Emerging Infectious Diseases Hemorrhage and Shock Associated with Invasive Pneumococcal Infection in Healthy Infants and Children -- New Mexico, 1993-1994

From December 1993 through May 1994, four previously healthy children (including two infants) in New Mexico developed a severe illness characterized by septic shock and hemorrhage into the skin or internal organs. An investigation subsequently implicated Streptococcus pneumoniae as the cause of illness. The two infants attended the same child care center (CCC) and died 6 weeks apart. This report describes the syndrome, an investigation of potential transmission in the CCC, and prevention measures. Case Investigations

On December 10, 1993, the New Mexico Department of Health (NMDH) received a report of a previously healthy 4-month-old girl (patient 1) who died from septic shock with petechiae and hemorrhage into the adrenal glands, heart, and diaphragm. Blood and tissue cultures were negative. However, because her clinical presentation suggested meningococcemia, a prophylactic regimen of rifampin was prescribed for infants, toddlers, and staff at the CCC she attended. On February 9, 1994, a 7-month-old infant (patient 2) who attended the same CCC died from septic shock, purpura, and Waterhouse-Friderichsen syndrome. Gram-positive cocci were detected on a smear of the patient's blood buffy coat, and a latex agglutination test on cerebrospinal fluid (CSF) indicated infection with S. pneumoniae as the cause of death; pneumococcal infection was confirmed by polymerase chain reaction (PCR), using primers for the pneumococcal autolysin gene on autopsy tissue, and by counterimmunoelectrophoresis (CIE) of CSF (serogroup 19). Analysis of autopsy tissue from patient 1, using the same PCR assay, suggested that she also had died from pneumococcal infection.

On February 17 and May 13, 1994, NMDH received reports of two other previously healthy children in whom septic shock and purpura fulminans had been diagnosed but who resided in different communities and who did not attend the CCC. Both children (aged 22 months and 4 years) were critically ill but fully recovered. Routine cultures were negative for both patients, but S. pneumoniae (serogroups 14 and 12, respectively) was detected by CIE of CSF from each child. CCC Investigation

After determining the specific cause of death for the two infants, NMDH evaluated potential transmission of pneumococcal disease in the CCC. At the time of the investigation (February 9- March 25), 75 children aged 6 weeks-10 years were enrolled in the CCC, and 17 persons were employees there. CCC attendees were divided into classrooms by age: the infant group (age less than 1 year) had infrequent contact with the toddler group (age 1-2 years) and no contact with the older children. Staff rotated between the classrooms. The CCC staff routinely adhered to infection-control procedures that were consistent with state and federal guidelines, including handwashing after diaper changes and exclusion of infants and children with potentially infectious illnesses (1).

To characterize the number and type of illnesses occurring among attendees aged less than or equal to 2 years during the 2-week periods preceding the two infants' deaths, NMDH conducted a self-administered survey of CCC staff and parents of CCC attendees. Parents were asked if their children had symptoms including cough, fever, and conjunctivitis or if a physician had told them their child had otitis media, pneumonia, or sinusitis -- illnesses suggestive of pneumococcal infection. Six of the nine members of the infant group (excluding patients 1 and 2) and four of eight in the toddler group had had illnesses suggestive of pneumococcal infection during November 26-December 10, 1993. Otitis media was diagnosed by a physician for the six ill infants and three of the four ill toddlers; one of the ill toddlers had had purulent conjunctivitis. During January 25-February 8, 1994, illnesses suggestive of pneumococcal infection were diagnosed in five of the nine infants (four with otitis media and one with otitis media and pneumonia) and two of the eight toddlers (one with otitis media and one with otitis media and purulent conjunctivitis).

To assess the prevalence of pneumococcal carriage, on February 11, nasopharyngeal samples were obtained from CCC staff and from children in the infant and toddler groups. Of the 38 persons from whom swabs were obtained, pneumococci were isolated from six children and two staff (serogroup 19 in two infants and one toddler).

To prevent additional cases among children and staff at the CCC, NMDH and CDC, in consultation with University of New Mexico clinicians, recommended pneumococcal polysaccharide vaccine for all children aged greater than or equal to 2 years and for all staff. Because the vaccine is poorly immunogenic in children aged less than 2 years, health officials recommended those children receive one dose of benzathene penicillin administered intramuscularly with a repeat dose 1 month later. Reported by: L Nims, MS, K Hatch, M Gallaher, MD, R Voorhees, MD, M Tanuz, I Vold, MPH, M Goldstein, MD, C Powers, J Knott, N Kalishman, MD, G Simpson, MD, CM Sewell, DrPH, State Epidemiologist, New Mexico Dept of Health; A Paul, MD, L Shandler, MD, Santa Fe, New Mexico; KB Nolte, MD, New Mexico Office of the Medical Investigator; G Overturf, MD, Univ of New Mexico Hospital, Albuquerque. J Groover, D Musher, MD, Veteran's Administration Medical Center, Houston. Childhood and Respiratory Diseases Br, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: S. pneumoniae is the most common cause of invasive bacterial disease in the United States (2). The findings in New Mexico indicate that systemic pneumococcal infection in previously healthy children may be complicated by the rapid onset of septic shock accompanied by hemorrhage into the skin or other organs. Overwhelming sepsis with hemorrhagic complications has been well documented in persons who are asplenic and in adults with underlying medical conditions (3,4). However, reports of hemorrhage and shock associated with pneumococcal septicemia in previously healthy children have been limited and have included cases in a previously healthy 13-month-old who developed fatal Waterhouse-Friderichsen syndrome (5); two children with purpura fulminans (6); and two children with pneumococcal septicemia, shock, and hemorrhagic complications (7).

Because CSF, blood, and tissue cultures were negative, determining the etiology of the four cases in New Mexico required use of alternative diagnostic methods. Latex agglutination testing is performed on CSF specimens of some patients with suspected bacterial meningitis. CIE, a technique not commonly used, is highly specific for most pneumococcal serogroups when used on CSF specimens, but its sensitivity may be lower than that of other methods (8). The validity of PCR using primers for the pneumococcal autolysin gene on autopsy tissue has not been evaluated (9).

Although the most common pneumococcal diseases in persons in CCCs include otitis media and sinusitis, transmission of invasive pneumococcal disease in this setting has been reported previously (10). The report of the two deaths among children who attended the New Mexico CCC underscores the need to improve prevention of pneumococcal disease transmission in CCCs. However, until a vaccine effective in children aged less than 2 years is developed and licensed, substantial morbidity from pneumococcal infections among children in CCCs will probably continue to occur.

The incidence of hemorrhage and shock as a complication of pneumococcal infection in healthy children is unknown. Identification of S. pneumoniae as the etiology of infection in a child with this presentation is difficult when cultures are negative and other diagnostic tests are not performed. CDC recommends the following case definition to facilitate further study and reporting of this illness: septic shock, hemorrhage into the skin (petechiae or purpura) or Waterhouse-Friderichsen syndrome, and evidence of pneumococcal infection in an otherwise healthy person. Evidence of pneumococcal infection may include isolation of pneumococci from sterile body fluids or detection of pneumococci by nonculture methods. If CSF or autopsy tissues are available and routine diagnostic tests are negative, CDC can assist with detection or characterization of pneumococci. Physicians and other health-care providers are encouraged to report patients with this clinical presentation to CDC through their state health departments.

References

1. American Public Health Association/American Academy of Pediatrics. Caring for our children -- national health and safety performance standards: guidelines for out-of-home child care programs. Washington, DC: American Public Health Association/American Academy of Pediatrics, 1992.

2. Wenger JD, Hightower AW, Facklam RR, Gaventa S, Broome CV, and the Bacterial Meningitis Study Group. Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. J Infect Dis 1990;162:1316-23.

3. Hautekeete ML, Berneman ZN, Bieger R, et al. Purpura fulminans in pneumococcal sepsis. Arch Intern Med 1986;146:497-9.

4. Johansen K, Hansen ST. Symmetrical peripheral gangrene (purpura fulminans) complicating pneumococcal sepsis. Am J Surg 1993;165:642-5.

5. Ryan CA, Wenman W, Henningsen C, Tse S. Fatal childhood pneumococcal Waterhouse-Friderichsen syndrome. Pediatr Infect Dis J 1993;12:250-1.

6. Cohen JR, Lackner R, Keller A, Douglas B. The surgical implications of purpura fulminans. Ann Vasc Surg 1990;4:276-9.

7. Floret D, Andre S. Fulminating pneumococcal septicemia in children. Pediatrie 1985;40:475-80.

8. Ballard TL, Roe MH, Wheeler RC, Todd JK, Glode MP. Comparison of three latex agglutination kits and counterimmunoelectrophoresis for the detection of bacterial antigens in a pediatric population. Pediatr Infect Dis J 1987;6:630-4.

9. Rudolph KM, Parkinson AJ, Black CM, Mayer LW. Evaluation of polymerase chain reaction for diagnosis of pneumococcal pneumonia. J Clin Microbiol 1993;31:2661-6.

10. Cherian T, Steinhoff MC, Harrison LH, Rohn D, McDougal LK, Dick J. A cluster of invasive pneumococcal disease in young children in child care. JAMA 1994;271:695-7.

    
    

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