Animal sources for zoonotic transmission of psittacosis: a systematic review

Psittacosis is a zoonosis caused by the bacterium Chlamydia (C.) psittaci. Transmission occurs mainly by inhalation of the agent, which is excreted by birds in feces and in droplets from the respiratory tract [1, 2]. In the 1930s, major outbreaks of psittacosis occurred worldwide, caused by trade of parrots and other tropical birds. These outbreaks are even referred to as ‘the psittacosis pandemic’ [3‐5]. In 1985, an outbreak of psittacosis affected employees at a duck processing plant in the United Kingdom [6]. Nowadays psittacosis cases are usually limited to local outbreaks, small clusters or isolated cases [7‐17]. Community-acquired pneumonia (CAP) is the most important presentation of human psittacosis, but microbiological testing for psittacosis in a pneumonia patient is often not incorporated in routine diagnostics. Due to the non-specific symptoms and the fact that often only severely ill patients are being tested for C. psittaci, the disease is likely underdiagnosed and underreported [18‐22]. A recent review and meta-analysis of CAP etiological studies estimated that in 1.03% (95% CI: 0.79–1.30) of all CAP cases from the included studies combined, C. psittaci was the causative pathogen, with a range between studies from 0 to 6.7% [21]. Based on this result, an estimated 4.4% (95% CI: 1.6–8.2%) of symptomatic cases were notified in the Netherlands over the period 2012–2014 [20]. Human psittacosis is mostly linked to parrots or ornamental birds as source of infection, however, recently other bird and animal species have been gaining more attention as potential sources of human psittacosis, such as poultry species, pigeons and even mammals [23‐26]. To inform clinicians, public health officials and people at risk of exposure to potentially infected animals, we reviewed animal sources that have been associated with human psittacosis in the recent international literature and provided strength of evidence for zoonotic transmission for each of the animal categories.

Psittaciformes still remain an important source of human psittacosis, as almost one-third of the included zoonotic associations included in this review reported on psittaciformes, however, the overall strength of evidence was low. A possible explanation for our finding that the evidence for psittaciformes is relatively weak could be that clinicians and public health officials consider contact of a pneumonia patient with a parrot-like bird as sufficient evidence for psittacosis and for starting presumptive antibiotic treatment. The fact that psittacine birds are generally accepted as source of C. psittaci also introduces publication bias, as systematic research is performed to a lesser extent. However, when several human cases are involved and a thorough source trace-back investigation is performed, evidence for zoonotic transmission from psittaciformes can be very strong [42, 65].

In contrast, physicians might disregard turkeys and other poultry species as a source for zoonotic transmission of C. psittaci. ‘Natural immunity’, due to continuous exposure, has been suggested for individuals who are regularly in close contact with poultry, because in some studies most of the C. psittaci culture- and PCR-positive poultry workers did not present with any clinical signs [45, 46]. Contrastingly, Lagae et al. found that 25 out of 29 C. psittaci PCR-positive poultry farmers reported symptoms possibly related to psittacosis [73]. Since genotypes A, C and D found by Dickx et al. [46] were identical to those described by Lagae et al. [73], it is less likely that the difference between symptomatic and asymptomatic infections can be attributed to a difference in genotype. The diverging findings show that more research into asymptomatic infection and natural immunity of human psittacosis related to poultry is required.

A genotypical match between human and animal samples has been documented for chickens, columbiformes, ducks, geese, guinea fowl, passeriformes, peacock, psittaciformes, strigiformes and turkeys. Host specificity of genotypes has been described, with genotype A being mostly linked to psittacine birds, B and E to pigeons, D and E to turkeys, and C and E/B to ducks [1, 75]. Generally, these patterns of host specificity are also found in the genotypical matches summarized in this review, but exceptions are present. In turkeys, for example, genotypical matches were very divergent, as matches were also reported for the genotypes A, C and E/B, which are generally more specific for psittacine birds and ducks. Detection of a specific genotype in a human psittacosis case can give a direction for the possible animal source. However, during source tracing, also the non-genotype-host specific animal sources need to be kept in mind. Furthermore, this ‘macro’ level of genotype matching to confirm animal-human transmission has its limitations, as strain identity is less accurately defined compared to whole genome sequencing.

Results from this review also indicate the possibility of mammals being a source of C. psittaci infection to humans, but the strength of evidence for zoonotic transmission for these mammalian species was relatively low. The outbreak of three psittacosis cases in a veterinary school linked to exposure to infected fetal membranes of a mare did have a maximum score of 15 [37]. This could indicate a novel source of infection, but genotyping was only performed on the animal sample.

There are several reports of occurrence of C. psittaci in mammalian species [97‐102]. However, this occurrence is often attributed to transmission from birds to mammals [100, 101, 103]. This was also suggested in the article describing zoonotic transmission from a mare, as it seemed feasible that the mare contracted the bacterium from wild birds in the surrounding area. This might indicate that mammalian species are not the reservoir of the disease, but act as an intermediate species in the transmission to humans. Nevertheless, it is important to further investigate transmission dynamics of C. psittaci within and between animal populations, as animal-to-animal transmission of a bovine isolate of C. psittaci in calves has been reported [104]. The possibility of zoonotic transmission from non-avian animals should be further investigated. Moreover, there has been evidence for human-to-human transmission of C. psittaci [10, 105, 106].

Recently, a C. psittaci related species named C. gallinaceae has been added to the family of Chlamydiaceae [107], with chickens and turkeys as the predominant hosts. Hulin et al. investigated the presence of C. psittaci as well as C. gallinaceae in poultry. They found a high prevalence of C. gallinaceae in a slaughterhouse where chickens, guinea fowls and turkeys were processed [68]. Human cases related to other species than C. psittaci were not included in this review, however, the high prevalence of C. gallinaceae in poultry indicates the need to assess the zoonotic potential of this relatively unknown species.

This review has some limitations. Although we included multiple languages in our search strategy, the geographical spread of articles included in our review is limited, as the majority of studies is from the European region. A relatively large number of studies originated from Belgium, the Netherlands and France, and these predominantly investigated poultry. This may reflect a particular interest in psittacosis related to poultry among researchers from these countries. Partly, this could be due to the fact that psittacosis in poultry is a notifiable disease in Belgium [108], however, not in the Netherlands and France.

We did not qualitatively review the study design of the included articles, as the majority of the included articles were case studies. This type of study design is considered of low quality and reliability. Data extraction was also difficult, as the description of human cases and animal sources was relatively poor in some studies. However, we did always extract the data according the original authors rationale.

In fifteen studies, human cases were described with multiple associated animal sources. The aim of this review was to give an overview of all associated animal sources. Therefore, in case of multiple exposures, the animal sources were entered into separate lines under the same study, which causes human cases to be entered twice. Moreover, when multiple animals are associated, it could be that for some animal species the suspicion of being the actual source of infection is low, but are included in the investigation for certainty, which can cause bias towards a lower evidence score for these animal sources.

The strength of evidence score is based on a self-developed scoring system, in which a weight was assigned to each factor included in the calculation. The subjectivity of the weights influences the strength of evidence score. With a weight of 8, the factor ‘genotypical match’ had a high impact on the final strength of evidence scores. As the genotype matching was made on a ‘macro’ level, a score of 8 is disputable. When assigning a weight of 4 to this factor, as means of a sensitivity analysis, the boxplot summary scores are lower, but the general pattern and conclusion between animal categories remain stable. For transparency, all the raw data and a flexible strength of evidence calculation tool have been included in Additional file 2. This allows the reader to manually adjust the weights and interpret the effects on the individual strength of evidence scores, as well as on the boxplot summary scores for the different animal categories.

The included studies showed a wide variety in tests used to confirm a case, e.g. PCR, serology, culture or combinations. Even between studies, that reported to use PCR, discrepancies were present, as the applied PCR methods varied in amplification techniques, specificity and DNA targets. Also the type of serological test applied (e.g. Enzyme-Linked Immunosorbent Assay, immunofluorescence, complement fixation test) differed. Apart from antigen and/or antibody testing, the specific type of test and the corresponding sensitivity or specificity values of these tests were not taken into account in our review, meaning that the reliability of the number of confirmed individuals varies per study included. We maintained the number of cases as stated in the original article, because some articles did not mention a case definition, and other articles differed too much in sampling methods and type of test to distinguish between case definitions. This broad range of tests and criteria for case confirmations is in line with the main findings of a review by Nieuwenhuizen et al. on laboratory methods for case finding in human psittacosis outbreaks [14]. They concluded that there is no standard or uniformity in tests used to confirm human cases. In general, exposure assessment in most studies was rather weak, mostly lacking specification of the chronology of events. We therefore reported ‘contact with sick animals’ irrespective of when exactly the animals became ill. People can also become infected after contact with asymptomatic animals [109], but sick animals are likely to shed more bacteria, thus having a higher chance of transmission, which is why contact with sick animals was assigned a higher weight. However, asymptomatic animals may pose a higher threat to public health because they are less evident as a source and may cause more delay in diagnosing the disease in humans.