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Letter
Pregnancy and Asymptomatic
Carriage of Pneumocystis jiroveci
Sergio L. Vargas,* Carolina Angelica Ponce,* Catherine Andrea Sanchez,*
Ana Victoria Ulloa,* Rebeca Bustamante,* and Guido Juarez†
*University of Chile School of Medicine, Santiago, Chile; and †University
of Chile Hospital, Santiago, Chile
Suggested citation for this article: Vargas SL, Ponce
CA, Sanchez CA, Ulloa AV, Bustamante R, Juarez G. Pregnancy and asymptomatic
carriage of Pneumocystis jiroveci. Emerg Infect Dis [serial online]
2003 May [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no5/02-0660.htm
To the Editor: Severe immunosuppression is the leading determinant
host factor for Pneumocystis pneumonia (PCP) (1).
However, PCP is not restricted to those who are severely immunocompromised.
Molecular techniques based on the amplification of specific regions of
P. jiroveci (human-derived Pneumocystis) DNA by using polymerase
chain reaction (PCR) in noninvasive human samples suggest that the infection
is common in other segments of the population that are immunocompetent
or display a lesser degree of immune compromise (2,3).
A mild or asymptomatic form of P. jiroveci infection, or a carrier
state, likely develops in these persons, who may play a role in the circulation
of P. jiroveci in the community while serving as silent reservoirs
for transmission to susceptible persons. This description fits infants
who acquire the primary Pneumocystis infection very early in life,
patients with chronic respiratory disorders, elderly adults, and other
groups (2,3). Extensive searches have been unsuccessful
in detecting carriage of P. jiroveci DNA in noninvasive samples
(i.e., nasal and throat swabs, saliva) from immunocompetent healthy adults
(4).
Evidence suggests that latency of P. jiroveci is time-limited
and that PCP is more likely an actively acquired infection (1).
Characterization of potentially infectious reservoirs might lead to new
intervention strategies to prevent transmission. Furthermore, the detection
of P. jiroveci strains with mutations at the dihydropteroate synthase
locus, which in other pathogens confer resistance to trimethoprim-sulfamethoxazole,
suggests that resistance to this primary therapy of PCP may be emerging
(1). New strategies for P. jiroveci prophylaxis
may soon be needed.
Evidence suggests that normal pregnancy may be accompanied by changes
in the immune response that may in part account for the successful growth
and delivery of the “fetus hemi-allograft.” A subtle shift from the response
of Th1 (cellular immunity) CD4+ lymphocytes to a proportional increase
in the Th2 (humoral immunity) CD4+ response can be detected (5).
These responses have not been clearly explained but would most likely
occur because of shifts in the production of cytokines, impairing defense
against certain infections. Pregnancy’s important hormonal changes (e.g.,
increases in the secretion of human chorionic gonadotropin, progesterone,
estrogen, corticosteroids,  -fetoprotein,
prolactin, and -globulin)
may also contribute to decreased resistance. While overt immune deficiency
is difficult to detect, an increase in some viral infections has been
documented, which may indicate a gentle form of depressed immune response
(6). In addition, this physiologic compensation generates
an increase in illness and death from other infections that require a
protective Th1 response as, for example, tuberculosis, malaria, American
trypanosomiasis, leishmaniasis, toxoplasmosis, lysteriosis, and pneumocystosis.
Reports indicate that illness in HIV-infected women with PCP is greater
when the women are pregnant (7). However, no data show
that pregnant women may be asymptomatic carriers of P. jiroveci.
A prospective, pilot study of 33 third-trimester, pregnant, asymptomatic
healthy women and 28 healthy women within 15 days of a menstrual period
(controls) was conducted. Participants were followed at an outpatient
clinic in Santiago during January through March 2002. Ages were 14–39
years (median 26 years) for pregnant women and 17–45 years (median 28
years) for controls. Previous pregnancies ranged from 0 (n=10) to 4 (median
1) for pregnant women and from 0 (n=9) to 3 (median 1) for controls. P.
jiroveci was detected in deep nasal swab samples in a nested-PCR procedure
by using oligonucleotide primers pAZ102E and pAZ102H. (These primers were
designed for the gene encoding the mitochondrial large subunit rRNA of
rat-derived Pneumocystis [P. carinii] that amplifies all
forms of Pneumocystis and internal primers pAZ102X and pAZ102Y,
specific for P. jiroveci.) DNA extraction was performed with a
commercial kit (QIAamp DNA mini kit; Qiagen Inc., Valencia, CA). Positive,
negative, and internal control primers, directed to the human globin gene
to detect sample inhibition and verify successful extraction, were used
during the DNA amplification procedure. Samples were processed under a
laminar flow hood to prevent contamination, and PCR assays were repeated
twice. The Ethics Committee of the University of Chile School of Medicine
approved the study.
Five (15.5%) of the 33 pregnant women had P. jiroveci DNA in their
nasal swab samples versus none (0%) of the 28 nonpregnant controls (p=0.04
by 1-sided Fisher exact test). Immunologic parameters were not tested.
The P. jiroveci–positive women were all multiparous with 1 (n=2),
2 (n=2), or 3 (n=1) previous pregnancies.
These results suggest that pregnancy is a host factor that favors asymptomatic
nasal carriage of P. jirovec. However, PCR detection of P. jiroveci
DNA in the nares of pregnant women does not necessarily indicate either
a mild active pulmonary infection or viable or transmissible organisms.
In animal models, detection of P. carinii DNA in nasal and oral
samples is a good indicator that Pneumocystis is in the lungs (8).
These results also support the hypothesis that pregnant women who nasally
carry P. jiroveci may play a role as contagious sources for susceptible
persons, especially their immunologically naive newborn infants. This
hypothesis warrants further study. Mother-to-infant transmission may explain
the accumulating evidence that the primary infection is widely acquired
very early in life (9). Recent animal model studies have
documented the early acquisition of P. carinii (within 1 to 2 h
after birth) in neonatal rats, likely transmitted by the dams (10).
Evidence of mother-offspring transmission would be clinically relevant
for infants born to HIV-infected mothers, who currently rely on empiric
anti-Pneumocystis chemotherapy started at 1 month of age as their
only prophylactic option.
Acknowledgments
We thank Henry N. Claman for critically reviewing the
manuscript in aspects related to human pregnancy.
This study was supported by grant PG 51153-26 from the
Elizabeth Glaser Pediatric AIDS Foundation; by Fondo Nacional de Desarrollo
Científico y Tecnológico (FONDECYT research grant 1011059), Santiago,
Chile; and by a 2002 research award from the Hospital Clínico de la
Universidad de Chile.
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