Correspondence

Pneumocystis in Infants and Children

N Engl J Med 1995; 333:320-321August 3, 1995

Article

To the Editor:

Each of two important reports on Pneumocystis carinii in the March 23 issue1,2 lacks convincing proof of diagnosis.

The letter by Mortier et al.1 describes maternal–fetal transmission of P. carinii associated with HIV infection. The case is based on the finding of up to 20 P. carinii cysts in each of five intraalveolar macrophages in the lungs of a dead fetus delivered of a mother in whom P. carinii cysts had been detected within the previous three weeks. Unfortunately, the color photomicrograph used to demonstrate the presence of P. carinii cysts does not show organisms recognizable as P. carinii or a discernible macrophage. The Gomori stain used does not stain macrophages, and nonbudding yeasts may resemble P. carinii cysts. Staining with Giemsa stain and fluorescein-labeled monoclonal antibodies, both of which are in general use, would have provided more definitive identification.

The article by Simonds et al.2 provides useful information on P. carinii pneumonia in HIV-infected infants. The study reviews records of 300 infants and children given the diagnosis of P. carinii pneumonia. Unfortunately, P. carinii was not documented as the cause of the pneumonia in 81 (27 percent) of the cases. No criteria were given for the presumptive diagnosis of the unproved cases. Thus, conceivably up to 27 percent of the infants and children could have had pneumonia due to causes other than P. carinii. Interestingly, the authors point out that as many as 23 percent of the children in this study had P. carinii pneumonia while receiving prophylaxis against it. This breakthrough rate is considerably higher than that reported in documented cases, suggesting that some of the cases were not due to P. carinii. A subgroup analysis of proved cases would have strengthened the study.

Walter T. Hughes, M.D.
St. Jude Children's Research Hospital, Memphis, TN 38105

2 References

1. 1

   Mortier E, Pouchot J, Bossi P, Molinie V. Maternal-fetal transmission of Pneumocystis carinii in human immunodeficiency virus infection. N Engl J Med 1995;332:825-825
   Full Text | Web of Science | Medline

2. 2

   Simonds RJ, Lindegren ML, Thomas P, et al. Prophylaxis against Pneumocystis carinii pneumonia among children with perinatally acquired human immunodeficiency virus infection in the United States. N Engl J Med 1995;332:786-790
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: In our letter on maternal–fetal transmission of P. carinii in cases of infection with the human immunodeficiency virus, identification of P. carinii cysts in maternal bronchoalveolar lavage relied on both Gomori–methenamine silver and Giemsa stains, as well as fluorescein-labeled monoclonal-antibody stain. We agree with Dr. Hughes that P. carinii cysts were not strictly recognizable in the photomicrograph of the fetal lung. Identification of P. carinii cysts in the fetal-lung sections originally relied on both Gomori–methenamine silver and Giemsa stains. The cysts were located within cells morphologically identified as macrophages. However, no monoclonal-antibody stain specific for macrophages was used. After reading Dr. Hughes's letter, we processed additional paraffin-embedded fetal-lung sections with fluorescein-labeled monoclonal-antibody stain and unfortunately obtained negative results. However, this technique is usually used with frozen sections or imprints, which were not available because all samples were fixed with Bouin's fluid and embedded in paraffin before examination. Therefore, we cannot add further data to confirm the pathologic evidence of vertical transmission of P. carinii that we presented.

Emmanuel Mortier, M.D.
Jacques Pouchot, M.D.
Vincent Molinié, M.D.
Hôpital Louis Mourier, 92701 Colombes, France

Author/Editor Response

As Dr. Hughes suggests, some of the children in our study who were given the presumptive diagnosis of P. carinii pneumonia may have actually had pneumonia due to other causes. Our study was based largely on cases identified through surveillance by state and local health departments for AIDS. Because patients are not always able to undergo the procedures necessary to diagnose P. carinii pneumonia definitively, it may be diagnosed in some cases on the basis of clinical and radiologic findings. For the purpose of surveillance, such are considered presumptively diagnosed cases of P. carinii pneumonia. The suggested criteria for a presumptive diagnosis of the disease are a history of dyspnea or recent nonproductive cough, radiographic evidence of diffuse bilateral interstitial infiltrate, hypoxemia, and no evidence of bacterial pneumonia.1

The proportion of children in our study who were reported to be receiving prophylaxis when P. carinii pneumonia was diagnosed was 24 percent among the 74 children with presumptively diagnosed disease and 23 percent among the 219 children with definitively diagnosed disease. This proportion, however, should not be considered to represent a rate of “breakthrough” cases for two reasons. First, our study design relied on medical-record review and did not allow us to assess adherence to the prophylaxis regimen; it is likely that some of the children reported to be receiving prophylaxis were not actually taking the medication. Second, to calculate such a rate, the incidence of P. carinii pneumonia must be calculated among a group of HIV-infected children receiving prophylaxis. Our study did not include such a group, but rather only children in whom P. carinii pneumonia had developed.

As Dr. Hughes indicates, the rate of P. carinii pneumonia among children receiving prophylaxis is low. Among 70 HIV-infected children who were monitored prospectively through the first 18 months of life as part of the New York City Perinatal HIV Transmission Collaborative Study and who received trimethoprim–sulfamethoxazole prophylaxis, P. carinii pneumonia developed in only 3 (4 percent).2 These data and those from other populations3 indicate that trimethoprim–sulfamethoxazole is highly effective in preventing P. carinii pneumonia. Our challenge now is to identify children at risk for the disease in time to offer this effective prophylaxis as recommended.4

R.J. Simonds, M.D.
Mary Lou Lindegren, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333

Polly Thomas, M.D.
New York City Department of Health, New York, NY 10013

4 References

1. 1

   Revision of the CDC surveillance case definition for acquired immunodeficiency syndromeMMWR Morb Mortal Wkly Rep 1987;36:Suppl 1S:1S-15s
   

2. 2

   Thea DM, Lambert G, Weedon J, et al. Benefit of primary prophylaxis prior to 18 months of age in reducing the incidence of Pneumocystis carinii pneumonia and early death in a cohort of 112 HIV-infected infants. Pediatrics (in press).
   

3. 3

   Hughes WT, Kuhn S, Chaudhary S, et al. Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 1977;297:1419-1426
   Full Text | Web of Science | Medline

4. 4

   1995 Revised guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virusMMWR Morb Mortal Wkly Rep 1995;44:1-11
   Medline

Citing Articles (2)

Citing Articles

1. 1

   Catherine A. Sanchez, Catherine A. Sanchez, Magali Chabé, El Moukhtar Aliouat, Isabelle Durand-Joly, Nausicaa Gantois, Valérie Conseil, Claudia López, Thérése Duriez, Eduardo Dei-Cas, Sergio L. Vargas. (2007) Exploring transplacental transmission of Pneumocystis oryctolagi in first-time pregnant and multiparous rabbit does. Medical Mycology 45:8, 701-707
   CrossRef

2. 2

   Melanie T. Cushion. (2004) Pneumocystis: unraveling the cloak of obscurity. Trends in Microbiology 12:5, 243-249
   CrossRef