Pneumocystis: not just pneumonia

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Once known exclusively as the agents of severe pneumonia in immunocompromised individuals, Pneumocystis spp. are now being associated with asymptomatic carriage in hosts that do not have profound immune debilitation. In the absence of a cultivation system, polymerase chain reaction and histological studies have identified Pneumocystis in neonatal populations, in pregnant women and in other patients that have chronic underlying disease processes. These findings in humans and in experimental animal models indicate the presence of potential reservoirs of infection, and provide insights into the transmission of this fungus. Also, the role of Pneumocystis has been investigated as a possible co-morbidity factor.

Introduction

Pneumocystis are fungal organisms that cause pneumonia in immunocompromised hosts [1]. This genus is composed of multiple individual species that require a specific mammalian host — the species that infects humans is named Pneumocystis jirovecii (previously known as Pneumocystis carinii f. sp. hominis) [2]. Experimental approaches for the study of these fungi have been hampered by the lack of an in vitro culture system. Research has relied on animal models of infection as a source of organisms for biochemical testing, drug evaluation and microscopic visualization for life-cycle analyses.

By the increased use of the polymerase chain reaction (PCR) for the study of Pneumocystis, new populations of individuals have become apparent in which detectable Pneumocystis DNA is present, but few or no organisms have been visualized. These observations have provided us with an expanded knowledge of the range of susceptible hosts as well as of the scope of disease. PCR-based detection has enabled previously unanswerable questions about its life cycle and the host–pathogen interactions to be explored.

Many terms, including colonization, carriage, asymptomatic infection and subclinical infection, have been used to describe the presence of Pneumocystis organisms and its DNA in a host without the occurrence of clinical pneumonia. Throughout this article carriage is used, which is defined as the presence of Pneumocystis organisms or DNA in the absence of Pneumocystis pneumonia (PcP). The effects of the presence of a low organism burden on the host have yet to be determined. The role of carriage in mild respiratory infections, chronic lung disease, and progression to PcP are now being actively investigated.

This review focuses on recent developments in the study of Pneumocystis in hosts that, unlike those that have the classically associated disease state of pneumonia, are immunocompetent or only slightly immunocompromised.

Section snippets

Detection methods

Pneumocystis were first detected without the need to visualize the organisms through histochemical staining by the application of PCR methods [3]. Nested PCR protocols soon supplanted standard single-cycle amplification owing to their increased sensitivity. Most PCR-based detection systems employ multi-copy genes such as the mitochondrial ribosomal large subunit or those from the major surface glycoprotein gene family. Targeting of the internal transcribed spacer (ITS) sequences is used

Primary infection

Evidence for widespread and early acquisition of primary Pneumocystis infection has long been appreciated from serology-based studies [1]. This was recently reconfirmed, and it was further shown that seroconversion rates increase with age [6, 7]. In the first study, a prospective cohort of healthy infants had antibody titers drawn every two months. The percentage of antibody-positive infants increased with age (85% seroconverting at 20 months of age) [6]. A second cross-sectional study showed

Carriage in HIV-positive individuals

Human immunodeficiency virus (HIV)-positive individuals represent the most studied population of Pneumocystis carriers, although estimates of the carriage rate vary dramatically between reports from 9–69% [16, 17, 18••]. The initial observations of a carrier state were obtained when PCR-based assays were evaluated for the diagnosis of PcP in HIV-positive patients. As there was an absence of a fulminant infection, but the presence of P. jirovecii was shown by PCR-based analyses, multiple

Carriage in non-HIV-positive individuals

The high prevalence of Pneumocystis carriage in the immunocompetent rat model has long been recognized [20]. In a similar manner, carriage in humans has now been linked to diverse subpopulations. Many non-HIV-positive people that have immunosuppression, such as organ transplant recipients or those with connective tissue diseases, are at risk of PcP [21]. Likewise, these individuals fall into target populations that have a theoretical risk of Pneumocystis carriage. More subtle changes in immune

Transmission

The increased recognition of Pneumocystis carriers has led to investigation into their role in disease transmission (Figure 1). Animal models of infection have helped to elucidate the route of airborne transmission [30, 31]. Likewise, strain-typing methods have shown that clusters of PcP have originated from a common source [32•, 33]. In the search for a nosocomial transmission source, it has been shown that some asymptomatic healthcare workers are Pneumocystis carriers. 24% of health-care

Conclusions

Although still limited by the lack of a culture method, research into the natural history of Pneumocystis has advanced owing to the expansion of molecular-based techniques. Previous serological data that indicated an almost universal exposure to this fungi has been bolstered by documentation of Pneumocystis DNA in people without illness or with less severe disease than in a classical PcP setting. Likewise, groups at risk for carriage provide a species-specific reservoir of infection, which

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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