Linking Pneumocystis epidemiology, transmission, and virulence.

Since the beginning of the 1980s, outbreaks and clusters of Pneumocystis pneumonia (PCP) in immunocompromised populations have been reported with some regularity. Interhuman transmission of Pneumocystis jirovecii was already then suspected by the attending clinicians [1]. Long before this time, shortly after World War II, PCP was reported to occur clustered in institutionalized populations of malnourished or debilitated infants [2]. The advent of polymerase chain reaction enabled the development and application of genotyping methods for P. jirovecii in recent PCP outbreaks. A single or predominant P. jirovecii genotype was found in most of these epidemics, and the results were interpreted as being compatible with either interhuman transmission or a common environmental source [3]. Furthermore, postmortem studies as well as screening of respiratory samples showed that P. jirovecii can be detected in the lungs and airways of both healthy and immunocompromised individuals not having clinically manifest PCP [4, 5]. This phenomenon, characterized as colonization with P. jirovecii, is most likely a common condition. Distinct species of Pneumocystis are strictly linked to a specific mammalian host, and comparative sequencing studies revealed that coevolution of Pneumocystis species and their hosts has taken place over the past millions of years [6]. Together these discoveries have led to the prevailing insight that the human population is the only reservoir for P. jirovecii. Notwithstanding the recent advances, the population dynamics of colonization as well as the extent of genetic and pathogenic diversity within the P. jirovecii species are still largely unknown. Against this background, a study by Sassi et al, published in this issue of Clinical Infectious Diseases [7], explored the genetic similarity (or difference) between P. jirovecii isolates from 3 separately described PCP outbreaks among renal transplant recipients by using a new method based on restriction fragment length polymorphism genotyping. In particular, the study was designed to investigate whether a distinct strain with increased virulence might explain these sudden elevations in PCP incidence. From all 3 outbreaks, P. jirovecii DNA from a subset of involved cases was available and analyzed (Munchen, 13 of 16 cases; Zurich, 7 of 19; and Nagoya, 9 of 33). The confirmation that P. jirovecii isolates were genetically identical within outbreaks makes it unlikely that a longstanding prior P. jirovecii colonization simultaneously transitioned into clinically manifest pneumonia in multiple patients, induced by increased immune suppression. Exactly how then do PCP outbreaks originate and develop? The occurrence of PCP outbreaks is a rare event even in immunocompromised populations at risk, that is, those not receiving prophylaxis. Thus, the presence of a set of specific conditions seems required to temporarily raise the reproduction number above 1. Despite the results reported by Sassi et al [7], there are still multiple possible explanations for the genesis of a PCP outbreak in a susceptible population. A first hypothesis is that increased infectious pressure, with a subsequent PCP outbreak, originates from peak rates of colonization in the general population that includes the susceptible individuals. If colonization within this population is dominated by a single genotype, this would clarify the genotyping results of the current study and other PCP outbreak studies. In the study by Sassi et al [7], it would particularly explain how the 2 apparently separately evolving European outbreaks were caused by the same genotype. Although 300 km apart, the different locations could be part of the same geographic region with regard to colonization. Whether this hypothesis is (See the Major Article by Sassi et al, on pages 1437–44.)