Introduction
Chlamydia psittaci is a gram-negative, obligate intracellular bacterium. Infection by
C. psittaci is transmitted to human beings mainly through contact or inhalation of aerosol, feces, or feather dust from nasal secretions of infected birds [
1‐
3]. The primary host of
C. psittaci is various birds including parrots and pigeons. In addition, mammals and poultry are potential hosts of the bacterium and can readily transmit it to people [
1‐
3].
C. psittaci infection in humans is mainly an occupational infection. Moreover, person-to-person transmission has been reported, however, it is extremely rare [
4‐
7].
C. psittaci mainly causes respiratory and digestive tract diseases in birds. In humans, it causes respiratory tract infection and bacteremia.
C. psittaci pneumonia is prevalent among adults and rare in children, accounting for approximately 1% of all community-acquired pneumonia [
8]. The disease has an incubation period of five to fourteen days [
9]. It mainly invades the lungs, liver, spleen, meninges, and central nervous system. The main symptoms of pneumonia caused by
C. psittaci include fever (body temperatures above 38.5 ℃), headache, myalgia, cough, and dyspnea.
C. psittaci can be manifested as asymptomatic to mild infection, resulting in systemic multiple organ dysfunction, severe pneumonia, and may result in death [
10‐
13].
Diagnostic methods currently used for
C. psittaci include pathogen culture, serological detection, and molecular biology techniques including polymerase chain reaction (PCR). Diagnosis of
C. psittaci pneumonia is challenging in early stages owing to its atypical clinical manifestations. The low sensitivity and complex procedure of
Chlamydia psittaci culture causes it hardly routinely performed in most diagnostic laboratories. Other laboratory testing included serological assay and polymerase chain reaction (PCR) based methods, but both have questionable sensitivity and specificity. Metagenomic next-generation sequencing technology (mNGS) can detect various pathogenic microorganisms without bias through sequencing and analysis of microorganisms as well as host nuclear acid in clinical samples. Rapid screening of pathogens facilitates timely identification of pathogens to initiate targeted antibiotic treatment. Therefore, mNGS has been gradually applied in clinical practice in recent years [
14,
15]. A total of 13 cases of severe pneumonia caused by
C. psittaci diagnosed using mNGS method in Dongyang Hospital Affiliated to Wenzhou Medical University are presented in the current study.
Discussion
Psittacine commonly known as parrots are the main hosts of
C. psittaci. In addition, birds and commercial poultry are potential hosts of
C. psittaci and can transmit the disease to humans. Contact with infected birds, feathers, tissues, or corpses of birds, and cleaning of contaminated cages predisposes individuals to
C. psittaci infection [
9,
17,
18].
C. psittaci infection can be caused by short-term contact with birds or their excreta, and activities that do not involve direct contact with excreta including mowing or pruning [
19,
20].
C. psittaci pneumonia accounts for appoximately 1% of all community-acquired pneumonia [
8]. The mortality rate of
C. psittaci pneumonia was 15–20% before the era of antibiotics [
21]. Notably, the mortality rate has significantly decreased with the advent and development of targeted antibiotics.
Diagnosis of C. psittaci pneumonia is challenging owing to its atypical clinical manifestations. For instance, a few patients may not have a history of bird contact. Patients are commonly treated for common community-acquired pneumonia when clinicians do not carefully collect medical history or if the patients report lack of contact history. Furthermore, detection of C. psittaci is not often included in the scope of routine detection, resulting in misdiagnosis. In addition, several patients visit the hospital at an early stage of the disease and are mainly treated with empirical antibiotics owing to the hierarchical diagnosis and treatment system. Moreover, the disease has a self-limiting nature. These factors potentially lead to underestimation of the incidence rate of Chlamydia pneumonia.
Main clinical manifestations of
C. psittaci pneumonia include fever, chills, headache, general discomfort, and myalgia. In addition, patients may present with a dry cough and progressive dyspnea or chest tightness. Moreover, a pulse temperature dissociation (rarely without increased pulse rate), splenomegaly, or nonspecific rash observed in patients. Furthermore,
C. psittaci is associated with several extrapulmonary manifestations, including endocarditis, myocarditis, hepatitis, arthritis, keratoconjunctivitis, encephalitis, and ocular adnexal lymphoma [
22‐
24]. Pulmonary auscultation is ineffective and often inconsistent with severe clinical manifestations. Laboratory analysis shows that the white blood cell count in patients with
C. psittaci pneumonia is significantly lower compared with other pneumonia types [
25]. In the current study, the average white blood cell count was normal, however, the CRP levels were significantly higher compared with the normal value. This finding is consistent with findings from other studies. The major imaging manifestations include consolidation of the air cavity, ground glass shadow, grid shadow, small patches and nodules, pleural effusion, and lobular distribution, with manifestation highly common in the lower lobes of lungs [
24,
26]. Multiple image forms may coexist, indicating that the disease gradually develops from bronchioles to surrounding lobules and overlaps with each other. In the present study, five cases showed manifestation of the disease in the upper lobe, whereas eight cases presented distribution in the lower lobe.
Positive diagnosis of
C. psittaci requires at least one of the following tests: (1) Isolation of
C. psittaci from respiratory tract specimens; (2) Antibody titer of double serum is 4-fold higher or more compared with the normal value as shown by complement binding test (CFT) or micro immunofluorescence (MIF); relative titer of IgM of
C. psittaci detected by MIF method is more than 1:16. Notably, only a few microbiological laboratories have facilities for conducting these tests. Microbiological culture is time-consuming, and requires a P3 containment laboratory [
9]. Polymerase chain reaction (PCR) is used for quick identification of acute and asymptomatic patients and helps identify the source of disease through genotyping. Notably, sensitivity of PCR is higher in the acute stage of the disease, whereas sensitivity rapidly decreases with progression of the disease. In addition, not all laboratories have facilities for performing PCR analysis. The serological detection method is limited by cross-reaction with other
Chlamydia strains. It is used for detection of the bacteria in serum samples of patients in acute and convalescent stages. Therefore, serological detection method is only suitable for retrospective diagnosis and can be used for epidemiological investigation [
27]. Notably, each detection method has its limitations, including low sensitivity, cross-reactivity with related species and inefficiency in collecting the optimal clinical specimens at the optimal time intervals for subsequent tests. Therefore, detection is often performed through combination of various laboratory detection methods. Moreover, there is no a “gold standard” method for diagnosis [
28] resulting in low diagnosis rates.
C. psittaci infection among elderly patients is more severe compared with infection with pneumonia caused by other
Chlamydia strains, and the course of disease spans several weeks. Studies report that
C. psittaci caused outbreaks in several places in Europe such as Belgium and Netherlands in the past [
29,
30], thus the impact of the disease on human beings cannot be underestimated. Moreover, there is an urgent need for convenient, rapid, and accurate detection methods to ensure timely and effective treatment.
All patients in the current study were diagnosed through mNGS after presenting with no improvement after antibiotic treatment. Notably, mNGS accurately detects pathogens in patients with unexplained lower respiratory tract infection and the results can be obtained within 48–72 h. The number of pathogen sequences detected by mNGS in BALF was more compared with that in sputum. Notably, there was no interference with oral colonization bacteria implying that it used as the preferred sample. mNGS method is characterized by timely and accurate detection of pathogens. Therefore, mNGS helps in facilitating timely and targeted treatment in clinical setups. Moreover, it effectively shortens the diagnosis time of the disease, mainly for patients with severe pneumonia caused by C. psittaci, thus presenting a significant diagnostic value.
Tetracycline is the first-line treatment option for
C. psittaci pneumonia. However, macrolides can be used if tetracyclines are contraindicated (in children, pregnant women, or allergies). In some cases, quinolones are effective, however, they are less effective compared with tetracycline and macrolides [
31]. In the current study, four cases were initially treated with quinolones. However, the therapy was not effective thus the treatment was changed to tetracycline drugs, and finally, the patients recovered and were discharged. Targeted antibiotic treatment decreases
C. psittaci pneumonia mortality to less than 1%. The mortality rate can reach 10–20% if inappropriate treatment is used [
29]. Symptoms are rapidly alleviated with one-two days after administration of targeted antibiotics, and the treatment should be continued for at least fourteen days [
29]. Hospitalized patients with severe community acquired pneumonia (CAP) may require intravenous administration with a combination of tetracycline and quinolones [
29].
The main limitation of this study is that it was retrospective in nature and included only thirteen cases presenting with severe psittacosis pneumonia. The relatively small sample size is insufficient to explore all relevant features of psittacosis pneumonia. A prospective study of severe psittacosis pneumonia is ongoing, to further explored the feature of the disease and to explore effective therapies.
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