March 2000
SANTIAGO, Chile - Researchers have found Pneumocystis carinii in the lungs of a large proportion of infants who died of sudden infant death syndrome (SIDS), but whether there is a causal link is unknown.
 (Figure 1) |
 (Figure 2) |
| Pneumocystis carinii
clusters as found in the lungs of infants diagnosed with sudden infant
death syndrome: (1) Grocott-Gomori methenamine-silver nitrate stain. (2)
Immunohistochemical stain with monoclonal antibody 3F6. (Dako Diagnostics,
Carpinteria, CA) Photos courtesy of Sergio Vargas |
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This is an unusual finding because the organism has been found almost entirely in severely immunocompromised patients, such as those with AIDS. Researchers looked at autopsy lung-tissue specimens of 534 children without AIDS or cancer. They found P. carinii in 25% of infants with a post-autopsy diagnosis of SIDS, compared with 2.9% of children who died of multiple conditions at the hospital. SIDS was diagnosed if no recognized premortem disease existed, there were no significant microscopic or macroscopic pathological findings and toxicology studies were negative.
Initial findings prompted researchers to examine an additional 161 children from Chile and the United Kingdom, who died of SIDS. Thirty-five percent of the 134 Chilean infants and 14.8% of the 27 U.K. infants had P. carinii clusters, compared with 2.9% of 342 infants in the control group. The average age of study group infants was 95 days and 88 days in the control group.
A competent child can produce a strong, local immune response that clears pneumocystis before it becomes a large population in the lung, according to Sergio Vargas, MD, assistant professor of pediatrics and clinical microbiology, University of Chile School of Medicine. However, immunosuppressed patients cannot react to P. carinii infection, so it grows to large numbers reaching massive infection.
"The finding in SIDS infants was a total surprise," said Walter Hughes, MD, professor emeritus, department of infectious diseases, St. Jude Children's Research Hospital, Memphis, Tenn. "We know these are not severely immunosuppressed infants and there isn't enough of the organism in the lungs to cause death. Further studies are needed to delineate the real relationship. Because this organism is found in immunocompromised patients, it could be a marker for what might really be causing SIDS, just as it served as a marker for HIV infection."
Hughes said findings indicate there may be a new direction to head in the search for the cause of SIDS. "Why did the infants have pneumocystis in the lungs? There might be something we don't know about the organism that may in some way affect the lung function in infants that would cause SIDS," he noted.
Serological evidence shows that primary infection by P. carinii is among the most common infections occurring early in life - up to 94% of normal immunocompetent children have detectable antibodies to P. carinii by age 30 months to 48 months. Yet studies on whether or not P. carinii causes clinically overt disease in normal children are lacking.
The study patients' age and mild histological pattern suggest study findings correspond to primary P. carinii infection vs. reactive or secondary infection. Primary P. carinii infection was asymptomatic in most SIDS study cases.
The potential pathogenic role of P. carinii in SIDS cases is unclear. A possible explanation is the reduction in levels of pulmonary surfactant. Patients with P. carinii pneumonia have decreased pulmonary surfactant levels directly related to P. carinii growth occurring at early stages of infection where few pneumocystis organisms can be seen. The level is comparable with the low pneumocystis load found in SIDS babies. The load in SIDS cases was mild and the clusters were hard to find histologically, according to researchers.
Findings suggest P. carinii may play a role, alone or as an accompanying pathogen, in the decreased level of pulmonary surfactant documented in SIDS cases. In other studies, infants with a post-autopsy diagnosis of SIDS consistently showed decreased levels of surfactant. It was previously hypothesized that a decrease in the surfactant level may be a mechanism triggering SIDS when it occurs at a critical stage of lung development.
For more information:
- Hoffman A, Lawrence M, Ognibene F, et al. Reduction of pulmonary surfactant in patients with human immunodeficiency virus infection and Pneumocystis carinii pneumonia. Chest. 992;102:1730-36.
- James D, et al. Surfactant abnormality and the sudden infant death syndrome - a primary or secondary phenomenon? Arch Dis Child.1990;65:774-78.
- Vargas S, et al. Limited persistence and subsequent elimination of Pneumocystis carinii from the lungs after P. carinii pneumonia. J Infect Dis.1995;172:506-10.
- Vargas S, Ponce C, Hughes W, et. al. Association of primary Pneumocystis carinii infection and sudden infant death syndrome. Clin Infect Dis 1999;29:1489-93.
- Beers M, Atochina E, Preston A, et al. Inhibition of lung surfactant protein B expression during Pneumocystis carinii pneumonia in mice. J Lab Clin Med. 999;133:423-33.
- Wright T, Gigliotti F, Finkelstein J, et al. Immune-mediated inflammation directly impairs pulmonary function, contributing to the pathogenesis of Pneumocystis cariniipneumonia. J Clin Invest 1999;104:1307-17.
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