Correspondence

Group B Streptococcal Disease in Adults

N Engl J Med 1993; 329:1658-1659November 25, 1993

Article

To the Editor:

With regard to the article by Farley et al.1 and the editorial by Wessels and Kasper2 (June 24 issue): The defects in immune defenses in patients with cancer are extremely heterogenous in type and severity and cannot be simplistically characterized as specific defects in host immunity2. A patient with Hodgkin's disease who is taking steroids and who has neutropenia after combination chemotherapy is quite different from a patient with a recent mastectomy for localized breast cancer. If cancer is to be considered a risk factor for an infectious disease, it would be worthwhile to attempt to clarify the nature of the immune defect, particularly when the risk seems to be confined to younger patients only1 -- a group more likely to receive aggressive chemotherapy, radiation, or surgical therapy. Group B streptococcus may be a normal colonizer of the gut3,4. How many patients had risk factors for a breach of mucosal integrity, such as therapy-related mucositis, neutropenia, or gastrointestinal neoplasia? A mortality rate of 21 percent in this hospitalized population, accounting for 67 percent of the deaths in the surveillance group, is worrisome, but how many of these patients had advanced incurable cancer, preexisting irretrievable organ failure, or concomitant gram-negative or resistant enterococcal sepsis? In the case of patients with cancer, group B streptococcus is not a major pathogen. The relative importance of these issues must be clarified before the authors' suggestions for preventive, diagnostic, and therapeutic strategies against group B streptococci are pursued.

Paul Mathew, M.D.
Mayo Clinic, Rochester, MN 55905

4 References

1. 1

   Farley MM, Harvey RC, Stull T, et al. A population-based assessment of invasive disease due to group B streptococcus in nonpregnant adults. N Engl J Med 1993;328:1807-1811
   Full Text | Web of Science | Medline

2. 2

   Wessels MR, Kasper DL. The changing spectrum of group B streptococcal disease. N Engl J Med 1993;328:1843-1844
   Full Text | Web of Science | Medline

3. 3

   Anthony BF, Carter JA, Eisenstadt R, Rimer DG. Isolation of group B streptococci from the proximal small intestine of adults. J Infect Dis 1983;147:776-776
   CrossRef | Web of Science | Medline

4. 4

   Dillon HC Jr, Gray E, Pass MA, Gray BM. Anorectal and vaginal carriage of group B streptococci during pregnancy. J Infect Dis 1982;145:794-799
   CrossRef | Web of Science | Medline

To the Editor:

Farley et al. found a 21 percent in-hospital mortality rate associated with group B streptococcal infections and a rising incidence of such infections. The authors and the accompanying editorial by Wessels and Kasper argue that a vaccine against group B streptococci should be developed for use in nonpregnant adults. Their only qualification is that we need to be sure that the vaccine will elicit a sufficient antibody response. The authors and the editorialist have overlooked a more important question.

We are not given the expected survival of the hospitalized patients. There is much to suggest that they were severely, perhaps even morbidly, ill. Sixty-one percent of the patients in the study had diabetes, dementia, cerebrovascular disease, paraplegia, or quadriplegia. Fifty percent had renal failure, cancer, or liver disease. Many had a number of underlying conditions. The severity of base-line illness of this population is underscored by the frequency of polymicrobial sepsis (31 percent, or 42 of 137). Before spending millions to develop a vaccine to prevent a single type of infection, we need to be reasonably sure that these patients would benefit from an effective vaccine (i.e., would live longer or better) rather than die of some other terminal event.

Vaccine development for group B streptococcal infections in nonpregnant adults must be placed in the broader context of priorities in health care spending. We need to be reassured that other interventions, such as general improvement in access to care in the inner city, would not be more beneficial. These priorities should be based on the expected marginal benefit to the patient in relation to the expected additional cost of the solution.

Amy C. Justice, M.D.
University of Pennsylvania Medical Center, Philadelphia, PA 19104-6095

Author/Editor Response

The authors reply:

To the Editor: We understand Dr. Justice's concern about the need to set priorities in health care spending. If one were considering developing a group B streptococcal vaccine solely for use in adults, a complete assessment of cost and benefit would be appropriate. However, group B streptococcal vaccines may soon be available for the prevention of neonatal and pregnancy-related disease1. Although the cost of this work is substantial, the Institute of Medicine concluded in 1985 that such efforts would result in considerable savings in the health care dollars currently used to treat acute infections and, in some cases, lifelong sequelae2. Our study documents the substantial and possibly increasing incidence of invasive group B streptococcal disease among nonpregnant adults, especially the elderly and those with chronic diseases3. Because group B streptococcal vaccines are being developed, we believe that expanding the target groups to include adults at high risk clearly warrants further study. Although cost-benefit analysis is valuable for all public health decisions, it was not the purpose of our study. We found that most adults with group B streptococcal disease do have serious underlying conditions, some of which are ultimately fatal. However, one explanation for the increasing incidence of group B streptococcal disease in adults is the improved survival of adults with chronic diseases, such as diabetes mellitus4.

We agree with Dr. Mathew that there is great diversity among patients with cancer with regard to immune-system defects. The clarification of risk factors for group B streptococcal disease and further definition of host defects are important. We are currently conducting a multicenter case-control study in adults of risk factors for invasive group B streptococcal disease in an effort to address these issues more completely.

We are happy to provide additional clinical information on the patients described in our article3. Among the 23 patients with malignant neoplasms, 12 were undergoing chemotherapy, radiation therapy, or both (this group included all 6 patients 20 to 49 years old, 5 of the 11 patients 50 to 69 years old, and 1 of the 6 patients 70 years old or older). Five patients had neutropenia, and two had gastrointestinal cancers. Ten of the 23 patients with malignant neoplasms had advanced or end-stage disease. Eleven percent of the patients with invasive group B streptococcal disease (15 of 137) had concomitant gram-negative sepsis, enterococcal sepsis, or both; 7 of them died.

Although many patients with group B streptococcal disease have serious underlying conditions, most are not immediately fatal and the prevention of infection may substantially prolong life. Further studies are needed to define the problem of group B streptococcal disease in adults better and to identify the best methods of disease prevention.

Monica M. Farley, M.D.
David S. Stephens, M.D.
Emory University School of Medicine, Atlanta, GA 30322

Jay D. Wenger, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333

4 References

1. 1

   Noya FJ, Baker CJ. Prevention of group B streptococcal infection. Infect Dis Clin North Am 1992;6:41-55
   Web of Science | Medline

2. 2

   Appendix P. In: Institute of Medicine, National Academy of Sciences. New vaccine development: establishing priorities. Diseases of importance in the United States. Vol. 1. Washington, D.C.: National Academy Press, 1985:242.
   

3. 3

   Farley MM, Harvey RC, Stull T, et al. A population-based assessment of invasive disease due to group B streptococcus in nonpregnant adults. N Engl J Med 1993;328:1807-1811
   Full Text | Web of Science | Medline

4. 4

   Centers for Disease Control and Prevention. Diabetes surveillance, 1991. Washington, D.C.: Department of Health and Human Services, 1992:60-3.
   

Author/Editor Response

We recognize that patients with cancer have a variety of defects in immune defenses, more than one of which may play a part in susceptibility to group B streptococcal infection. More detailed epidemiologic study of patients with cancer who have group B streptococcal infection may identify a subgroup of people at particular risk. We agree with Dr. Mathew about the importance of defining immune defects that predispose adult patients to group B streptococcal infection. The identification of groups at increased risk (patients with diabetes mellitus, cancer, or human immunodeficiency virus infection) by Farley et al. does not define specific defects in host immunity but suggests that such defects may be uncovered by future laboratory investigations. We reiterate our conclusion, that further investigation of the epidemiology and pathogenesis of group B streptococcal infection in adults is needed before we can develop a rational approach to prevention.

Michael R. Wessels, M.D.
Brigham and Women's Hospital, Boston, MA 02115

Dennis L. Kasper, M.D.
Beth Israel Hospital, Boston, MA 02215

Citing Articles (1)

Citing Articles

1. 1

   Onsi W. Kamel, Matthijs Van De Run, Matthew M. Hanasono, Roger A. Warnke. (1995) Immunosuppression-Associated Lymphoproliferative Disorders in Rheumatic Patients. Leukemia & Lymphoma 16:5-6, 363-369
   CrossRef