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Rationale: Psittacosis, also known as parrot fever, is an infectious disease caused by Chlamydia psittaci, which can lead to C psittaci pneumonia. Clinical manifestations are highly nonspecific, which can vary from asymptomatic infection to severe pneumonia and even death., Patient Concerns: In this case presentation, we reported one 65-year-old male case of C psittaci pneumonia who was admitted to our hospital on December 2, 2022 due to the chief complaints of poor appetite and fatigue for 3 days as the clinical manifestations. He denied contact with birds but admitted riding horses 1 week ago., Diagnoses: Chlamydia psittaci pneumonia of patient was confirmed through metagenomic sequencing of bronchoalveolar lavage fluid under bronchoscopy., Intervention: Patient was treated with V-V ECMO, invasive mechanical ventilation and CRRT., Outcomes: On December 12, the patient was successfully weaned off V-V ECMO and discharged on December 20, 2022. During postoperative follow-up, CT scan in a local hospital revealed the infiltrative lesions of the lung were absent., Lessons: This case prompts that metagenomic next-generation sequencing is a feasible diagnostic tool for psittacosis, which can rapidly worsen and even cause sudden cardiac arrest. V-V ECMO might be a viable emergency therapeutic option., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Clinical Data: Chlamydia psittaci pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. While severe cases may lead to critical conditions such as respiratory failure, splenic infarction is relatively uncommon. A severe patient with Chlamydia psittaci pneumonia admitted to our hospital experienced a splenic infarction during treatment. Fortunately, the patient's situation was improved after careful treatment. Now, the patient has been discharged. Further exploration of the mechanism of concurrent splenic infarction is required., Backgroud: Psittacosis pneumonia, a zoonotic infectious disease transmitted from birds to humans, is caused by Chlamydia psittaci and represents a type of chlamydial pneumonia [1]. Insome instances, the disease may progress to severe pneumonia and respiratory failure, necessitating intensive support measures, including mechanical ventilation. The advent of technologies such as Metagenomic Next-Generation Sequencing (mNGS) for the etiological diagnosis of infectious diseases [2] has improved the diagnostic and treatment success rates for Psittacosis. Instances of severe chlamydial pneumonia with complications such as splenic infarction are uncommon. A patient with severe Psittacosis pneumonia complicated by splenic infarction was admitted to the Emergency Intensive Care Unit (EICU) of Haining People's Hospital and subsequently improved following effective anti-infective and anticoagulant therapy. This report is provided herein., (© 2024. The Author(s).)

This study presents the clinical profile of a 74-year-old male patient admitted to the hospital due to a 20-day history of coughing, chest tightness, and dyspnea. Upon admission, the patient presented with fever, tachycardia, and tachypnea. Clinical examination revealed evidence of lung infection, sepsis, and multi-organ dysfunction, alongside abnormal blood gas analysis and elevated C-reactive protein (CRP) levels. Pathogen testing confirmed Chlamydia psittaci (C. psittaci), infection. Throughout the treatment course, the patient developed concurrent fungal and viral infections, necessitating a comprehensive approach involving combined antibiotic and antifungal therapy. Despite encountering treatment-related complications, the patient demonstrated clinical improvement with aggressive management. This case underscores the importance of recognizing immune suppression subsequent to Chlamydia infection, emphasizing the critical role of early diagnosis, intervention, and standardized treatment protocols in enhancing patient prognosis., (© 2024. The Author(s).)

Introduction: Dilated cardiomyopathy (DCM) is characterized by the enlargement of the left ventricle or biventricular, accompanied by myocardial systolic dysfunction. Chlamydia psittacosis (CP) is a zoonotic pathogen, which can cause severe pneumonia, respiratory failure, and acute organ dysfunction. The deterioration of DCM caused by CP infection is extremely rare, and few cases of successful management were reported., Case Presentation: We reported a 67-year-old male patient with DCM and chronic heart failure. Who was admitted to ICU with severe pneumonia, acute hypoxemic respiratory failure, acute decompensated heart failure, arrhythmia, and cardiogenic shock. Mechanical ventilation (MV) and venous-arterial extracorporeal membrane oxygenation (VA-ECMO) were established for respiratory and circulatory support. Broncho alveolar lavage fluid(BALF)was collected for culture and metagenomics next-generation sequencing (mNGS) test. Repeated mNGS tests indicated the high possibility of CP pneumonia, thereafter, moxifloxacin and doxycycline were prescribed. After targeted antibiotics and organ support treatment, pneumonia, respiratory and circulatory failure were gradually resolved, patient was successfully weaned from MV and VA-ECMO. Finally, the patient was recovered and discharged alive., Conclusions: Severe respiratory and circulatory failure caused by CP infection in DCM patients is a rare life-threatening clinical condition. Early accurate diagnosis, targeted antibiotic therapy, coupled with extracorporeal life support posed positive impact on the patient's disease course and outcome., (© 2023. The Author(s).)

Background: Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND)., Case Presentation: A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum., Conclusions: The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment., (© 2023. The Author(s).)

Introduction: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF)., Methods: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods., Results: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO 2 /FiO 2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline., Conclusion: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis), also known as parrot disease, parrot fever, and ornithosis, is a zoonotic bacterial disease. Humans most often become infected by inhaling the organism when urine, respiratory secretions, or dried feces of infected birds are dispersed in the air as very fine droplets or dust particles. C. psittaci infection of humans can cause influenza-like symptoms, such as fever of abrupt onset, pronounced headache, and dry cough, and can lead to severe pneumonia and non-respiratory health problems. Infection can also be asymptomatic. There is no vaccine for this infection. The disease is treatable with a tetracycline antibiotic, usually doxycycline, or a second-line therapy such as erythromycin or azithromycin. With appropriate treatment, the infection is rarely fatal. This report describes a case of severe, community-acquired pneumonia possibly due to C. psittaci in a resident of Colorado and examines significant clinical and epidemiological characteristics of psittacosis that affect confirming the diagnosis and managing the risks of exposure to psittacine (parrot-type) birds.

Since 2007, most areas of China have seen outbreaks of poultry airsacculitis, which causes hugely economic losses to the poultry industry. However, there are no effective measures to combat the problem. In this study, 105 rations were collected to isolate Aspergillus spp. from the diseased farms. In subsequent experiments, SPF chickens were inoculated with Ornithobacterium rhinotracheale (ORT), Chlamydia psittaci (C. psittaci) and Aspergillus fumigatus (A. fumigatus), and mortality rate, body weight gain and lesion score were evaluated. Of these ration samples, 63 (60.0%) were A. fumigates, 21 (20.0%) were Aspergillus niger (A. niger) and 11 (10.5%) were Aspergillus candidus (A. candidus). Furthermore, SPF birds infected with C. psittaci, ORT, H9N2 virus and A. fumigatus conidia exhibited a mortality rate of 40%, while simultaneous co-infection with C. psittaci, ORT and A. fumigatus resulted in a mortality rate of 20%. The avian airsacculitis was manifested in the C. psittaci + ORT/A. fumigatus, C. psittaci + H9N2 + ORT/A. fumigatus and C. psittaci + H9N2/A. fumigatus groups while others had transient respiratory diseases without mortality. Our survey indicates that feed-borne A. fumigatus is prevalent in poultry rations. The combination of C. psittaci, ORT, H9N2 and A. fumigatus conidia contributes to the replication of avian airsacculitis by aggravating the severe damage to the air sacs and lungs of chickens.

A 61-year-old man was admitted with a 1-week history of influenza-like symptoms during a period of increased influenza virus activity. He soon developed type 2 respiratory failure and became increasingly drowsy. He later suffered a convulsive episode in the intensive care unit (ICU) which self-terminated. Initial clinical findings suggested community-acquired pneumonia and meningoencephalitis. However, a detailed history revealed that he was a pet bird-keeper, which raised a suspicion of ornithosis. Chlamydia psittaci DNA was detected in sputum by PCR. He was started on appropriate antibiotics and made a full recovery. We present this uncommon cause of pneumonia as an example of the importance of accurate history-taking to ensure a correct diagnosis for optimal management., (2016 BMJ Publishing Group Ltd.)

Psittacosis is a rare disease particularly in children with usual presentation of respiratory and constitutional symptoms. The cases may remain undiagnosed or diagnosis may be delayed because of lack of awareness among the paediatricians and physicians. Early diagnosis is very important as this is potentially curable and preventable disease. An interesting case of psittacosis is being reported here, which has been treated successfully with azithromycin.

Avian influenza virus subtype H9N2 (H9N2) and Chlamydia psittaci (C. psittaci) are frequently isolated in chickens with respiratory disease. However, their roles in co-infection remain unclear. We tested the hypothesis that C. psittaci enhances H9N2 infection through suppression of host immunity. Thus, 10-day-old SPF chickens were inoculated intra-tracheally with a high or low virulence C. psittaci strain, and were simultaneously vaccinated against Newcastle disease virus (NDV). Significant decreases in body weight, NDV antibodies and immune organ indices occurred in birds with the virulent C. psittaci infection, while the ratio of CD4+/CD8+ T cells increased significantly compared to that of the lower virulence strain. A second group of birds were inoculated with C. psittaci and H9N2 simultaneously (C. psittaci+H9N2), C. psittaci 3 days prior to H9N2 (C. psittaci/H9N2), or 3 days after H9N2 (H9N2/C. psittaci), C. psittaci or H9N2 alone. Survival rates were 65%, 80% and 90% in the C. psittaci/H9N2, C. psittaci+H9N2 and H9N2/C. psittaci groups, respectively and respiratory clinical signs, lower expression of pro-inflammatory cytokines and higher pathogen loads were found in both C. psittaci/H9N2 and C. psittaci+H9N2 groups. Hence, virulent C. psittaci infection suppresses immune response by inhibiting humoral responses and altering Th1/Th2 balance, increasing mortality in H9N2 infected birds.

Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 7% to 8% of newly diagnosed lymphomas. Because of its association with infectious causes, such as Helicobacter pylori (HP) or Chlamydophila psittaci (CP), and autoimmune diseases, it has become the paradigm of an antigen-driven malignancy. MALT lymphoma usually displays an indolent course, and watch-and-wait strategies are justified initially in a certain percentage of patients. In patients with gastric MALT lymphoma or ocular adnexal MALT lymphoma, antibiotic therapy against HP or CP, respectively, is the first-line management of choice, resulting in lymphoma response rates from 75% to 80% after HP eradication and from 33% to 65% after antibiotic therapy for CP. In patients who have localized disease that is refractory to antibiotics, radiation is widely applied in various centers with excellent local control, whereas systemic therapies are increasingly being applied, at least in Europe, because of the potentially systemic nature of the disease. Therefore, the objective of this review is to briefly summarize the clinicopathologic characteristics of this distinct type of lymphoma along with current data on management strategies., (© 2015 American Cancer Society.)

Purpose: To compare genome-wide DNA methylation profiles according to Chlamydophila psittaci (Cp) infection status and the response to doxycycline treatment in Korean patients with ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL)., Methods: Twelve ocular adnexal EMZL cases were classified into two groups (six Cp-positive cases and six Cp-negative cases). Among the 12 cases, eight were treated with doxycycline as first-line therapy, and they were divided into two groups according to their response to the treatment (four doxy-responders and four doxy-nonresponders). The differences in the DNA methylation states of 27,578 methylation sites in 14,000 genes were evaluated using Illumina bead assay technology. We also validated the top-ranking differentially methylated genes (DMGs) with bisulfite direct sequencing or pyrosequencing., Results: The Infinium methylation chip assay revealed 180 DMGs in the Cp-positive group (74 hypermethylated genes and 106 hypomethylated genes) compared to the Cp-negative group. Among the 180 DMGs, DUSP22, which had two significantly hypomethylated loci, was validated, and the correlation was significant for one CpG site (Spearman coefficient=0.6478, p=0.0262). Regarding the response to doxycycline treatment, a total of 778 DMGs were revealed (389 hypermethylated genes and 336 hypomethylated genes in the doxy-responder group). In a subsequent replication study for representative hypomethylated (IRAK1) and hypermethylated (CXCL6) genes, the correlation between the bead chip analysis and pyrosequencing was significant (Spearman coefficient=0.8961 and 0.7619, respectively, p<0.05)., Conclusions: Ocular adnexal EMZL showed distinct methylation patterns according to Cp infection and the response to doxycycline treatment in this genome-wide methylation study. Among the candidate genes, DUSP22 has a methylation status that was likely attributable to Cp infection. Our data also suggest that the methylation statuses of IRAK1 and CXCL6 may reflect the response to doxycycline treatment.

Chlamydia (C.) psittaci is the causative agent of psittacosis, a zoonotic disease in birds and man. In addition, C. psittaci has been repeatedly found in domestic animals and is, at least in calves, also able to induce respiratory disease. Knowledge about transmission routes in cattle herds is still deficient, and nothing is known about differences in host response after either experimental or natural exposure to C. psittaci. Therefore, our recently developed respiratory infection model was exploited to evaluate (i) the presence of the pathogen in blood, excretions and air, (ii) the possibility of transmission and (iii) clinical symptoms, acute phase and immune response until 5 weeks after exposure. In this prospective study, intrabronchial inoculation of 10(8) inclusion-forming units of C. psittaci (n = 21 calves) led to reproducible acute respiratory illness (of approximately one week), accompanied by a systemic inflammatory reaction with an innate immune response dominated by neutrophils. Excretion and/or exhalation of the pathogen was sufficient to transmit the infection to naïve sentinel calves (n = 3) co-housed with the infected animals. Sentinel calves developed mild to subclinical infections only. Notably, excretion of the pathogen, predominantly via feces, occurred more frequently in animals naturally exposed to C. psittaci (i.e. sentinels) as compared to experimentally-inoculated calves. The humoral immune response was generally weak, and did not emerge regularly following experimental infection; however, it was largely absent after naturally acquired infection.

Purpose: We investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in ocular adnexal lymphoma (OAL) and the possible association with clinical characteristics and Chlamydophila psittaci infection., Methods: Thirty-five cases of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma cases were examined for the methylation status of nine genes using methylation-specific PCR and for the detection of C. psittaci DNA using PCR. The medical records were reviewed retrospectively. Patient demographics, clinical characteristics including the response of the lymphoma to the therapy, and C. psittaci infection status were evaluated for possible association with methylation frequencies., Results: CpG island methylation in nine genes was variously found as follows; DAPK (94.3%), ECAD (77.1%), MT1G (48.6%), THBS1 (37.1%), RAR-β (31.4%), p16 (20%), MGMT (5.7%), p14 (0%), and RASSF1A (0%). Methylation was not observed in any of 13 control cases. C. psittaci DNA was observed in 25 (75.8%) of 33 patients with available tumor tissues, and ECAD hypermethylation was significantly higher in C. psittaci-positive cases (P = 0.041). Promoter hypermethylation status was not correlated with clinical characteristics., Conclusions: Aberrant CpG island methylation of tumor suppressor genes is a frequent event in ocular adnexal MALT lymphoma. In particular, high frequencies of DAPK and ECAD methylation may be strongly correlated with ocular adnexal MALT lymphomagenesis in South Korea. Furthermore, ECAD hypermethylation is closely associated with C. psittaci infection, which may shed light on the mechanisms of bacterium-induced oncogenesis.

Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.

This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2-3 months via bronchoscope at four different challenge doses from 10(6) to 10(9) inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 10(6) ifu/calf resulted in a mild respiratory infection only, the doses of 10(7) and 10(8) induced fever, tachypnea, dry cough, and tachycardia that became apparent 2-3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 10(9) ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 10(6) and 10(7) ifu, about 15% in calves inoculated with 10(8) and more than 30% in calves inoculated with 10(9) ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 10(6) or 10(8) ifu/calf of C. psittaci DC15 while doses above 10(8) ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions.

Objectives: Recent evidence indicates that Chlamydophila psittaci (Cp) may establish chronic infections, which may promote autoimmunity and/or B cell lymphoproliferation., Methods: The presence of a subclinical Cp infection was investigated in 293 patients with chronic inflammatory polyarthritis, including 175 patients with rheumatoid factor (RF)-positive and/or anti-CCP-positive rheumatoid arthritis (RA) and 118 with seronegative polyarthritis (46 RF-negative/anti-CCP-negative RA, 36 psoriatic arthritis and 36 undifferentiated spondyloarthritis). One hundred and eighty-five healthy controls were also investigated. The presence of Cp infection was assessed in peripheral blood mononuclear cells using several PCR protocols targeting different regions of the Cp genome (16S-23S spacer rRNA, OMP-A, and Gro-EL). The DNA of other Chlamydia species (C. Pneumoniae and C. Trachomatis) was also investigated. Amplicons were sequenced to confirm the specificity of PCR products., Results: The presence of a subclinical chronic Cp infection was observed in a significantly higher percentage of patients with chronic polyarthritis (38/293; 13%) compared to healthy controls (1/185, 0.5%; OR=27.4, 95%CI:3.73-201.6, p<0.0001). Furthermore, the prevalence of Cp was higher in seronegative polyarthritis (23/118; 19.5%) than in seropositive RA patients (15/175; 7.4%; OR=2.58, 95%CI: 1.28-5.19, p=0.0078). The highest prevalence of Cp infection was found in RF/anti-CCP double-negative RA patients (13/46, 28.3%), followed by patients with psoriatic arthritis (6/36; 16.7%). No differences in age, sex, disease duration and undergoing therapies were noticed between Cp-positive and Cp-negative patients; nor between seropositive and seronegative patients., Conclusions: Cp may be an infectious trigger possibly involved in the pathogenesis of a fraction of inflammatory polyarthritis, particularly in seronegative patients.

A 34-year-old woman with papillary thyroid carcinoma underwent total thyroidectomy with central and lateral lymphadenectomy. Immediate airway compromise required re-intubation immediately after surgery. Marked tracheal and bronchial collapse of greater than 50% of the lumen indicated tracheobronchomalacia. Subsequent attempts at extubation failed over the next week. The patient soon developed evidence of a lower respiratory tract infection. Empirical treatment with penicillins was unsuccessful. A clinical suspicion of chlamydia infection prompted initiation of macrolide treatment followed by resolution of both the patient's respiratory infection and tracheobronchomalacia. Serology returned positive for Chlamydophila psittaci infection. It later transpired that the patient had symptoms of an upper respiratory tract infection just prior to surgery. This case demonstrates an interesting and unreported cause of tracheobronchomalacia as well as providing a good lesson on the importance of preoperative screening for infection.

We report the case of a psittacosis patient with severe abdominal pain who subsequently developed acute respiratory failure. The main symptoms of psittacosis are considered to be upper respiratory inflammation and influenza-like symptoms. However, it should be emphasized that digestive symptoms can be prominent in psittacosis patients. Early diagnosis of this condition is difficult and there is a need for an effective method for rapid diagnosis.

Lymphomas of the ocular adnexa are a heterogeneous group of malignancies, composing approximately 1% to 2% of non-Hodgkin lymphomas (NHLs) and 8% of extranodal lymphomas. The most common subtype, accounting for up to 80% of cases of primary ocular adnexal lymphoma, is marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. In the recent past, there have been significant advances in our understanding of the clinical characteristics, morphology and phenotype, etiology, pathogenesis, diagnosis, natural history, treatment approaches, outcome, and prognostic factors of this disease entity. Novel immunologic and molecular techniques have aided in the distinction between MALT lymphoma and other lymphoproliferative disorders and led to the identification of tissue markers of prognostic significance. Modern imaging modalities provide invaluable tools for accurate staging and treatment planning. Besides radiotherapy and chemotherapy, a variety of new treatment options have emerged in the management of patients with ocular adnexal MALT lymphoma, especially monoclonal antibody therapy and antibiotic therapy against Chlamydia psittaci, which has been associated with the pathogenesis of ocular adnexal lymphomas in some parts of the world. In this review, we present a state-of-the-art summary of ocular adnexal MALT lymphomas.

Ocular adnexal lymphoma (OAL) is a mostly extranodal marginal zone lymphoma (EMZL). Recent findings have suggested an association between Chlamydia psittaci (Cp) infection and OAL. We sought to confirm this issue and to analyze the clinicopathologic characteristics of OAL in Korea. Between 1993 and 2004, 33 OAL cases were identified at the Asan Medical Center, Seoul, Korea. DNA was extracted from paraffin-embedded tissues, and touchdown enzyme time release polymerase chain reaction was performed to identify three Chlamydia species (Cp, C. tracomatis, and C. pneumoniae). The same procedures were also performed in 21 samples from patients with non-neoplastic ocular adnexal disease (NNOAD). All OAL cases were EMZL. Cp DNA was detected in 26/33 (79%) OAL samples compared with 5/21 (23%) NNOAD samples (P < 0.001). With a median follow-up of 38.5 months (range: 1-105 months), the 5-year progression-free survival (PFS) and overall survival (OS) rates of OAL patients were 72% and 93%, respectively. Clinicopathologic characteristics, recurrence rate, PFS, and OS were not associated with Cp infection. Our study demonstrates an association between OAL and Cp infection in Korea, suggesting that Cp plays a role as a causative antigen in Korean OAL patients., (2007 Wiley-Liss, Inc)

Background: An association between ocular adnexal MALT lymphoma (OAL) and Chlamydia psittaci (Cp) infection has been proposed, and recent reports suggest that doxycycline treatment causes tumor regression in patients with Cp-related OAL. The effectiveness of doxycycline treatment in Cp-negative OAL has not been tested., Methods: In a prospective trial, 27 OAL patients (15 newly diagnosed and 12 having experienced relapse) were given a 3-week course of doxycycline therapy. Objective lymphoma response was assessed by computerized tomography scans or magnetic resonance imaging at 1, 3, and 6 months after the conclusion of therapy and every 6 months during follow-up. Cp infection in patients was determined by touchdown enzyme time-release polymerase chain reaction (TETR-PCR). Statistical tests were two-sided., Results: Eleven patients were Cp DNA-positive and 16 were Cp DNA negative. Doxycycline was well tolerated. At a median follow-up of 14 months, lymphoma regression was complete in six patients, and a partial response (> or = 50% reduction of all measurable lesions) was observed in seven patients (overall response rate [complete and partial responses] = 48%). Lymphoma regression was observed in both Cp DNA-positive patients (seven of 11 experienced regression) and Cp DNA-negative patients (six of 16 experienced regression) (64% versus 38%; P = .25, Fisher's exact test). The three patients with regional lymphadenopathies and three of the five patients with bilateral disease achieved objective response. In relapsed patients, response was observed both in previously irradiated and nonirradiated patients. The 2-year failure-free survival rate among the doxycycline-treated patients was 66% (95% confidence interval = 54 to 78), and 20 of the 27 patients were progression free., Conclusions: Doxycycline is a fast, safe, and active therapy for Cp DNA-positive OAL that was effective even in patients with multiple failures involving previously irradiated areas or regional lymphadenopathies. The responses observed in PCR-negative OAL may suggest a need for development of more sensitive methods for Cp detection and investigation of the potential role of other doxycycline-sensitive bacteria.

A recent report suggesting that ocular adnexal non-Hodgkin lymphoma (NHL) may be related to Chlamydia psittaci infection underscores the need for reliable epidemiologic data for this malignancy. We examined population-based incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program. During 1992-2001 in the 12 SEER areas, ocular (i.e., eye and adnexa) NHL rates per 100,000 person-years for both sexes were highest among Asians/Pacific Islanders, lower in whites, and lower still in blacks. Incidence increased with advancing age and showed little difference by sex, in contrast to other (extranodal and nodal) NHLs, which occurred predominantly in males. From 1975-2001, there was a rapid and steady increase in incidence of ocular NHL, with annual increases of 6.2% and 6.5% among white males and females, respectively, with no evidence of peaking. By contrast, other NHLs showed evidence of peaking in recent years. The distinctive patterns of ocular NHL call for further studies to identify risk factors and mechanisms, including the potential role of C. psittaci or other infections.

Background: Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD) and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients., Methods: Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6) or non-alpha-1 antitrypsin deficiency emphysema (n = 34) or wedge resection for hamartochondroma (n = 14) were examined by transmission electron microscopy and PCR., Results: In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR., Conclusions: These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process to a chronic infectious condition. This raises interesting questions on pathogenesis and source of infection.

On a farm housing cattle and goats an abortion storm occurred affecting 50% of the goats during the lambing season 2000/2001. In one of three investigated caprine abortions Chlamydophila abortus could be identified as etiology. During this time a pregnant woman (pregnancy week 19/20) had contact with aborting goats. She developed a severe generalized infection and aborted. The placenta contained Chlamydophila abortus shown by immunohistochemistry and PCR. Aim of the present case report is to alert veterinarians about the potential zoonotic risk of ovine/caprine abortions.

A case of bovine abortion was for the first time in Switzerland diagnosed by immunohistochemistry PCR (16S rRNA, ompA) and gene sequence analysis to be caused by Chlamydia psittaci. A possible occurence of further cases has to be investigated. Based on the existence of several methods with very different sensitivity and specificity to diagnose chlamydia it is suggested that at least two verified diagnostic tools should be used to diagnose an involvement of chlamydia in bovine abortion.

Abortion cases of 144 goats und 86 sheep were investigated etiologically during 2 lambing seasons (1996/1997, 1997/1998). Macroscopic inspection of fetus and placenta was completed by histopathology and bacteriological isolation of agents. In addition, immunohistologically the following antigens were labeled in formalin-fixed and paraffin-embedded tissue sections: Toxoplasma gondii, Neospora caninum, Chlamydophila abortus (formerly Chlamydia psittaci serovar 1) and Border Disease Virus. From farms with abortions caused by Chlamydophila abortus specific data were recorded. In 75% of abortion cases in sheep and in 59% of cases in goats an etiologic diagnosis could be substantiated. Chlamydophila abortus is the most commonly involved agent in the etiology of caprine and ovine abortion (sheep 39%, goats 23%), followed by Toxoplasma gondii (sheep 19%, goats 15%) and Coxiella burnetti (sheep 1%, goats 10%). All other agents are of minor importance. An infectious cause of abortion based on histopathologic findings without isolation of agents was observed in sheep (10%) and goats (21%). Malformation occurred in sheep (2%) and goats (3%) and lesions suggestive for Vitamin E/Selenium deficiency were seen in goats only (2%).

A 29-year-old woman with primary myelofibrosis developed severe pneumonia, and 20 days later her 31-year-old sister also contracted pneumonia. The first patient had been in contact with parakeets but the second patient had not been in contact with any birds. Psittacosis was diagnosed in both cases by microplate immunofluorescence antibody technique. Person-to-person transmission between the sisters was suspected to have taken place.

Two serological tests (indirect immunofluorescence and enzyme-linked immunosorbent assay) were developed for the detection of fetal antibody to Chlamydia psittaci. Fetal blood and thoracic fluid from 126 field cases of suspected ovine chlamydial abortion were examined using both tests. Placenta and fetal tissues (lung, liver, and kidney) from the same animals were also examined by the following conventional diagnostic methods: isolation in McCoy cells, detection of chlamydial lipopolysaccharide (LPS), modified Ziehl-Nielsen staining, and direct fluorescent antibody staining of chlamydia in frozen cryostat sections. Seventy cases were positive by fetal serology, and of these, 68 were also positive by isolation and/or LPS detection. The remaining 56 cases had negative fetal serology, and of these, 39 were positive by isolation and/or LPS detection. Results indicate that fetal serology, although less sensitive than either isolation in McCoy cells or detection of chlamydial LPS antigen, may be of particular use when placenta is not available.

To assess the role of polymorphonuclear neutrophils (PMNs) in Chlamydia psittaci infection in a pregnant mouse model, pregnant and nonpregnant Swiss OF1 mice were depleted of PMNs by treatment with the RB6-8C5 monoclonal antibody before intraperitoneal infection with C. psittaci serotype 1. Nondepleted mice served as infection controls. Depleted mice aborted earlier and had a much higher mortality rate than nondepleted mice. Bacteriological analysis showed that the number of chlamydiae isolated from the spleens of depleted mice at 5 and 7 days postinfection was 100 times greater than that isolated from nondepleted mice. Histopathological analysis of the placentas of depleted mice showed widespread necrosis of the uteroplacental units, with weak immunoreaction to chlamydial antigen, while the placentas of nondepleted mice showed substantial neutrophil infiltration but no large areas of necrosis, with moderate to strong immunoreaction to chlamydial antigen. The livers of depleted mice showed numerous chlamydial inclusions in the hepatocytes, delayed microgranuloma formation, and in the pregnant animals extensive coagulative periportal necrosis. The livers of nondepleted mice displayed multiple small foci of PMNs and mononuclear cells with microgranuloma formation. Among this group of mice, the pregnant animals always had more hepatic damage than nonpregnant animals. Our results suggest that PMNs play an essential role in the response to C. psittaci primary infection, preventing the uncontrolled multiplication of chlamydiae in the liver and spleen.

The anatomical progression of chlamydial infection was studied in different areas of the placenta, using a mouse model and two inoculation times: early pregnancy (day 7, group A) and midpregnancy (day 11, group B). The first population cells affected were decidual cells and neutrophils located just at the limits of the maternal and fetal placenta. The following invaded area was the layer of giant cells. Complete colonization of the maternal placenta occurred after day 15 of pregnancy independently of the inoculation time, the metrial gland being the last area to be invaded; numerous granulated metrial gland (GMG) cells were infected. Finally, chlamydial inclusions were observed in labyrinthine trophoblastic cells from day 18 of pregnancy onward. Since no fetal damage was observed, it seems that an indirect mechanism involving the lysis of GMG cells and neutrophil infiltration of the decidua and metrial gland may be the pathogenic mechanism that leads to abortion.

Enzootic abortion in sheep, caused by Chlamydia psittaci, has been associated with pregnancy failure in most sheep-producing countries. Late-term abortions or the birth of weak low-birth-weight lambs occurred following primary C. psittaci infection in pregnant ewes. However, the mode by which C. psittaci can be transmitted among sheep has not been established. The present study was designed to determine whether the vaginal tracts of nonpregnant ewes were susceptible to C. psittaci infection and whether such infections had an impact during the next pregnancy. At day 0 of the estrus cycle, the vaginal tracts of 10 nonpregnant ewes were inoculated with C. psittaci and 10 ewes were exposed by subcutaneous injection. The ewes were bred 6 weeks postinfection. Five ewes from the vaginally infected group and four from the subcutaneously infected group were reinfected by subcutaneous injection at day 60 of gestation. Pregnancy outcomes and antibody responses to infection were compared with that of ewes that were infected with C. psittaci, either subcutaneously or intravaginally, for the first time during pregnancy and with that of noninfected control ewes. Subcutaneous infection of nonpregnant ewes did not cause subsequent pregnancy failure; rather, this provided protection against abortion following reinfection during pregnancy. As expected, abortions or the birth of weak lambs was observed in those ewes that received primary C. psittaci infection by either route during pregnancy. Similarly, abortion or the birth of weak lambs was a consequence of vaginal inoculation prior to breeding, thereby confirming the susceptibility of the vaginal mucosa to infection and demonstrating the potential for venereal transmission.

Nine aborted fetuses and one newborn calf, diagnosed as Chlamydia psittaci (C. psittaci) infection, were pathologically examined. The characteristic lesions in the liver were focal necrosis in 9 aborted fetuses and granulomatous necrotic foci in the newborn calf. Moderate numbers of intranuclear inclusion bodies were found in necrotic foci of the liver, spleen, thymus, lymph nodes, adrenal gland, kidney, lung and forestomach. Immunohistologically, a small number of C. psittaci antigens was demonstrated in necrotic foci of the liver and correlated with distribution of elementary bodies. Moderate numbers of infectious bovine rhinotracheitis (IBR) virus antigens were also detected in degenerating and necrotizing parenchymal cells in various organs and correlated with distribution of intranuclear inclusion bodies. Thus, these aborted bovine fetuses and newborn calf were interpreted as being dually infected with C. psittaci and IBR virus during pregnancy.

Nineteen ewes were injected subcutaneously with the agent of enzootic ovine abortion, Chlamydia psittaci serovar 1, at 50 days gestation. Placental and fetal tissues were examined at 15 days postinfection and thereafter at ten day intervals. Placental infection was detected at 15 days postinfection. Only postinoculation sera collected from postinfected ewes contained antibodies reactive to C. psittaci. Five (26%) chlamydial infected ewes experienced inapparent fetal loss before day 105 of gestation. This finding is significant since C. psittaci infection in sheep is commonly associated with abortion and not infertility.

A red-tailed hawk (Buteo jamaicensis) with signs of respiratory distress and diarrhea was captured in the Manchac Wildlife Management Area, Louisiana (USA) and died the following day. At necropsy, the carcass was emaciated and there were splenomegaly, and fibrinous pericarditis, airsacculitis, and perihepatitis. Microscopically, there were fibrinous pericarditis and airsacculitis, myocardial necrosis, necrotizing hepatitis, splenic necrosis with reticuloendothelial cell hyperplasia, interstitial pneumonia and focal pancreatic necrosis. Intracytoplasmic chlamydial inclusion bodies were noticed in macrophages in the fibrinous exudate covering air sac and pericardium, and in spleen, liver, heart, lung, and pancreas. Schizonts compatible with a Sarcocystis sp.-like protozoon were present in the walls of air capillaries in the lung. A Chlamydia sp.-like organism was isolated in embryonating chicken eggs and cell culture and identified as C. psittaci with immunofluorescent staining.

A woman in the first trimester of pregnancy presented with pneumonia and hilar lymphadenopathy after exposure to lambing ewes. She subsequently aborted. Infection with Chlamydia psittaci of ovine origin was confirmed. Pregnant women are susceptible to this infection, which may cause life threatening disease. The patient also had features of sarcoidosis, and the two conditions ran a similar time course. There is a possibility that ovine psittacosis caused an illness indistinguishable from sarcoidosis.

Hepatic involvement is considered a rare complication of psittacosis. Occurrence of icteric hepatitis as the cardinal manifestation of the disease has been rarely reported. We describe two members of a family infected by psittacosis, in whom icteric hepatitis was the prominent expression of the disease. The diagnosis of psittacosis was confirmed by isolation of the pathogen and by detection of serum antibodies to Chlamydia species. No serological evidence for acute TWAR infection was found. Chlamydia psittaci was also isolated from the family's parrot.

A previously fit man developed psittacosis with marked cerebellar symptoms and signs. He was febrile but not confused, and he responded rapidly to treatment with erythromycin. Even if respiratory symptoms are minimal, psittacosis and other atypical pneumonias should be considered in any patient presenting with fever and cerebellar involvement.