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Near-universal prevalence of Pneumocystis and associated increase in mucus in the lungs of infants with sudden unexpected death.

Vargas SL, Ponce CA, Gallo M, Pérez F, Astorga JF, Bustamante R, Chabé M, Durand-Joly I, Iturra P, Miller RF, Aliouat el M, Dei-Cas E - Clin. Infect. Dis. (2012)

Bottom Line: The infection was commonest at 3-4 months with 40 of 41 (97.6%) infants of that age testing positive.MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013).A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Programa de Microbiología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago, Chile. svargas@med.uchile.cl

ABSTRACT

Background: Pneumocystis without obvious accompanying pathology is occasionally reported in autopsied infant lungs. Its prevalence and significance are unknown. Interestingly, this mild infection induces a strong activation of mucus secretion-related genes in young immunocompetent rodents that has not been explored in infants. Excess mucus is induced by multiple airway offenders through nonspecific pathways and would explain a cofactor role of Pneumocystis in respiratory disease. We undertook characterization of the prevalence of Pneumocystis and associated mucus in infant lungs.

Methods: Samples from 128 infants (mean age, 101 days) who died suddenly and unexpectedly in Santiago during 1999-2004 were examined for Pneumocystis using nested polymerase chain reaction (nPCR) amplification of the P. jirovecii mtLSU ribosomal RNA gene and immunofluorescence microscopy (IF). Pneumocystis-negative infants 28 days and older and their age-closest positives were studied for MUC5AC expression and Pneumocystis burden by Western blot and quantitative PCR, respectively.

Results: Pneumocystis DNA was detected by nPCR in 105 of the 128 infants (82.0%) and Pneumocystis organisms were visualized by IF in 99 (94.3%) of the DNA-positive infants. The infection was commonest at 3-4 months with 40 of 41 (97.6%) infants of that age testing positive. MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013). Death was unexplained in 113 (88.3%) infants; Pneumocystis was detected in 95 (84.0%) of them vs 10 of 15 (66.7%) with explained death (P = .28).

Conclusions: A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis.

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Related in: MedlinePlus

Diagnosis of Pneumocystis in infant biopsy specimensrequires sensitive techniques applied to homogenized tissue: Percentage ofPneumocystis detection as relative to nested polymerase chainreaction (n-PCR), of immunofluorescence microscopy (IF), and single-round PCR inhomogenized lung tissue specimens of 36 infants. Results of microscopy readingsusing rapid Giemsa (Diff-Quick) and Gomori-Grocott methenamine silver (GMS) stainsin imprints of cruent-cut-surface lung tissue adjacent to the sections analyzed byn-PCR and IF are also presented. Abbreviations: IF, immunofluorescence microscopy;GMS, Gomori-Grocott methenamine silver; n-PCR, nested polymerase chain reaction;PCR, polymerase chain reaction.
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CIS870F1: Diagnosis of Pneumocystis in infant biopsy specimensrequires sensitive techniques applied to homogenized tissue: Percentage ofPneumocystis detection as relative to nested polymerase chainreaction (n-PCR), of immunofluorescence microscopy (IF), and single-round PCR inhomogenized lung tissue specimens of 36 infants. Results of microscopy readingsusing rapid Giemsa (Diff-Quick) and Gomori-Grocott methenamine silver (GMS) stainsin imprints of cruent-cut-surface lung tissue adjacent to the sections analyzed byn-PCR and IF are also presented. Abbreviations: IF, immunofluorescence microscopy;GMS, Gomori-Grocott methenamine silver; n-PCR, nested polymerase chain reaction;PCR, polymerase chain reaction.

Mentions: Pneumocystis jirovecii DNA was detected by nPCR in the first 36 infantsstudied; 34 (94.4%) of them tested positive by immunofluorescence microscopy, and 2(5.6%) by single PCR in the same homogenized tissue aliquot. Diff-Quick andGomori-Grocott methenamine silver stains detected Pneumocystis trophicforms in 18 (50.0%) and cyst forms in 11 (30.6%), of lung tissue imprints(Figures 1 and 2). Figure 1.


Near-universal prevalence of Pneumocystis and associated increase in mucus in the lungs of infants with sudden unexpected death.

Vargas SL, Ponce CA, Gallo M, Pérez F, Astorga JF, Bustamante R, Chabé M, Durand-Joly I, Iturra P, Miller RF, Aliouat el M, Dei-Cas E - Clin. Infect. Dis. (2012)

Diagnosis of Pneumocystis in infant biopsy specimensrequires sensitive techniques applied to homogenized tissue: Percentage ofPneumocystis detection as relative to nested polymerase chainreaction (n-PCR), of immunofluorescence microscopy (IF), and single-round PCR inhomogenized lung tissue specimens of 36 infants. Results of microscopy readingsusing rapid Giemsa (Diff-Quick) and Gomori-Grocott methenamine silver (GMS) stainsin imprints of cruent-cut-surface lung tissue adjacent to the sections analyzed byn-PCR and IF are also presented. Abbreviations: IF, immunofluorescence microscopy;GMS, Gomori-Grocott methenamine silver; n-PCR, nested polymerase chain reaction;PCR, polymerase chain reaction.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3526255&req=5

CIS870F1: Diagnosis of Pneumocystis in infant biopsy specimensrequires sensitive techniques applied to homogenized tissue: Percentage ofPneumocystis detection as relative to nested polymerase chainreaction (n-PCR), of immunofluorescence microscopy (IF), and single-round PCR inhomogenized lung tissue specimens of 36 infants. Results of microscopy readingsusing rapid Giemsa (Diff-Quick) and Gomori-Grocott methenamine silver (GMS) stainsin imprints of cruent-cut-surface lung tissue adjacent to the sections analyzed byn-PCR and IF are also presented. Abbreviations: IF, immunofluorescence microscopy;GMS, Gomori-Grocott methenamine silver; n-PCR, nested polymerase chain reaction;PCR, polymerase chain reaction.
Mentions: Pneumocystis jirovecii DNA was detected by nPCR in the first 36 infantsstudied; 34 (94.4%) of them tested positive by immunofluorescence microscopy, and 2(5.6%) by single PCR in the same homogenized tissue aliquot. Diff-Quick andGomori-Grocott methenamine silver stains detected Pneumocystis trophicforms in 18 (50.0%) and cyst forms in 11 (30.6%), of lung tissue imprints(Figures 1 and 2). Figure 1.

Bottom Line: The infection was commonest at 3-4 months with 40 of 41 (97.6%) infants of that age testing positive.MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013).A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Programa de Microbiología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago, Chile. svargas@med.uchile.cl

ABSTRACT

Background: Pneumocystis without obvious accompanying pathology is occasionally reported in autopsied infant lungs. Its prevalence and significance are unknown. Interestingly, this mild infection induces a strong activation of mucus secretion-related genes in young immunocompetent rodents that has not been explored in infants. Excess mucus is induced by multiple airway offenders through nonspecific pathways and would explain a cofactor role of Pneumocystis in respiratory disease. We undertook characterization of the prevalence of Pneumocystis and associated mucus in infant lungs.

Methods: Samples from 128 infants (mean age, 101 days) who died suddenly and unexpectedly in Santiago during 1999-2004 were examined for Pneumocystis using nested polymerase chain reaction (nPCR) amplification of the P. jirovecii mtLSU ribosomal RNA gene and immunofluorescence microscopy (IF). Pneumocystis-negative infants 28 days and older and their age-closest positives were studied for MUC5AC expression and Pneumocystis burden by Western blot and quantitative PCR, respectively.

Results: Pneumocystis DNA was detected by nPCR in 105 of the 128 infants (82.0%) and Pneumocystis organisms were visualized by IF in 99 (94.3%) of the DNA-positive infants. The infection was commonest at 3-4 months with 40 of 41 (97.6%) infants of that age testing positive. MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013). Death was unexplained in 113 (88.3%) infants; Pneumocystis was detected in 95 (84.0%) of them vs 10 of 15 (66.7%) with explained death (P = .28).

Conclusions: A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis.

Show MeSH
Related in: MedlinePlus