Co-infection of COVID-19 patients with atypical bacteria: A study based in Jordan.

Objective: The aim of this work was to know the prevalence of Chlamydophila pneumoniae and Mycoplasma pneumoniae in coronavirus disease 2019 (COVID-19) patients in Jordan. Also, to assess a TaqMan real-time polymerase chain reaction (PCR) assay in detecting these two bacteria. Methods: This is a retrospective study performed over the last five months of the 2021. All nasopharyngeal specimens from COVID-19 patients were tested for C. pneumonia, and M. pneumoniae. The C. pneumoniae Pst-1 gene and M. pneumoniae P1 cytadhesin protein gene were the targets. Results: In this study, 14 out of 175 individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (8.0%) were co-infected with C. pneumoniae or M. pneumoniae. Co-infection with SARS-CoV-2 and C. pneumoniae was reported in 5 (2.9%) patients, while 9 (5.1%) patients had M. pneumoniae and SARS-CoV-2 co-infection. The mean (± std) of the correlation coefficient of the calibration curve for real-time PCR analysis was -0.993 (± 0.001) for C. pneumoniae and -0.994 (± 0.003) for M. pneumoniae. The mean amplification efficiencies of C. pneumoniae and M. Pneumoniae were 187.62% and 136.86%, respectively. Conclusion: In this first study based in Jordan, patients infected with COVID-19 have a low rate of atypical bacterial co-infection. However, clinicians should suspect co-infections with both common and uncommon bacteria in COVID-19 patients. Large prospective investigations are needed to give additional insight on the true prevalence of these co-infections and their impact on the clinical course of COVID-19 patients.

Effect of Past Chlamydophila pneumoniae Infection on the Short-Time Mortality of COVID-19: A Retrospective Cohort Study.

BACKGROUND: Although Chlamydophila pneumoniae (CP)is known to play a role in atherosclerosis and endothelial injury, its past infection on the mortality of coronavirus disease 2019 (COVID-19), which was also reported to be a vascular disease, remains unknown. METHODS: In this retrospective cohort study, we examined 78 COVID-19 patients and 32 bacterial pneumonia patients who visited a tertiary emergency center in Japan between April 1, 2021, and April 30, 2022. CP antibody levels, including IgM, IgG, and IgA, were measured. RESULTS: Among all patients, the CP IgA-positive rate was significantly associated with age (P = 0.002). Between the COVID-19 and non-COVID-19 groups, no difference in the positive rate for both CP IgG and IgA was observed (P = 1.00 and 0.51, respectively). The mean age and proportion of males were significantly higher in the IgA-positive group than in the IgA-negative group (60.7 vs. 75.5, P = 0.001; 61.5% vs. 85.0%, P = 0.019, respectively). Smoking and dead outcomes were significantly higher both in the IgA-positive group and IgG-positive group (smoking: 26.7% vs. 62.2, P = 0.003; 34.7% vs. 73.1%, P = 0.002, dead outcome: 6.5% vs. 29.8%, P = 0.020; 13.5% vs. 34.6%, P = 0.039, respectively). Although the log-rank test revealed higher 30-day mortality in the IgG-positive group compared to the IgG-negative group (P = 0.032), Cox regression analysis demonstrated no significant difference between the IgG-positive and negative groups (hazard ratio (HR) = 4.10, 95%CI = 0.94-18.0, P = 0.061). CONCLUSION: The effect of past CP infection on 30-day mortality in COVID-19 patients was not obvious.

Co-infection of COVID-19 patients with atypical bacteria: A study based in Jordan

Objective: The aim of this work was to know the prevalence of Chlamydophila pneumoniae and Mycoplasma pneumoniae in coronavirus disease 2019 (COVID-19) patients in Jordan. Also, to assess a TaqMan real-time polymerase chain reaction (PCR) assay in detecting these two bacteria. Methods: This is a retrospective study performed over the last five months of the 2021. All nasopharyngeal specimens from COVID-19 patients were tested for C. pneumonia, and M. pneumoniae. The C. pneumoniae Pst-1 gene and M. pneumoniae P1 cytadhesin protein gene were the targets. Results: In this study, 14 out of 175 individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (8.0%) were co‐infected with C. pneumoniae or M. pneumoniae. Co‐infection with SARS‐CoV‐2 and C. pneumoniae was reported in 5 (2.9%) patients, while 9 (5.1%) patients had M. pneumoniae and SARS‐CoV‐2 co-infection. The mean (± std) of the correlation coefficient of the calibration curve for real-time PCR analysis was –0.993 (± 0.001) for C. pneumoniae and –0.994 (± 0.003) for M. pneumoniae. The mean amplification efficiencies of C. pneumoniae and M. Pneumoniae were 187.62% and 136.86%, respectively. Conclusion: In this first study based in Jordan, patients infected with COVID-19 have a low rate of atypical bacterial co-infection. However, clinicians should suspect co-infections with both common and uncommon bacteria in COVID-19 patients. Large prospective investigations are needed to give additional insight on the true prevalence of these co-infections and their impact on the clinical course of COVID-19 patients. (AU)

An Algorithm for the Selection of Probes for Specific Detection of Human Disease Pathogens Using the DNA Microarray Technology.

The aim of the study was to develop an algorithm for the selection of discriminating probes to identify a wide range of causative agents of human infectious diseases. Materials and Methods: The algorithm for selecting the probes was implemented in the form of the disprose (DIScrimination PRObe SElection) computer program written in the R language. Additionally, third-party software was used: the BLAST+ and ViennaRNA Package programs. The developed algorithm was tested by selecting specific probes for detecting Chlamydophila (Chlamydia) pneumoniae - an atypical bacterial pathogen causing community-acquired pneumonia (CAP). Nucleotide sequences for analysis were downloaded from the NCBI databank. Results: An algorithm for the selection of specific probes capable of detecting human infectious pathogens has been developed. The algorithm is implemented in the form of the disprose modular program, which allows for performing all stages of the probe selection process: loading the nucleotide sequences and their metadata from available databanks, creating local databases, forming a pool of probes, calculating their physicochemical parameters, aligning the probes and sequences contained in local databases, processing and evaluating the alignment results. The algorithm was successfully tested and its performance was confirmed by selecting a set of probes for the specific detection of Chlamydophila pneumoniae. The specificity of the selected probes calculated in silico indicated a low risk of their nonspecific binding and a high potential of using them as molecular genetic diagnostic tools (DNA microarrays, PCR). Conclusion: An algorithm for the selection of specific probes detecting a wide range of human pathogens in clinical biomaterial has been developed and implemented in the form of the disprose modular program. The probes selected using this program can serve as the functional basis of DNA-oriented microarrays able to identify causative agents of polyetiological diseases, such as CAP. Due to the flexibility and openness of the program, the scope of its application can be expanded.

Gestational Antibodies to C. pneumoniae, H. pylori and CMV in Women with Preeclampsia and in Matched Controls.

OBJECTIVES: Some research has suggested a possible role for past infection in the development of preeclampsia. The objective of this study was to explore the role of Helicobacter pylori, cytomegalovirus, and Chlamydophila pneumoniae in the development of preeclampsia in a prospective pregnancy sample. METHODS: We conducted a nested case-control study in The Archive for Child Health (ARCH), a pregnancy cohort of 867 unselected women enrolled at the first prenatal visit with archived blood and urine in pregnancy. We matched 21 cases of preeclampsia to 52 unaffected controls on maternal age (±4 years), race, parity, and gestational age at blood draw. Using conditional logistic regression, we examined the association between preeclampsia status and immunoglobulins G (IgG) tested by indirect ELISA to each of the three microorganisms, adjusting for potential confounders. RESULTS: No significant difference was found between cases and controls. The unadjusted odds ratio was 1.5 (95%CI: 0.2-9.1), 0.6 (95%CI: 0.2-1.9), and 1.9 (95%CI: 0.6-5.6) for H. pylori, cytomegalovirus and C. pneumoniae respectively. After controlling for confounders analysis found increased odds of H. pylori IgG (AOR: 1.9; 95% CI: 0.2-15.3) and C. pneumoniae IgG (AOR: 2.3; 95% CI: 0.6-9.2) for preeclampsia, albeit being not significant. Conversely, cytomegalovirus IgG had lower odds for preeclampsia (AOR: 0.4; 95% CI: 0.1-1.7). CONCLUSIONS: Past infection with H. pylori, and C. pneumoniae in early pregnancy showed a higher risk of preeclampsia, but the findings failed to achieve statistical significance. Cytomegalovirus was not associated with preeclampsia in these data. These preliminary findings encourage future research in populations with high prevalence of these infections.

Mucosal Respiratory Syndrome: A Systematic Literature Review.

BACKGROUND: Mycoplasma pneumoniae atypical pneumonia is frequently associated with erythema multiforme. Occasionally, a mycoplasma infection does not trigger any cutaneous but exclusively mucosal lesions. The term mucosal respiratory syndrome is employed to denote the latter condition. Available reviews do not address the possible association of mucosal respiratory syndrome with further atypical bacterial pathogens such as Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella species. We therefore performed a systematic review of the literature addressing this issue in the National Library of Medicine, Excerpta Medica, and Web of Science databases. SUMMARY: We found 63 patients (≤18 years, n = 36; >18 years, n = 27; 54 males and 9 females) affected by a mucosal respiratory syndrome. Fifty-three cases were temporally associated with a M. pneumoniae and 5 with a C. pneumoniae infection. No cases temporally associated with C. psittaci, C. burnetii, F. tularensis, or Legionella species infection were found. Two cases were temporally associated with Epstein-Barr virus or influenzavirus B, respectively.

Clinical characteristics of Chlamydia psittaci pneumonia: an analysis of 13 cases / 中华全科医师杂志

Objective:To analyze the clinical characteristics of pneumonia caused by Chlamydia psittaci (C. psitttaci). Methods:A retrospective analysis was performed on the clinical data of 13 consecutive patients with C. psitttaci pneumonia admitted to the First Affiliated Hospital of Xiamen University from November 2018 to February 2021. Results:All 13 cases had symptoms of fatigue and 6 cases had headache. At consultation, the ΔSequential Organ Failure Assessment (SOFA) scores of all patients were ≥2 points. According to the Pneumonia Severity Index (PSI) score, 2 patients were grade Ⅱ and the other 11 patients were grade Ⅳ or Ⅴ. Laboratory tests showed that C-reactive protein (CRP) and procalcitonin (PCT) levels were elevated in all patients; CRP≥100 mg/L was found in 11 cases and PCT≥0.5 ng/ml was found in 9 cases.There were 12 cases with respiratory failure and 12 cases with elevated transaminase. Chest CT scans showed multiple patchy exudative shadow, focal consolidation and air bronchial sign; and the lesions were mainly in the lower lungs (8 cases). C. psitttaci infections were confirmed by metagenomics next-generation sequencing (mNGS) and the patients′ conditions improved rapidly after timely adjustment of doxycycline based drug treatment and active organ support. The lesions were completely absorbed without residual fibrous cord changes and the prognosis was good. Conclusions:Pneumonia caused by C. psitttaci usually presents sepsis, and the disease progresses rapidly. The mNGS is of value for the early diagnosis of C. psitttaci pneumonia. Timely adjustment of antibiotics treatment after etiological diagnosis can lead to a good prognosis.

One Joint Aspirate: Three Diagnoses.

Gout is a frequently diagnosed condition. However, it is rarely diagnosed with concomitant pseudogout or reactive arthritis (ReA) from ​​​​​Chlamydophila pneumoniae (C. pneumoniae). This case report describes an interesting case of a 67-year-old man who presented with a two-week history of malaise, chills, and shortness of breath. He also reported a one-day history of polyarthritis, which limited his ambulation. The results of polarized microscopy revealed uric acid and calcium pyrophosphate crystals. The respiratory panel was positive for C. pneumoniae and rhinovirus. Therefore, he was diagnosed with gout, pseudogout, and ReA. Appropriate management led to a full clinical recovery. This is the first report documenting the simultaneous occurrence of ReA, gout, and pseudogout in a single patient. The association between these rheumatic diseases and a summary of similar cases in the literature are also discussed.

Association of Chlamydophila pneumoniae infection and hypertension during pregnancy - A case control study.

BACKGROUND: The association of Chlamydophila pneumoniae infection with essential hypertension is known but its association with hypertension during pregnancy is controversial. Hence, this study aimed to explore the association of C. pneumoniae infection with hypertension during pregnancy. The objectives were to compare the presence of C. pneumoniae DNA in trophoblastic cells of placenta between hypertensive and normotensive pregnant women and to find out the presence of inflammatory marker (HSP-60) and the seropositivity (IgG and IgA) of C. pneumoniae in them. MATERIALS AND METHODS: The study was conducted at a tertiary-care institute, in South-India between 2018 and 2020. Women with hypertension during pregnancy were study group (75) and normotensive pregnant women were control group (75). IgG and IgA antibodies, HSP-60 against C. pneumoniae were estimated by ELISA from 5 ml of venous blood. C. pneumoniae DNA was extracted from placental tissue after delivery and tested by RT-PCR. STATISTICAL ANALYSIS: The association between C. pneumoniae DNA, seropositivity and hypertension was determined by student test and univariate regression analysis. RESULTS: C. pneumoniae DNA was detected in the placenta of 29.3% with hypertension and none in controls and the odds was 6.5 (OR-6.5, CI 95%). HSP-60 was elevated in women with preeclampsia and not in gestational hypertension and controls. IgA was not detected and IgG was positive in 15.2% of women with preeclampsia. CONCLUSION: There is a significant association between C. pneumoniae infection and hypertension during pregnancy and further studies are required to fulfil the Koch's postulates to prove or disprove it as a causative agent.

Plasma Amyloid-ß in Relation to Antibodies Against Herpes Simplex Virus, Cytomegalovirus, and Chlamydophila pneumoniae.

BACKGROUND: Amyloid-ß (Aß), the key constituent of Alzheimer's disease (AD) plaques, has antimicrobial properties. OBJECTIVE: To investigate the association between plasma Aß and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae. METHODS: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aß40 and Aß42 concentrations with Luminex xMAP technology and INNOBIA plasma Aß-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases. RESULTS: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aß42 or Aß40 in cases or controls. CONCLUSION: Levels of plasma Aß were not associated with antibodies against different AD-related pathogens.

Atypical Bacterial Pathogens and Small-Vessel Leukocytoclastic Vasculitis of the Skin in Children: Systematic Literature Review.

Leukocytoclastic small-vessel vasculitis of the skin (with or without systemic involvement) is often preceded by infections such as common cold, tonsillopharyngitis, or otitis media. Our purpose was to document pediatric (≤18 years) cases preceded by a symptomatic disease caused by an atypical bacterial pathogen. We performed a literature search following the Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines. We retained 19 reports including 22 cases (13 females and 9 males, 1.0 to 17, median 6.3 years of age) associated with a Mycoplasma pneumoniae infection. We did not find any case linked to Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella pneumophila. Patients with a systemic vasculitis (N = 14) and with a skin-limited (N = 8) vasculitis did not significantly differ with respect to gender and age. The time to recovery was ≤12 weeks in all patients with this information. In conclusion, a cutaneous small-vessel vasculitis with or without systemic involvement may occur in childhood after an infection caused by the atypical bacterial pathogen Mycoplasma pneumoniae. The clinical picture and the course of cases preceded by recognized triggers and by this atypical pathogen are indistinguishable.

Rash and Mucositis Associated With Mycoplasma pneumoniae and Chlamydophila pneumoniae: A Recurrence of MIRM?

INTRODUCTION: A new concept has come to light recently, that is, Mycoplasma-induced rash and mucositis (MIRM). Here, we report the first case of recurrent rash, mucositis, and conjunctivitis involving Mycoplasma pneumoniae and C. pneumoniae that fits under the criteria of what is currently defined as MIRM. CASE PRESENTATION: A patient aged 12 years with a history of recurrent aphthous ulcers presented in 2013 with worsening oral lesions, conjunctivitis, and vesicular rash. Her respiratory polymerase chain reaction (PCR) panel was positive for M. pneumoniae. She was diagnosed with Stevens-Johnson syndrome (SJS) secondary to M. pneumoniae and treated with a macrolide, acyclovir, and intravenous immunoglobulin (IVIG). The same patient returned 3 years later with an identical constellation of symptoms, at which time her PCR was positive for C. pneumoniae. In addition to IVIG and a macrolide, a corticosteroid treatment was administered. DISCUSSION: Here, we present the case of a pediatric patient with a recurrence of mucocutaneous disease that is more consistent with MIRM than the proposed SJS or erythema multiforme (EM) documented via histology. Our patient's symptoms were controlled with azithromycin and IVIG and, in the second episode, with corticosteroids as well. This case adds to that of Mayor-Ibarguren et al, providing further evidence that C. pneumonia may also be a trigger for MIRM. Patients will benefit from expanding the definition of MIRM, as the pathogenesis differs from SJS and EM and could result in more specific treatment options.

Skin and Mucous Membrane Eruptions Associated with Chlamydophila Pneumoniae Respiratory Infections: Literature Review.

BACKGROUND: Mycoplasma pneumoniae pneumonia is sometimes associated with skin or mucous membrane eruptions. Available reviews do not address the association of Chlamydophila pneumoniae pneumonia with skin eruptions. We therefore conducted a systematic review of the literature addressing this issue. The National Library of Medicine, Excerpta Medica, and Web of Science databases were employed. SUMMARY: In two reports, skin lesions and especially urticaria were more common (p < 0.05) in atypical pneumonia caused by C. pneumoniae as compared with M. pneumoniae. We found 47 patients (<18 years, n = 16; ≥18 years, n = 31) affected by a C. pneumoniae atypical pneumonia, which was associated with erythema nodosum, erythema multiforme minus, erythema multiforme majus, isolated mucositis, or cutaneous vasculitis. We also found the case of a boy with C. pneumoniae pneumonia and acute generalized exanthematous pustulosis. We did not find any case of C. pneumoniae respiratory infection associated with either Gianotti-Crosti syndrome, pityriasis lichenoides et varioliformis acuta Mucha-Habermann, or varicella-like skin eruptions.

Physicians' prediction for the assessment of atypical pathogens in respiratory tract infections.

BACKGROUND: Patients with acute respiratory tract infections are frequently prescribed antimicrobials despite high rates of virus detection. Physicians may overprescribe antimicrobials owing to the concern of bacterial infections, including those because of atypical pathogens. We investigated the accuracy of clinical predictions concerning atypical pathogen infections. METHODS: We prospectively enrolled adult patients who presented with a fever and cough in outpatient clinics between December 2016 and August 2018. After taking a history and performing physical examinations, physicians predicted the possibility of respiratory infections because of atypical pathogens. Disease probabilities were categorized into 3 grades (high: ≥50%, intermediate: 20% ≥ and <50%, and low: <20%) and were judged by physicians who were taking care of the patients. Confirmation of atypical pathogens was performed by comprehensive molecular analyses of respiratory samples. RESULTS: Atypical pathogens were detected in 21 of 210 patients. A close contact history (odds ratio [OR]: 11.4, 95% confidence interval [CI]: 2.4-53.5) and the presence of pneumonia (OR: 12.9, CI: 4.3-39.2) were associated with the detections. Atypical pathogens were detected in 32.3% of high-probability cases (10/31), while atypical pathogens were only detected in 8.8% of intermediate-probability cases (8/91) and 3.4% of low-probability cases (3/88) (P < .001). CONCLUSIONS: The current study indicates that physicians' predictions were associated with the detection of atypical pathogens; however, overestimation was observed.

Alzheimer's disease - the 'microbial hypothesis' from a clinical and neuroimaging perspective.

The etiology of Alzheimer's disease (AD) is under debate since its first description in 1906. Extracellular senile plaques composed of beta-amyloid peptide (Aß) and intracellular neurofibrillary tangles composed of tau protein characterize the histopathology of the disease. The 'amyloid cascade hypothesis' summarizes the molecular mechanisms leading to deposition of these proteins. However, treatments derived from this hypothesis have been unsuccessful. An infectious etiology for AD has been repeatedly proposed. Neurotropic viruses, gut and lung bacteriae, and Bovine Meat and Milk Factors have been implicated in neurodegenerative disorders including AD. These pathogens may act directly or as a trigger or co-factor for inducing neurodegeneration in AD. The antimicrobial properties of beta-amyloid have shifted the discussion of the etiological origin of AD towards an interaction hypothesis. Neuroimaging studies have added to the understanding of mechanisms involved in neurodegeneration. Antiviral agents and a bacterial protease inhibitor targeting Porphyromonas gingivalis toxins are currently tested in clinical trials. Further clinical studies are needed to test if strategies directly derived from the 'microbial hypothesis' or combination strategies including antimicrobial agents may be beneficial for patients with Alzheimer's disease.

Diagnostic utility of serology and polymerase chain reaction for detection of Mycoplasma pneumoniae and Chlamydophila pneumoniae in paediatric community-acquired lower respiratory tract infections.

Purpose: Mycoplasma pneumoniae (M. pneumoniae) and Chlamydophila pneumoniae (C. pneumoniae) play a significant role in children of all ages with lower respiratory tract infections (LRTIs). This study was conducted to detect M. pneumoniae and C. pneumoniae in children with community-acquired LRTIs employing serology, polymerase chain reaction (PCR) and nested PCR analysis. Material and Methods: This study included 75 children with acute LRTIs for detection of M. pneumoniae and C. pneumoniae. Blood was obtained for M. pneumoniae and C. pneumoniae antibodies and nasopharyngeal aspirates for M. pneumoniae PCR and C. pneumoniae nested PCR. Results: M. pneumoniae infection was positive in 9 (64.21%) children aged 2-6 months and in 5 (35.79%) aged 7 months-12 years, and this difference was statistically significant (P = 0.002). C. pneumoniae infection was comparable within the age group and statistically insignificant (P = 0.43). Clinical and radiological profiles of M. pneumoniae- and C. pneumoniae-positive and negative patients were numerically comparable. Serology and PCR together detected M. pneumoniae infection in 14 (18.6%) children. The sensitivity, specificity and positive and negative predictive values of serology were 77.78%, 92.42%, 58.33% and 96.83%, respectively. C. pneumoniae infection was positive in 11 (14.6%) children by serology and nested PCR with 50% sensitivity, 87.67% specificity, 10% positive predictive value and 98.46% negative predictive value. Conclusions: Our study confirms that M. pneumoniae and C. pneumoniae play a significant role in community-acquired LRTIs and a combination of serology and nested PCR is useful for its diagnosis.

Where is Chlamydophila pneumoniae pneumonia?

BACKGROUND: Molecular diagnostic methods have recently gained widespread use, and consequently, the importance of viral pathogens in community-acquired pneumonia (CAP) has undergone re-evaluation. Under these circumstances, the role of Chlamydophila pneumoniae as a pathogen that causes CAP also needs to be reviewed. METHODS: We reviewed articles that contained data on the frequency of identification of C. pneumoniae pneumonia as a causative pathogen for CAP. The articles were identified by performing a search in PubMed with the keywords "community-acquired pneumonia" and "pathogen". RESULTS: Sixty-three articles were identified. The reviewed articles demonstrated that the rates of identification of C. pneumoniae as the causative pathogen for CAP were significantly lower in assessments based on polymerase chain reaction (PCR) methods than in those based on serological methods. In some studies, it was possible to compare both serological and PCR methods directly using the same set of samples. CONCLUSIONS: The use of PCR methods, including multiplex PCR assays, has revealed that C. pneumoniae may play a limited role as a pathogen for CAP.