of AIDS in the 1980s Pneumocystis was only found
infrequently as a cause of pneumonitis, called Pneu-
mocystis carinii pneumonia (PCP). It was found
first in malnourished children and then in patients
undergoing immunosuppressive therapies. Now PCP
has become one of the commonest causes of death of
AIDS patients, and there is a direct correlation between
the risk of developing PCP and a low number of circu-
lating CD4+T lymphocytes. A cell count of 200 or less
per microliter of blood is the critical lower limit.
It is notable that a very high proportion of children
in Europe and the USA show a positive serum test for
Pneumocystisantigens by the age of 4 years, indicating
exposure to the fungus. This is probably also true
for most other countries. However, Pneumocystisthen
seems to disappear from the lungs and only returns
as people age, or in response to immunosuppression.
Thus Pneumocystisinfection is strongly age-linked, and
re-infections later in life probably result from wide-
spread and constant re-exposure to the fungus.
Soon after Pneumocystis cariniihad been formally
transferred to the fungal kingdom, DNA sequence
analysis showed that strains obtained from different
animal hosts were very diverse and each was specific
for the individual host species. Using the polymerase
chain reaction, primers were developed to amplify
DNA from all known species of Pneumocystis, and each
of these was found to be distinct and host-specific, with
no evidence of cross-infection from one host species
to another. Confirmation of this in several studies has
led to the proposal that all the host-specific forms of
Pneumocystisshould be regarded as separate species.
Thus, the human-host-specific fungus has been named
P. jiroveci, and the original name P. cariniihas been
retained for one of the two known Pneumocystis
species found in rats. Pneumocystisorganisms obtained
from rats, mice, ferrets, pigs, and monkeys all show host-
species specificity and new names for these are likely
to be proposed. Consistent with the co-evolution of par-
asites with their hosts, the Pneumocystisspecies from
humans are most similar to (although distinct from)
those of other primates.Modes of transmission, pathology, and
the life cycle of PneumocystisPneumocystiscannot be maintained for long in labor-
atory culture, so it seems to be essentially an obligate
parasite. Small amounts of DNA of P. jirovecihave
been detected in environmental samples, including
samples of airborne spores and pond water, but the most
likely source of infection is either the activation of
a pre-existing latent infection or re-infection from
inhaled spores. The fungus escapes the defenses of the
upper respiratory tract, and establishes infections in thealveoli, apparently by binding to the type 1 epithelial
cells.
The life cycle of Pneumocystisis complicated, and still
incompletely understood. Asexual trophic (feeding)
forms proliferate by mitosis in the lungs. There is also
a sexual stage in which haploid cells conjugate to pro-
duce a diploid pre-cyst. This undergoes meiosis, followed
by mitosis, to produce eight haploid nuclei in the
“late phase cyst.” Mature cysts are variable in shape but
often have a saucer-like appearance (Fig. 16.10). They
are thought to rupture, releasing haploid vegetative cells.
In immunocompromised people the Pneumocystis
cells proliferate and can result in tiers of cells up to four
layers thick in the alveolar lumen, creating oxygen
deficiency. A foamy alveolar exudate is produced,
and in advanced stages of disease the fungus can be
detected in all major organs of the body, especially the
lymph nodes, bone marrow, liver, and spleen.
DNA sequence polymorphisms have often been
found in isolates of the human pathogen P. jiroveci,
indicating that many strains exist within this species.
For example, polymorphisms have been found in
the mitochondrial 18S ribosomal RNA gene, the
mitochondrial small subunit rRNA gene, the internal
transcribed spacer (ITS) regions of the nuclear rRNA
gene, and the dihydropteroate synthase (DHPS) gene.
These polymorphisms provide the basis for investig-
ating the epidemiology of Pneumocystisinfections
in humans. Comparisons of strains collectedbefore
(1968 –1981) and after (1982 to present) the beginning
of the AIDS pandemic indicate that there has been no
substantial change in the Pneumocystis population that
could account for the massive increase in AIDS-related
pneumonia. DNA sequence polymorphisms have also
been used to investigate whether PCP (pneumonia)
exists in a long-term latent form in humans or is re-336 CHAPTER 16
Fig. 16.10Saucer-shaped cysts of Pneumocystis jiroveci(Re-
produced with permission from Centers for Disease Control
and Prevention, Image Library; http://www.dpd.cdc.gov/
dpdx/HTML/ImageLibrary/Pneumocystis_il.htm)FB4eC16 04/20/2005 02:53PM Page 336