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Clinical features and prognostic predictors of C. Psittaci Pneumonia: a systematic review and individual patient meta-analysis

BMC Pulmonary Medicine volume 25, Article number: 55 (2025) Cite this article

Abstract

Background

The clinical presentations and prognostic indicators of C. psittaci pneumonia are inadequately investigated currently. The objective of the study was to assess the clinical presentation of C. psittaci pneumonia and the risk factors for severe pneumonia, within a systematic review and individual patient meta-analysis.

Methods

We searched PubMed, CNKI, and Wanfang databases for case reports/series of proven/probable psittacosis published between 1st January 2000 and 28th February 2023, including all hospitalized individuals aged ≥ 18 years. Patient demographics, manifestations, diagnostic methods, and outcomes were summarized descriptively. Patients were divided into severe or non-severe pneumonia groups mainly according to the ATS/IDSA 2007 criteria. Prognostic predictors for severe C. psittaci pneumonia were identified using multivariate logistic regression.

Results

3062 articles of 196 (566 individual patient cases) were included in the final analysis. Patients with chronic cardiovascular disease face a significantly elevated risk of developing severe C. psittaci pneumonia (adjusted odds ratio (aOR) 2.63; 95% confidence interval (CI) 1.05–6.59; P = 0.039). Symptoms including dyspnea (aOR 4.88; 95% CI 3.19–7.46; P < 0.001), neuropsychiatric symptoms (aOR 3.58; 95% CI 2.05–6.28; P < 0.001), gastrointestinal symptoms (aOR 1.76; 95% CI 1.10–2.80; P = 0.018), or the presence of multilobar infiltrates on imaging (aOR 3.27; 95% CI 2.11–5.06; P < 0.001) upon admission frequently serve as indicators of severe pneumonia.

Conclusions

Chronic cardiovascular disease increases susceptibility to severe C. psittaci pneumonia. The presence of dyspnea, neuropsychiatric symptoms, gastrointestinal symptoms, and multilobar infiltrates upon admission merits clinicians’ attention, advocating for timely sample submission for metagenomic next-generation sequencing (mNGS) to ascertain the etiology.

Peer Review reports

Background

Psittacosis is a global systemic zoonosis caused by the obligate intracellular bacterium Chlamydia psittaci, with numerous laboratory-confirmed cases being reported in a growing number of countries [1,2,3,4], inducing substantial economic losses and creating a public health concern [5]. In 2012, a global meta-analysis on community-acquired pneumonia (CAP) revealed that Chlamydia psittaci constituted 1.03% of CAP cases [6]. A multicenter study in China recently highlighted the emerging significance of Chlamydia psittaci as a causative agent for severe community-acquired pneumonia (SCAP), accounting for 7.3% of total cases [7]. Mortality generally ranges from 5 to 40% in untreated patients, and it could be higher with co-infection [8]. The diagnosis of psittacosis poses a challenge. Most human Chlamydia psittaci infections remain undetected [9, 10] and the global misdiagnosis rate is as high as 50–80% [11, 12]. Therefore, the incidence and disease burden might be greatly underestimated [13].

The previous literature mainly included individual cases, lacking a summary of large samples [14]. Limited data and clinical misdiagnosis hindered a comprehensive understanding of the clinical characteristics of C. psittaci pneumonia [6, 12, 15, 16]. The widespread adoption of modern molecular detection technologies such as PCR and mNGS in clinical infectious disease diagnostics has led to an exponential increase in clinical reports [10, 17, 18]. Further research is warranted to deepen our understanding of C. psittaci pneumonia, including distinctions between severe and non-severe cases, as well as early prediction of severe cases to enable timely clinical interventions.

Hence, we conducted a systematic review of C. psittaci pneumonia to explore the clinical manifestations and prognostic factors of this atypical pneumonia.

Methods

Search strategies and information sources

We conducted an individual patient data (IPD) meta-analysis. First, only studies that met the inclusion criteria of containing individual patient data were considered. Then, from the eligible studies, we further selected individual patients who met the required criteria for inclusion in the analysis. This review was conducted according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [19] for transparent and comprehensive reporting. The study protocol was prospectively registered on the PROSPERO database (CRD42021247247). No documented review protocol exists for this meta-analysis. A systematic search employing predefined search strategies was conducted across PubMed, CNKI, and Wanfang databases. The following key terms, and multiple synonyms hereof, were used to build the search strategy: ‘psittacosis’ OR ‘Chlamydia psittaci’ OR ‘Chlamydophila psittaci’ OR ‘C. psittaci’ (Supplementary material, Appendix S1). The search scope was confined to human studies published in either English or Chinese from 1st January 2000 to 28th February 2023. Additionally, reference lists of pertinent articles were scrutinized for further inclusion.

Study selection

Search strategies were devised and executed by QQ. Jia, and initial findings were imported and consolidated into reference management software, ENDNOTE® (version X7). Following duplicate removal, titles, and abstracts of the remaining records were evaluated for eligibility. Subsequently, full texts of pertinent articles were retrieved and independently evaluated by two pairs of authors (ST. Liu & JB. Sun and J. Xu & X. Li). Disagreements over study inclusion were resolved by consensus. The list of published case reports/ series included in the review is shown in Supplementary material, Appendix S5.

Eligibility criteria

Published case reports/series of proven/probable C. psittaci pneumonia, as mainly defined by the Diagnosis and Treatment of Adults with Community-acquired Pneumonia guidelines published by the American Society of Infections and the American Thoracic Society(ATS/IDSA 2007 criteria) [20] and Psittacosis/Ornithosis (Chlamydophila psittaci) 2010 Case Definition published by CDC [21] in patients ≥ 18 years old were reviewed. Additionally, C. psittaci infection diagnosed through the mNGS test will also be included (Supplementary material, Appendix S2). For inclusion, the published cases must have had documentation of (i) demographics and history of contact with live poultry, (ii) comorbidities, (iii) method(s) of diagnosis, (iv) treatment process and strategy, and (v) patient outcomes. Conference abstracts, editorials, poorly described cases, review articles, or case series without primary data or where the analysis was pooled without the description of individual patient data were excluded. In addition to the severe pneumonia screening criteria outlined in ATS/IDSA 2007 guidelines, patients meeting any of the following criteria were categorized into the severe group: admission to the intensive care unit (ICU), necessitating cardiovascular support (vasopressors, inotropes, with or without extracorporeal membrane oxygenation (ECMO)), and death.

Data collection process and data items

Using standardized data extraction forms (Supplementary materials), data were extracted independently by the two author groups (as above) and compared. Discrepancies were discussed with X. Tong and DG. Wang as adjudicators. Initial data were collected after admission. Data extracted included the authors, the country of origin of the published cases, year of publication, patient demographics, underlying conditions/comorbidities, method of diagnosis, severity, clinical manifestations, imaging, and clinical outcomes.

Summary measures and statistical analysis

Data analysis was performed utilizing STATA 16.0 software (Stata Corp, College Station, TX, USA). Patient characteristics, manifestations, and methods of diagnosis were descriptively summarized. Categorical variables underwent assessment via the chi-squared test or Fischer’s exact test, while continuous variables were analyzed using the Wilcoxon-Mann-Whitney test. Predictive factors for severe patients were discerned through multivariate logistic regression. P < 0.05 was statistically significant.

Results

Patient demographics and methods of diagnosis

PRISMA diagram describes the articles and the case selection process (Fig. 1). 3062 articles of 196 (566 individual patient cases) were included in the final analysis. Among the 566 patients, the median (Interquartile Range, IQR) age was 60(49–69) years, with 341 (60.2%) being male. The severe group exhibited a higher proportion of males compared to the non-severe group (189/292, 64.7% versus 152/274, 55.5%; P = 0.025). A majority reported a history of contact with poultry (428/566, 75.6%) (Table 1). Most severe cases (217/292, 74.4%) met the IDSA/ATS 2007 criteria (Supplementary material, Appendix S3). Regarding diagnostic methods, the predominant approach involved mNGS analysis (495/566, 87.5%) of sputum, bronchoalveolar lavage fluid, or blood samples. Other diagnostic techniques included PCR (29/566, 5.1%), serology (25/566, 4.4%), and a combination of the aforementioned methods or alternative diagnostic modalities (clinical diagnosis or culture) (Supplementary material, Appendix S4).

Fig. 1
figure 1

PRISMA diagram describing the case selection process

Full size image

Patient comorbidities

Hypertension emerged as the most prevalent underlying condition (105/566, 18.5%), followed by diabetes (63/566, 11.1%), chronic cardiovascular disease (41/566, 7.2%), and other diseases. We observed that immunocompromised individuals, including those with diabetes, constituted only 14.3% (81/566) of the total population, with no significant difference between the two groups (49/292, 16.8% versus 32/274, 11.7%; P = 0.083). Among patients with severe C. psittaci pneumonia, the prevalence of comorbidities was greater (155/292, 53.1% versus 98/274, 35.8%; P < 0.001). Specifically, the severe group exhibited a greater prevalence of diabetes (44/292, 15.1% versus 21/274, 7.7%; P = 0.006) and chronic cardiovascular disease (32/292, 10.9% versus 9/274, 3.3%; P < 0.001) (Table 1).

Table 1 Clinical Data of patients with severe or non-severe psittacosis pneumonia
Full size table

Clinical manifestations

The most prevalent manifestations among patients included fever (545/566, 96.3%), followed by cough (418/566, 73.8%), dyspnea (245/566, 43.1%), fatigue (246/566, 43.5%), and chills (202/566, 35.7%). A subset of patients exhibited neuropsychiatric symptoms (114/566, 20.1%) and gastrointestinal symptoms (158/566, 27.6%), while a minority also experienced relative bradycardia, hemoptysis, rash, and limb swelling. Significant disparities were observed in the incidence of dyspnea (188/292, 64.4% versus 57/274, 20.8%; P < 0.001), neuropsychiatric symptoms (88/292, 30.1% versus 26/274, 9.5%; P < 0.001), and gastrointestinal symptoms (97/292, 33.2% versus 61/274, 22.3%; P = 0.004) between severe and non-severe patients, suggesting a heightened likelihood of these symptoms in the severe group (Table 1).

Prognostic predictors

The predictor variables (male, age, diabetes, hypertension, chronic respiratory disease, cardiovascular disease, chronic liver disease, fever, dyspnea, psychoneurotic symptom, gastrointestinal symptom, multiple lung lobes, pleural effusion, hepatic injury, hyponatremia) were selected based on clinical relevance. Chronic cardiovascular disease was associated with an increased risk of severe pneumonia (aOR 2.63; 95% CI 1.05–6.59; P = 0.039). Moreover, severe pneumonia patients were at greater risk of experiencing dyspnea (aOR 4.88; 95% CI 3.19–7.46; P < 0.001), neuropsychiatric symptoms (aOR 3.58; 95% CI 2.05–6.28; P < 0.001), gastrointestinal symptoms (aOR 1.76; 95% CI 1.10–2.80; P = 0.018), and multilobar infiltrates (aOR 3.27; 95% CI 2.11–5.06; P < 0.001) (Fig. 2).

Fig. 2
figure 2

Multivariate logistic regression analysis of the factors associated with progression to severe pneumonia. Abbreviations: CI, confidence interval

Full size image

Non-pharmacological treatments and overall mortality

A total of 32.3% (183/566) of the patients underwent invasive ventilation treatment, 4.9% (28/566) received continuous renal replacement therapy, and 5.3% (30/566) underwent ECMO. Mortality occurred in 4.6% (26/566) of patients, with a median (IQR) age of 64(51–69) and 65% (17/26) being male. While some deceased patients had underlying comorbidities, the proportion of immunosuppressed individuals was relatively low (2/26). Most deaths resulted from respiratory failure and septic shock [22, 23], although a few were attributed to myocarditis, pulmonary embolism, gastrointestinal bleeding, and multiple organ dysfunction syndrome [24, 25]. Moreover, the mortality rate may increase in cases of co-infection [26].

Discussion

This study provides a comprehensive systematic review of C. psittaci pneumonia, offering valuable insights and recommendations for its prevention, clinical diagnosis, and management.

The prognosis of psittacosis depends on the clinical severity, comorbidities, and the duration of treatment [6]. As appropriate antibiotic therapy is given, the cure rate of psittacosis is reported to be as high as 94.23% [23]. In our study, the mortality rate of hospitalized patients with C. psittaci pneumonia was 4.6%, which can reach up to 6.5% in severe cases. we observed that chronic cardiovascular disease was a significant risk factor for C. psittaci pneumonia. This may be related to the direct and autoimmune damage to the myocardium [27], as biopsy reveals the presence of inclusion bodies in myocardial cells [28,29,30]. Notably, five pregnant women included in the study experienced maternal or fetal death. Psittacosis during pregnancy is rare but can cause substantial maternal and fetal morbidity and mortality [4, 31]. Thus, pregnant women, patients with chronic cardiovascular disease, and people who are possibly infected with psittacosis should avoid contact with birds and livestock.

Chlamydia psittaci can infect patients of any age and sex. The incidence rate often reaches its peak in individuals aged 60 years. The proportion of males was 60.2%, and the proportion of males was greater in the severe group, which may be related to higher exposure potential [32]. Additionally, the proportion of patients with underlying diseases in the study was approximately 37.5%, and the prevalence of immunosuppressed conditions, including diabetes, was less than 15%. Hence, Chlamydia psittaci is generally not considered an opportunistic pathogen, and fortification of measures to mitigate exposure to live poultry is essential, even for individuals without immune deficiencies.

Additionally, 24.4% of patients had no direct contact with live poultry, which is consistent with the previous reports [14, 33]. We also found that a history of live poultry contact history was unrelated to the severity of the disease, which proves that a history of direct exposure to birds, while clinically enticing, is not particularly specific. Aside from direct contact with live poultry and excretion, spillover infections through human-to-human and even horse-to-human transmission pose an additional emerging public health threat [34, 35]. Therefore, primary care physicians and public health authorities must consider alternative transmission routes for this zoonotic agent in patients with suspected pneumonia of unknown origin.

In the acute phase of infection, leukocytes are usually normal or slightly reduced, but accompanied by a left shift [36]. In our study, 22.8% of patients had elevated leukocyte counts, while 59.9% had elevated neutrophil counts. Elevated leukocytes in the later stages of infection usually indicate the activation of systemic inflammation or co-infection with bacteria [37, 38]. Since neutrophils in patients with psittacosis are usually normal, CRP, interleukin-6 (IL-6), and procalcitonin have been recommended for monitoring therapeutic efficacy [36]. In terms of imaging, failure to receive timely treatment may lead to the fusion of multiple lesions and eventual dissemination throughout all lobes [14]. We found that the percentage of patients with pleural effusion was approximately 45%, which is consistent with previous research results [16]. In addition, severe patients have a greater probability of developing multilobar involvement and pleural effusion. Hence, the assessment of disease progression in patients can also be inferred from their imaging features at admission.

The in-hospital mortality rate was 4.6%, which increased to 8.9% in severe cases. Chlamydia psittaci primarily induces respiratory symptoms but can disseminate to multiple systems through the bloodstream [39,40,41], giving rise to diverse clinical manifestations and complications. We found that the presence of dyspnea, gastrointestinal symptoms, and neuropsychiatric symptoms on admission often indicates a poor prognosis. Additionally, other rare complications including rhabdomyolysis, meningitis, hemophagocytic syndrome, and even fulminant psittacosis are noteworthy [42,43,44,45,46,47]. According to the data from the CDC, the mortality rate of psittacosis is < 1% if diagnosed earlier and properly treated [48]. Thus, more frequent testing of CAP patients is recommended to reduce the diagnostic deficit and under-ascertainment.

In recent years, mNGS has emerged as a valuable tool for addressing the limitations of traditional detection methods [49,50,51,52], including culture, serology, and PCR techniques. One major finding is that due to the widespread application of mNGS, the diagnosis of atypical pathogens such as Chlamydia psittaci has increased [8]. In this study, 87.4% of patients were diagnosed through mNGS of sputum, bronchoalveolar lavage fluid, or blood samples, suggesting the potential greater contribution of Chlamydia psittaci to the etiology of CAP.

This study presents the largest cohort of psittacosis pneumonia cases to date, which reveals the clinical characteristics and predictive factors associated with severe psittacosis pneumonia, providing valuable insights for clinical practice. Unfortunately, our study has several limitations. First, there was insufficient information for the season- and area-specific estimates. The risk of exposure to C. psittaci is likely to differ among geographical areas and seasons. Second, due to the secondary data analysis, we lacked the opportunity to conduct a comprehensive analysis of the impact of pharmaceuticals on patient prognosis. In addition, the current inclusion criteria are almost exclusively for hospitalized patients, which does not apply to patients with C. psittaci pneumonia in primary care. However, further high-quality clinical studies are still needed to answer these questions.

Conclusion

In conclusion, psittacosis is a significantly underestimated disease, both in terms of its incidence and mortality rates. High-risk populations, including individuals with chronic cardiovascular disease and pregnant women, should avoid contact with birds and livestock. The CAP patients who present with dyspnea, neuropsychiatric symptoms, gastrointestinal symptoms, and multilobar infiltrates upon admission merit clinicians’ attention. We advocate timely sample submission for screening of Chlamydia psittaci. In patients with severe pneumonia, timely detection of mNGS in samples is recommended for prompt antibiotic treatment.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

Not applicable.

Funding

This work was supported by 1.3.5 project for disciplines of excellence Clinical Research Incubation Project, West China Hospital, Sichuan University [grant number 2019HXFH008].

Author information

Author notes

  1. Qingqing Jia and Jibo Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China

    Qingqing Jia, Jibo Sun, Dongguang Wang, Xiu Li, Shijie Zhang, Lian Wang, Sitong Liu, Xiang Tong & Hong Fan

  2. State Key Laboratory of Respiratory Health and Multimorbidity, Chengdu, 610041, China

    Qingqing Jia, Jibo Sun, Dongguang Wang, Xiu Li, Shijie Zhang, Lian Wang, Sitong Liu, Xiang Tong & Hong Fan

  3. West China Hospital, General Practice Medical Center, Sichuan University, Chengdu, 610041, China

    Jiao Xu

Authors
  1. Qingqing Jia
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  2. Jibo Sun
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  3. Dongguang Wang
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  4. Jiao Xu
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  5. Xiu Li
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  6. Shijie Zhang
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  7. Lian Wang
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  8. Sitong Liu
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  9. Xiang Tong
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  10. Hong Fan
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Contributions

QQ. Jia decided and executed the search strategies, and was a major contributor in writing the manuscript. JB. Sun, ST. Liu, J. Xu, and X. Li participated in literature retrieval, assessment, and screening. L. Wang contributed to data entry, processing, and analysis. DG. Wang was involved in the creation of figures and tables. SJ. Zhang contributed to manuscript drafting and revision. X. Tong and H. Fan conducted the final review of the manuscript. QQ. Jia and JB. Sun contributed equally to this work. All authors were involved in designing and conducting the study as well as writing and proofing the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiang Tong or Hong Fan.

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Jia, Q., Sun, J., Wang, D. et al. Clinical features and prognostic predictors of C. Psittaci Pneumonia: a systematic review and individual patient meta-analysis. BMC Pulm Med 25, 55 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03511-5

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03511-5

Keywords

BMC Pulmonary Medicine

ISSN: 1471-2466

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