diabetes and had close contact with sheep.
      • High fever, dry cough, and pulmonary consolidation are the main features.

      Abstract

      Chlamydia pecorum is a zoonotic pathogen. Here, we report the first case of human infection with C. pecorum. A man aged 51 years with high fever and dry cough was diagnosed with severe community-acquired pneumonia and respiratory failure. C. pecorum was found responsible for the infection, which was detected from bronchoalveolar lavage fluid through metagenomic next-generation sequencing. C. pecorum infection was further identified by quantitative polymerase chain reaction and complement fixation test. The patient's condition improved rapidly after targeted treatment. He was a farmer with diabetes mellitus and had a history of close contact with sheep, which might result in C. pecorum infection. Our report could provide a direction for the diagnosis and treatment of human C. pecorum pneumonia.

      Keywords

      Introduction

      Chlamydia is a genus of gram-negative, obligate intracellular pathogens, which currently comprise 13 species and three candidate species (
      • Bommana S
      • Polkinghorne A.
      Mini review: antimicrobial control of chlamydial infections in animals: current practices and issues.
      ). Most of them have significant impacts on the health of humans or animals. Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci are the major species that infect humans and can cause a variety of diseases (
      • Elwell C
      • Mirrashidi K
      • Engel J.
      Chlamydia cell biology and pathogenesis.
      ).
      Chlamydia pecorum infects a wide range of animal hosts, including sheep, goats, cattle, pigs (
      • Walker E
      • Lee EJ
      • Timms P
      • Polkinghorne A.
      Chlamydia pecorum infections in sheep and cattle: a common and under-recognised infectious disease with significant impact on animal health.
      ), and wildlife, such as koalas (
      • Polkinghorne A
      • Hanger J
      • Timms P.
      Recent advances in understanding the biology, epidemiology and control of chlamydial infections in koalas.
      ). Infection with C. pecorum can present a number of clinical manifestations, such as arthritis, endometritis, conjunctivitis, infertility, enteritis, vaginitis, pneumonia, and mastitis (
      • Jelocnik M
      • Frentiu FD
      • Timms P
      • Polkinghorne A.
      Multilocus sequence analysis provides insights into molecular epidemiology of Chlamydia pecorum infections in Australian sheep, cattle, and koalas.
      ;
      • Polkinghorne A
      • Hanger J
      • Timms P.
      Recent advances in understanding the biology, epidemiology and control of chlamydial infections in koalas.
      ;
      • Walker E
      • Lee EJ
      • Timms P
      • Polkinghorne A.
      Chlamydia pecorum infections in sheep and cattle: a common and under-recognised infectious disease with significant impact on animal health.
      ). These infections are an important source of economic loss for livestock producers (
      • Walker E
      • Jelocnik M
      • Bommana S
      • Timms P
      • Carver S
      • Polkinghorne A.
      Understanding the health and production impacts of endemic Chlamydia pecorum infections in lambs.
      ). Nevertheless, there are no case reports of human infection by C. pecorum.

      Case presentation

      A man aged 51 years was admitted to Qitai Hospital of the Sixth Division of Xinjiang Production and Construction Corps (Xinjiang, China). He complained of a 3-day history of high fever, with a temperature up to 39.5°C, and a 1-day history of dry cough. He denied shivers, nasal obstruction, pharyngalgia, dizziness, headache, or chest pain. At the beginning of the illness, he received some medicine orally or intravenously in a local hospital, but his symptoms persisted. The patient had a 4-year history of diabetes mellitus and took metformin and acarbose to control blood glucose levels. As a farmer, he raised more than 40 sheep.
      On admission, physical examination showed a temperature of 38.5°C, heart rate of 72/min, respiratory rate of 20/min, PaO2 of 58 mm Hg, SaO2 of 90%, and fine crackles in the right lung. A chest computed tomography scan showed consolidation in the right middle lobe and patchy infiltration in the left upper lobe (Figure 1a, c). Bronchoscopy revealed slight edema of the bronchial mucous membrane in the right lung. Laboratory investigations showed white blood cell of 4.90 × 109/l (normal 3.5-9.5 × 109/l), neutrophil of 3.35   ×  109/l (normal 1.8-6.3 × 109/l), lymphocyte of 1.18  ×  109/l (normal 1.1-3.2 × 109/l), C-reactive protein of 185.10 mg/l (normal 0.068-8.2 mg/l), procalcitonin of 1.266 ng/ml (normal <0.05 ng/ml), erythrocyte sedimentation rate of 85 mm/h (normal 0-15 mm/h), hemoglobin A1c of 10.06% (normal 3.60-6.00%), and fasting blood sugar of 11.73 mmol/l (normal 3.90-6.10 mmol/l).
      Figure 1
      Figure. 1Images of chest computed tomography. (a, c) On the day of admission. (b, d) 28 days after discharge.
      Serological tests for Mycoplasma pneumoniae immunoglobulin (Ig)M, C. pneumoniae IgM, Legionella pneumophila IgM, and Mycobacterium tuberculosis IgG proved negative. No abnormalities were found in the blood culture. Bronchoalveolar lavage was conducted; however, the antiacid staining and culture of bronchoalveolar lavage fluid (BALF) were negative. Considering the symptom of persistent high fever and the possibility of rare pathogens infection, the patient's BALF was sent for metagenomic next-generation sequencing (mNGS) (Genskey, Beijing) on the day of admission. A total of 906 unique DNA reads mapping of the C. pecorum genome were reported. Some oral microorganisms, such as Streptococcus infantis, Neisseria elongata, Fusobacterium periodonticum, and Veillonella dispar, were also detected in BALF, but all of their reads did not exceed 70. To confirm the results of mNGS, quantitative polymerase chain reaction (qPCR) amplifying 16S ribosomal RNA gene of C. pecorum was performed on the same sample and showed an average critical threshold value of 27 (F-5′-AGTCGAACGGAATAATGGCT-3′ and R-5′-CCAACAAGCTGATATCCCAC-3′) (
      • Walker E
      • Moore C
      • Shearer P
      • Jelocnik M
      • Bommana S
      • Timms P
      • et al.
      Clinical, diagnostic and pathologic features of presumptive cases of Chlamydia pecorum-associated arthritis in Australian sheep flocks.
      ). The PCR product was verified by sequencing. Serum samples were further analyzed for anti-Chlamydia antibodies using the complement fixation test. The antibody titer in the convalescent serum (1: 128, 28 days after discharge) increased remarkably versus the acute-phase serum (<1: 4, on admission), indicating a recent C. pecorum infection.
      On admission, the patient was diagnosed with severe community-acquired pneumonia and respiratory failure. Empiric treatment with intravenous moxifloxacin (0.4 g every day) was given for 4 days. Body temperature returned to normal within 2 days. On the third day of admission, mNGS analysis revealed the possibility of infection with C. pecorum. The patient was discharged the next day and switched to oral doxycycline (0.1 g every 12 hours) and moxifloxacin (0.4 g everyday) for 2 weeks. He had a return visit 28 days after discharge and denied clinical symptoms. Chest computed tomography showed the absorption of the inflammatory sites in the lungs (Figure 1b, d). In addition, C. pecorum was not detected again in BALF by mNGS.

      Discussion

      Chlamydia are common causative organisms of human community-acquired pneumonia. C. pecorum has been reported to induce animal pneumonia. A number of cases of cattle pneumonia caused by C. pecorum have been demonstrated in the UK (
      • Wheelhouse N
      • Longbottom D
      • Willoughby K.
      Chlamydia in cases of cattle pneumonia in Scotland.
      ). C. pecorum is also implicated in a few sporadic cases of respiratory disease in sheep (
      • Biberstein EL
      • Nisbet DI
      • Thompson DA.
      Experimental pneumonia in sheep.
      ). The patient in this case was a farmer and had a history of close contact with sheep, which might result in C. pecorum infection. Before the onset of his illness, two of his sheep showed signs of persistent mild conjunctivitis, which is common in C. pecorum-infected sheep, but others displayed no signs of ill health (
      • Walker E
      • Jelocnik M
      • Bommana S
      • Timms P
      • Carver S
      • Polkinghorne A.
      Understanding the health and production impacts of endemic Chlamydia pecorum infections in lambs.
      ). In addition, diabetes mellitus might also contribute to the patient's infection. History of livestock exposure, high fever, dry cough, and elevated inflammatory biomarkers, coupled with pulmonary consolidation, may guide early clinical diagnosis of C. pecorum pneumonia.
      Intracellular pathogens are usually difficult to culture and isolate. The general methods to diagnose C. pecorum infection are qPCR and complement fixation test. qPCR provides a rapid and definitive diagnosis of C. pecorum, which is currently the most widely used method (
      • Walker E
      • Moore C
      • Shearer P
      • Jelocnik M
      • Bommana S
      • Timms P
      • et al.
      Clinical, diagnostic and pathologic features of presumptive cases of Chlamydia pecorum-associated arthritis in Australian sheep flocks.
      ). mNGS, an emerging technique, represents an unbiased and rapid diagnostic tool that is useful for the diagnosis of unknown diseases (
      • Chiu CY
      • Miller SA.
      Clinical metagenomics.
      ). In the current case, the mNGS reported some unique reads mapping of the genome of C. pecorum but not other Chlamydia, implying that mNGS might be appropriate for the diagnosis of C. pecorum infection. Antibiotic treatment for chlamydial infection is important. In vitro susceptibility test of C. pecorum to antibiotics showed that macrolides, tetracyclines, and quinolones are all effective (
      • Pudjiatmoko Fukushi H
      • Ochiai Y
      • Yamaguchi T
      • Hirai K
      In vitro susceptibility of Chlamydia pecorum to macrolides, tetracyclines, quinolones and beta-lactam.
      ). In this case, the patient was treated correctly, and his condition improved rapidly.
      In summary, to the best of our knowledge, we report the first case of C. pecorum infection in humans. Human infection with C. pecorum might be underreported, underdiagnosed, or misdiagnosed. Microbiologists and clinicians should be aware of the zoonotic potential of C. pecorum. It is vital to identify what symptoms can present with C. pecorum infection. The mNGS method can help clinicians provide direction for the diagnosis of diseases, especially for rare or difficult cases.

      Author contributions

      LZC and LH collected clinical and laboratory data. SYW and LJX assisted with data analysis. SFZ integrated the data and wrote the manuscript. All authors read and approved the final manuscript.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Ethical approval

      Written informed consent for publication was obtained from the patient.

      Declaration of Competing Interest

      The authors have no competing interests to declare.

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