To the Editor: Severe immuno-suppression 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, [alpha]-fetoprotein, prolactin, and [alpha]-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 sub-unit 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=l) 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 Cientifico y Tecnol6gico (FONDECYT research grant 1011059), Santiago, Chile; and by a 2002 research award from the Hospital Clinico de la Universidad de Chile.
References
(1.) Wakefield AE. Pneumocystis carinii. Br Med Bull 2002;61:175-88.
(2.) Contini C, Villa MP, Romani R, Merolla R, Delia S, Ronchetti R. Detection of Pneumocystis carinii among children with chronic respiratory disorders in the absence of HIV infection and immunodeficiency. J Med Microbiol 1998;47:329-33.
(3.) Sing A, Geiger AM, Hogardt M, Heesemann J. Pneumocystis carinii carriage among cystic fibrosis patients, as detected by nested PCR. J Clin Microbiol 2001;39:2717-8.
(4.) Oz HS, Hughes WT. Search for Pneumocystis carinii DNA in upper and lower respiratory tract of humans. Diagn Microbiol Infect Dis 2000;37:161-4.
(5.) Wegmann TG, Lin H, Guilbert L, Mosmann TR. Biderectional cytokine interactions in the maternal-fetal relationship:is successful pregnancy a TH-2 phenomenon? Immunol Today 1993;14:353-6.
(6.) Claman HN. The immunology of human pregnancy. Totowa (NJ): Humana Press; 1993.
(7.) Ahmad H, Mehta N, Manikal VM, Lamoste T J, Chapnick EK, Lutwick LI, et al. Pneumocystis carinii pneumonia in pregnancy. Chest 2001; 120:666-71.
(8.) Oz HS, Hughes WT. DNA amplification of nasopharyngeal aspirates in rats: a procedure to detect Pneumocystis carinii. Microb Pathog 1999;27:119-21.
(9.) Miller RF, Ambrose HE, Novelli V, Wakefield AE. Probable mother to infant transmission of Pneumocystis carinii f. sp. hominis infection. J Clin Microbiol 2002;40:1555-7.
(10.) Icenhour CR, Rebholz S, Collins MS, Cushion MT. Evidence for early acquisition of Pneumocystis carinii in neonatal rats using PCR and oral swabs. Eukaryotic Cell 2002; 1:414-9.
Address for correspondence: Sergio L. Vargas, Respiratory Infections Laboratory, Program in Microbiology and Mycology, Biomedical Sciences Institute, University of Chile School of Medicine, Independencia 1027, Santiago, Chile; fax: +56-2-732 5160; email: svargas@terra.cl
Sergio L. Vargas, * Carolina Angelica Ponce, * Catherine Andrea Sanchez, * Ana Victoria Ulloa, * Rebeca Bustamante, * and Guido Juarez ([dagger])
* University of Chile School of Medicine, Santiago, Chile; and ([dagger]) University of Chile Hospital, Santiago, Chile
COPYRIGHT 2003 U.S. National Center for Infectious Diseases
COPYRIGHT 2003 Gale Group
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