Psittacosis

Article Author:
Justin Chu
Article Editor:
Muhammad Durrani
Updated:
2/19/2019 10:41:31 AM
PubMed Link:
Psittacosis

Introduction

Psittacosis represents a zoonotic bacterial infectious disease caused by the obligate intracellular organism, Chlamydia psittaci. Psittacosis, which is also called parrot fever and ornithosis, is transmitted from contact with infected birds and causes a wide-ranging spectrum of disease and severity. Birds serve as the major epidemiological reservoir and while birds from the order Psittaciformes (parakeets, parrots, lories, cockatoos, and budgerigars) and Galliformes (chickens, turkeys, pheasants) are commonly identified, this disease process can occur in any bird species and has been documented in 467 species from 30 different orders of birds.[1] Thus, the major risk factor is bird exposure with human transmission occurring by direct contact with infected birds, or through inhalational routes via aerosolized organisms in feces, urine, respiratory and eye secretions. Human-to-human transmission, while possible, is believed to be a rare event.[1]

Etiology

C. psittaci are gram-negative, obligate intracellular bacteria of both mammals and birds with multiple genotypes which can be sequenced by genotype-specific real-time PCR for identification and epidemiological studies. Each genotype is associated with a specific animal host, and all can be transmitted to humans possibly causing psittacosis.[1]

Epidemiology

Psittacosis can affect any age group and gender, but incidence tends to peak in middle age, with an age range of 35 to 55.[2] The first outbreak of psittacosis linked the disease to pet parrots and finches in 1879, with pandemics occurring in 1929 and 1930. Despite this, psittacosis is regarded as a rare zoonotic infection. Thus, there is a decreased awareness of this disease entity among the public as well as health care professionals, and when coupled with the need for specialized testing, underdiagnosis of psittacosis is likely when examining true reports of psittacosis’ prevalence and incidence.[3] The Centers for Disease Control and Prevention (CDC), in the United States, classifies psittacosis as a reportable condition in most states with estimated confirmed cases numbering fewer than 10 annually. Most experts attribute this to underdiagnosis and underreporting. Since psittacosis is largely described in instances of close contact with birds, certain individuals are considered at higher risk for contracting this disease. This includes individuals with exposure to pet shops, veterinary hospitals, bird exhibitions, and occupational exposure in the poultry industry.[3] Sporadic outbreaks of psittacosis have occurred in the United States secondary to occupational exposure, with the most recent outbreak being 13 confirmed cases in Georgia and Virginia in 2018.

Another study examining the incidence of psittacosis in the United States concluded that during the years of 1999 to 2006, the reported cases of psittacosis varied between 12 and 25 annually, indicating an incidence of 0.01 per 100,000 population.[4] Studies that have examined hospitalized patients with pneumonia have found psittacosis being the etiology of pneumonia in less than 5% of cases.[5][6] Per the CDC, there has been a decline in reported psittacosis cases since 1988.

Pathophysiology

Although the exact pathophysiology has yet to be fully elucidated, recent studies using a bovine model show that upon inoculation of C. psittaci to the host, there is an initial infection of the alveolar epithelial cells.[7] Following the natural course of this infection, there is a multiplication of the bacterium within the host’s epithelial cells allowing for its virulence and spread. This initiates a complex host response leading to a large influx of neutrophils, thought to be mediated through chemokine release, especially interleukin-8, a pro-inflammatory cytokine, from the infected host.[7] This acute phase reaction mediated through chemokines leads to activation of an inflammatory cascade and reactive oxygen species, which triggers further recruitment and accumulation of phagocytes and immune cells from the bloodstream to the site of the infection. This is thought to result in tissue damage and breakdown of the alveolar-capillary membrane enabling the hematogenous spread of C. psittaci.[7] The localized infection and resulting inflammatory cascade also result in a relative barrier for oxygen transfer within the alveoli leading to hypoxemia as well as limitations in lung compliance and resultant alveolar hypoventilation.[7]

Histopathology

C. psittaci are gram-negative, obligate intracellular bacteria with a developmental cycle that entails two forms. The organism consists of an extracellular infectious elementary body and a larger metabolically active intracellular reticulate body. After exposure to a host’s eukaryotic cell, the infectious, elementary body is endocytosed into the cell through interaction with the cell membrane receptor of the host cell, thereby evading the host immune system response. The endocytosed elementary body increases in size to form the metabolically active reticulate body.[8][9] These reticulate bodies can undergo binary fission utilizing ATP from the host cell to form new reticulate bodies. These inclusion reticulate bodies then restructure back into an intermediate state and finally into elementary bodies and are released by cell lysis as well as reverse endocytosis, which can leave the host cell intact, and is thought to allow a chronic and silent infection.[9] These released elementary bodies then infect new host cells and propagate the disease cycle and can spread via the hematogenous route to various organ systems.[10]

History and Physical

Despite the strong link to bird exposure, it is not necessary for a diagnosis. This is especially true in areas with large numbers of wild birds. For example, there have been two outbreaks in Australia with towns surrounded by a large avian flora.[11][12] Regardless, a large part of the diagnosis relies on a thorough history with regards to the patient’s medical history, occupation, hobbies, travel history, as well as a high index of suspicion. Symptoms of psittacosis are mainly respiratory in humans, but clinical symptoms can vary tremendously. After replication in the respiratory system, the infection can spread hematogenous to affect multiple organ systems. It is often described initially as an influenza-like syndrome characterized by fevers, chills, headache, and a cough. Case studies have shown that despite this, the infection can range from an asymptomatic state to a fulminant invasive disease with an average incubation period of 5 to 14 days.[13]

Symptom onset is typically abrupt, with a headache cited as the most prominent complaint in addition to fever, myalgias, nausea, vomiting, diarrhea, and cough.[2] Studies have cited the presence of a severe headache as being a characteristic feature, with consideration of meningitis in the differential diagnosis given its severity.[1] Other signs of psittacosis that have been documented include altered mental status, mild neck stiffness, photophobia, hepatosplenomegaly, and pharyngitis.[1]

Psittacosis can affect multiple different organ systems and manifestations reported in the literature are listed below:

  • Central nervous system manifestations including meningoencephalitis, cerebellar ataxia, cranial nerve palsies, transverse myelitis, Guillain-Barre syndrome, and status epileptics[1]
  • Respiratory manifestations include pneumonia, acute respiratory distress syndrome, respiratory failure, and septic shock[1]
  • Cardiac manifestations include myocarditis, pericarditis, culture-negative endocarditis, and aortitis[1]
  • Renal and gastrointestinal manifestations include acute interstitial nephritis, acute renal failure, glomerulonephritis, hepatitis, pancreatitis, as well as acute abdomen prompting exploratory laparotomy[1]
  • Hematological manifestations include disseminated intravascular coagulation (DIC), splenomegaly, and hemophagocytic syndrome[1]
  • Rheumatological manifestations include reactive arthritis and polyarteritis[1]
  • There have also been cases of gestational psittacosis with poor fetal and maternal outcomes, as well as an association with ocular lymphoma.[1]

Evaluation

In the appropriate clinical scenario with signs and symptoms consistent with psittacosis, the clinician should consider laboratory workup and imaging. Laboratory workup may show a normal to slightly lowered white blood cell count initially during the acute phase of the illness with noted leukopenia later in the disease course.[14] Anemia has also been observed, most commonly attributed to hemolysis.[14] Liver function testing, specifically aspartate and alanine aminotransferase, as well as gamma-glutamyl transpeptidase (AST, ALT, GGT) have also been shown to be variably elevated in psittacosis.[14] Additionally, C-reactive protein (CRP) is variable elevated as well in case studies.[14]

Regarding imaging, it has been noted that the chest x-ray is abnormal in up to 80% to 90% of hospitalized patients, showing a wide range of findings. These include unilateral consolidation to bilateral, miliary, interstitial and nodular infiltrates.[1][14] It should be noted that a normal chest x-ray does not rule out psittacosis.

The CDC has published guidelines for the diagnosis of psittacosis. In the appropriate clinical scenario, a diagnosis is made by meeting any one of the criteria listed below:

  1. Isolation of the causative organism from respiratory secretions
  2. A noted four-fold or greater increase in antibody titer between serum samples collected 2 weeks apart via the complement-fixation test (CFT) or micro-immunofluorescence (MIF)
  3. A single IgM antibody titer detected by MIF of 1:16 or higher

It should be noted that isolation of C. psittaci culture during the acute infection is the most reliable diagnostic test, but it is not recommended as it requires a biosafety level three facility due to the risk of transmission, and thus, is rarely performed.

Treatment / Management

Treatment for this bacterial infection is based on intracellular activity, pharmacokinetics, and evidence from clinical trials which recommend tetracycline antibiotics, particularly doxycycline in the individual without contraindications. Case studies have shown that with treatment, most infected individuals will have an improvement in fever and clinical symptoms by 48 hours.[2] In cases where oral antibiotics cannot be used, intravenous doxycycline can still be used. The treatment with doxycycline uses 100 mg orally or intravenously every 12 hours for 10 to 14 days.

In pregnancy and in patients where doxycycline is contraindicated, the infection is best treated with macrolide antibiotics, such as azithromycin and erythromycin for a 7-day course.

Third line antibiotics active against C. psittaci include fluoroquinolones, which are less effective than tetracyclines and macrolides.

Differential Diagnosis

The differential diagnosis includes atypical pneumonias such as mycoplasma pneumonia, legionella pneumonia, as well as entities such as Q fever (Coxiella burnetii), Tularemia (Francisella tularenis), and influenza.

Prognosis

The prognosis of psittacosis will depend on the patient’s clinical disease severity, co-morbid conditions, as well as the time of treatment and supportive care. Despite antibiotic treatment, it is estimated that the mortality rate is 1%.[15]

Complications

Patients infected with psittacosis can present with many different manifestations owing to its hematogenous spread after initial inoculation. Please refer to the “History and Physical” section above for a thorough outline of different complications. In short, complications of infection with C. psittaci include severe pulmonary complications including pneumonia, ARDS, respiratory failure, as well as endocarditis, myocarditis, sepsis, DIC, meningoencephalitis, hepatitis, and pancreatitis; rarely the patient may present with a fulminant disease course characterized by multi-organ failure.

Deterrence and Patient Education

Per the CDC, isolation precautions and contact prophylaxis are not indicated, as the rates of person-to-person transmission are exceedingly rare. However, in the United States, most states classify psittacosis as a reportable condition. Timely diagnosis aims to control the spread of this disease.

Patients and the public, in general, should be educated on the purchase, handling, and cleaning of birds and birdcages to control the acquisition and spread of disease better. Birds suspected of as a source of infection should be referred to veterinarian and health department personnel.

Pearls and Other Issues

  • Psittacosis is caused the bacterium C. psittaci and is a zoonotic infection mostly attributed to contact with birds.
  • Diagnosis hinges on the clinician performing a thorough patient interview, asking about occupational history, hobbies, travel history, as well as maintaining a high index of suspicion.
  • Most infected individuals present with an influenza-like illness characterized by fevers, chills, myalgias, and a cough, but the presence of a severe headache and gastrointestinal symptoms in the appropriate clinical setting may clue the clinician into the diagnosis.
  • Laboratory testing is largely non-specific but may reveal elevated liver function testing, anemia, and leukopenia, and the chest x-ray is noted to be abnormal in 80% to 90% of cases of hospitalized psittacosis.
  • Diagnosis is clinical but can be confirmed with serological testing as outlined by the CDC.
  • Treatment is with tetracyclines, such as doxycycline, with macrolides being utilized in those with contraindications to tetracyclines.

Enhancing Healthcare Team Outcomes

In 2017, the National Association of State Public Health Veterinarians compiled a compendium on measures to control C. psittaci infection with recommendations being assigned a level of evidence using United States Preventive Services Task Force (USPSTF) framework. They note that secondary to the limitations of psittacosis surveillance, there should be a close relationship between healthcare personnel and public health authorities early in the differential diagnosis to discuss diagnostic options and care.[16] They recommend that those persons at risk, as well as healthcare providers, be educated on the signs, symptoms, and appropriate workup of the disease.[16] (Level B). This should include a public education component outlining proper bird handling, use of protective clothing, and use of a disposable particulate respirator when applicable.[16] (Level B). A combined public health department and healthcare personnel coordinated effort should be undertaken to educate the public and the industry on maintaining accurate records of all bird-related transactions to help with identifying sources of infection.[16] (Level B). The level A evidence-based recommendations noted include the quarantine of exposed birds and isolation of ill birds with signs of psittacosis as well as the use of appropriate disinfection measures on all exposed surfaces.[16] (Level A). These recommendations all stress that a coordinated effort that utilizes healthcare personnel, as well as public health officials, veterinarians, coupled with a public education initiative, is the best way to go about educating and controlling this disease.


References

[1] Stewardson AJ,Grayson ML, Psittacosis. Infectious disease clinics of North America. 2010 Mar;     [PubMed PMID: 20171542]
[2] Yung AP,Grayson ML, Psittacosis--a review of 135 cases. The Medical journal of Australia. 1988 Mar 7;     [PubMed PMID: 3343952]
[3] de Gier B,Hogerwerf L,Dijkstra F,van der Hoek W, Disease burden of psittacosis in the Netherlands. Epidemiology and infection. 2018 Feb;     [PubMed PMID: 29361998]
[4] McNabb SJ,Jajosky RA,Hall-Baker PA,Adams DA,Sharp P,Anderson WJ,Javier AJ,Jones GJ,Nitschke DA,Worshams CA,Richard RA Jr, Summary of notifiable diseases --- United States, 2005. MMWR. Morbidity and mortality weekly report. 2007 Mar 30;     [PubMed PMID: 17392681]
[5] Charles PG,Whitby M,Fuller AJ,Stirling R,Wright AA,Korman TM,Holmes PW,Christiansen KJ,Waterer GW,Pierce RJ,Mayall BC,Armstrong JG,Catton MG,Nimmo GR,Johnson B,Hooy M,Grayson ML, The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2008 May 15;     [PubMed PMID: 18419484]
[6] Berntsson E,Blomberg J,Lagergård T,Trollfors B, Etiology of community-acquired pneumonia in patients requiring hospitalization. European journal of clinical microbiology. 1985 Jun;     [PubMed PMID: 4018066]
[7] Knittler MR,Berndt A,Böcker S,Dutow P,Hänel F,Heuer D,Kägebein D,Klos A,Koch S,Liebler-Tenorio E,Ostermann C,Reinhold P,Saluz HP,Schöfl G,Sehnert P,Sachse K, Chlamydia psittaci: new insights into genomic diversity, clinical pathology, host-pathogen interaction and anti-bacterial immunity. International journal of medical microbiology : IJMM. 2014 Oct;     [PubMed PMID: 25082204]
[8] Grimes JE, Zoonoses acquired from pet birds. The Veterinary clinics of North America. Small animal practice. 1987 Jan;     [PubMed PMID: 3551306]
[9] Peeling RW,Brunham RC, Chlamydiae as pathogens: new species and new issues. Emerging infectious diseases. 1996 Oct-Dec;     [PubMed PMID: 8969247]
[10] Vanrompay D,Ducatelle R,Haesebrouck F, Chlamydia psittaci infections: a review with emphasis on avian chlamydiosis. Veterinary microbiology. 1995 Jul;     [PubMed PMID: 7571380]
[11] Williams J,Tallis G,Dalton C,Ng S,Beaton S,Catton M,Elliott J,Carnie J, Community outbreak of psittacosis in a rural Australian town. Lancet (London, England). 1998 Jun 6;     [PubMed PMID: 9734887]
[12] Telfer BL,Moberley SA,Hort KP,Branley JM,Dwyer DE,Muscatello DJ,Correll PK,England J,McAnulty JM, Probable psittacosis outbreak linked to wild birds. Emerging infectious diseases. 2005 Mar;     [PubMed PMID: 15757553]
[13] Beeckman DS,Vanrompay DC, Zoonotic Chlamydophila psittaci infections from a clinical perspective. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2009 Jan;     [PubMed PMID: 19220335]
[14] Longbottom D,Coulter LJ, Animal chlamydioses and zoonotic implications. Journal of comparative pathology. 2003 May;     [PubMed PMID: 12834606]
[15] Hogerwerf L,DE Gier B,Baan B,VAN DER Hoek W, Chlamydia psittaci (psittacosis) as a cause of community-acquired pneumonia: a systematic review and meta-analysis. Epidemiology and infection. 2017 Nov;     [PubMed PMID: 28946931]
[16] Balsamo G,Maxted AM,Midla JW,Murphy JM,Wohrle R,Edling TM,Fish PH,Flammer K,Hyde D,Kutty PK,Kobayashi M,Helm B,Oiulfstad B,Ritchie BW,Stobierski MG,Ehnert K,Tully TN Jr, Compendium of Measures to Control Chlamydia psittaci Infection Among Humans (Psittacosis) and Pet Birds (Avian Chlamydiosis), 2017. Journal of avian medicine and surgery. 2017 Sep;     [PubMed PMID: 28891690]