Toxigenic Corynebacterium diphtheriae -- Northern Plains Indian Community, August-October 1996

Diphtheria was one of the most common causes of death among children during the prevaccine era. In 1921, a total of 206,939 cases of diphtheria were reported in the United States (incidence rate: 190 cases per 100,000 population), including 15,520 deaths (case-fatality rate: 7.5%). Since the introduction and widespread use of diphtheria toxoid beginning in the 1920s, respiratory diphtheria has been well controlled in the United States. However, diphtheria remained endemic in some states through the 1970s, with reported incidence rates of greater than 1.0 per million population in six states (Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington) (1 ). Since 1980, only respiratory diphtheria has been reportable in the United States. During 1980-1995, a total of 41 respiratory diphtheria cases were reported (2); of these, four (10%) were fatal, and all occurred in unvaccinated children. Five of the six culture-positive diphtheria cases reported in the United States since 1988 have been associated with importation of Corynebacterium diphtheriae, an organism believed to have become rare or to have disappeared from the United States. This report describes a case of infection with toxigenic C. diphtheriae in an American Indian woman and presents the results of enhanced surveillance for diphtheria in the surrounding community. The findings suggest that C. diphtheriae continues to circulate in areas of the United States with previously endemic diphtheria. Case Report

On June 1, 1996, a 62-year-old American Indian woman with a history of alcoholism and severe necrotizing skin ulcers on both legs was admitted to an Indian Health Service (IHS) hospital in South Dakota for treatment of alcohol intoxication and infected leg ulcers. She was treated with a course of ampicillin and received split-thickness skin grafts on both legs; she was discharged on June 19. A blood culture obtained from the patient on June 1 was sent to a regional reference laboratory, and C. diphtheriae, biotype mitis, was identified. At CDC's Diphtheria Laboratory, this isolate demonstrated weak toxigenicity. On admission, the patient's skin ulcers and throat were not swabbed. The patient had received a dose of adult formulation tetanus and diphtheria toxoid vaccine (Td) in 1984 and may have received an additional dose in 1994. Enhanced Surveillance

In response to isolation of this organism, the South Dakota Department of Health (SDDOH), the Aberdeen Area Office of the IHS, and CDC initiated enhanced surveillance to evaluate the possibility of C. diphtheriae infections among other persons in the community where the patient lived. During August 1-October 7, all persons presenting to the IHS hospital and three satellite clinics for evaluation of pharyngitis, draining middle-ear infections, or skin ulcers were cultured for C. diphtheriae as part of their routine clinical care.

Specimens were obtained from 133 patients. Of the 133 swabs, 113 (85%) were collected from the oropharynx, 13 (10%) from skin ulcers or wounds, and seven (5%) from ear drainage. C. diphtheriae was isolated from the swabs from six (5%) of the 133 patients (Table_1). Ages of the six patients with culture-positive results ranged from 3 to 60 years; four were school-aged children (aged 6-15 years). Three were females. Five of the six patients reported sore throat, and one patient presented with otitis media. In one of the patients with culture-positive results (a 15-year-old female), a pharyngeal membrane was present at the time of her initial presentation. Five patients had been fully vaccinated with diphtheria toxoid, and one 8-year-old child had received three doses of diphtheria and tetanus toxoids and pertussis vaccine (DTP). In addition to C. diphtheriae, three patients had culture-positive test results for beta-hemolytic Streptococcus (one each of Group A, Group C, and Group G), and one patient had culture-positive test results for C. pseudodiphtheriticum. All six patients were treated with penicillin or a cephalosporin.

The primary-care providers of the six patients with culture-positive results were informed about surveillance findings, and local public health nurses and SDDOH staff investigated the household contacts of all these patients. Of the 14 household contacts from whom cultures were obtained, C. diphtheriae was isolated from four (29%) (Table_2). Three of the six patients had household contacts who had culture-positive test results. In two households, multiple C. diphtheriae biotypes were isolated from family members. Household contacts received postexposure prophylaxis with penicillin and a dose of diphtheria toxoid-containing vaccine, regardless of their infection status. Laboratory Results

Of the 10 positive isolates obtained from the six patients and the four household contacts, nine were from throat cultures, and one was from ear drainage. Eight isolates demonstrated toxigenicity by the Elek immunoprecipitation test and by poly-merase chain reaction testing (PCR), which can detect both A and B subunits of the diphtheria toxin gene, tox. Of the 10 isolates, five were of the biotype mitis, and five were gravis. The toxigenic isolates were assayed by ribotyping and multilocus enzyme electrophoresis and compared with 10 C. diphtheriae isolates obtained from other patients in the same area during 1979-1983. Both molecular methods indicated that recent and older isolates from this area were genetically closely related to each other and differed from C. diphtheriae strains isolated either from other regions of the United States or from countries of the former Soviet Union affected by the ongoing diphtheria epidemic (3).

Reported by: T Welty, MD, C La Fromboise, MPH, J Dixon, DO, A Hurst, MD, D Mulder, DO, M Apostol, M Afraid of Bear, Aberdeen Area Office, Indian Health Service; L Volmer, L Schaeffer, W Anderson, J Judson, S Lance, DVM, State Epidemiologist, South Dakota State Dept of Health. Diphtheria Laboratory, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; Infant Immunization Activity, Child Vaccine Preventable Disease Br, Epidemiology and Surveillance Div, National Immunization Program, CDC.

Editorial Note

Editorial Note: During August-October 1996, six (5%) persons in an American Indian community in South Dakota were infected with C. diphtheriae; isolates from four of these persons were toxigenic. During 1971-1981, South Dakota had the highest average annual incidence (12.4 cases per million) of diphtheria (1). Molecular analysis suggests continuous presence of the organism in this community despite the absence of reported cases since 1976. The presence of two different biotypes in the same household suggests high rates of infection in the population.

The absence of reported cases of respiratory diphtheria in this South Dakota community since the late 1970s suggests a high level of vaccine-related or natural immunity in the population. The extent to which the pharyngitis in these patients was caused by C. diphtheriae or by other pathogens cannot be determined. Further evaluations are under way in the community to define factors associated with endemicity of C. diphtheriae, assess DTP vaccination coverage among children, and determine seroprevalence of diphtheria antibody among adults.

The presence of toxigenic C. diphtheriae in this community underscores the need to reemphasize the importance of timely vaccination against diphtheria among persons of all ages in the United States. Other Corynebacterium species may rarely produce diphtheria toxin but still cause a diphtheria-like disease in humans that is preventable through vaccination (4). Completing the routinely recommended childhood vaccination series for DTP (i.e., five doses at the recommended ages) and achieving high vaccination levels (greater than 90%) among preschool-aged children is of particular importance in this community and in other communities where diphtheria was previously endemic. In addition, booster doses of Td vaccine every 10 years are recommended throughout adulthood. Efforts are under way to educate the public and health-care providers about the importance of vaccinations. Finally, surveillance should be enhanced in areas where diphtheria was previously endemic. Clinicians should consider diphtheria in the differential diagnosis of patients presenting with a sore throat; low-grade fever; and an adherent membrane of the tonsil(s), pharynx, and/or nose. Because the successful isolation of C. diphtheriae depends on rapid inoculation of special culture media, the laboratory should be notified as soon as the diagnosis is suspected. Whenever a diagnosis of diphtheria is strongly suspected, local public health officials should be notified immediately, and measures to prevent additional cases should be instituted (5).

As of January 1997, diphtheria antitoxin is no longer commercially available in the United States but may be obtained for treatment of suspected cases of diphtheria through the medical epidemiology staff of CDC's Child Vaccine Preventable Disease Branch, Epidemiology and Surveillance Division, National Immunization Program, telephone (404) 639-2889 (6).

References

1. Chen RT, Broome CV, Weinstein RA, Weaver R, Tsai TF. Diphtheria in the United States, 1971-81. Am J Public Health 1985;75:1393-7.

2. Bisgard KM, Hardy IRB, Popovic T, Strebel PM, Wharton M, Hadler SC. Virtual elimination of respiratory diphtheria in the United States {Abstract no. G12}. In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1995:160.

3. CDC. Update: diphtheria epidemic -- New Independent States of the Former Soviet Union, January 1995-March 1996. MMWR 1996;45:693-7.

4. CDC. Respiratory diphtheria caused by Corynebacterium ulcerans -- Terre Haute, Indiana, 1996. MMWR 1997;46:330-6.

5. Farizo KM, Strebel PM, Chen RT, Kimbler A, Cleary TJ, Cochi SL. Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control. Clin Infect Dis 1993;16:59-68.

6. CDC. Availability of diphtheria antitoxin through an investigational new drug protocol. MMWR 1997;46:380.

TABLE 1. Patients with Corynebacterium diphtheriae  isolates -- Northern Plains Indian community, August-October 1996
========================================================================================================================================
Patient          Symptoms                               Age (yrs)    Sex    Site of specimen collection     Biotype   Toxigenicity
----------------------------------------------------------------------------------------------------------------------------------------
Index patient    Leg ulcers                                    61      F               Blood                 Mitis    Weakly toxigenic
   1             Pharyngitis, labored breathing                 3      F              Throat                 Mitis    Weakly toxigenic
   2             Suppurative otitis media                       8      M                Ear                 Gravis    Nontoxigenic
   3             Exudative pharyngitis                          8      M              Throat                Gravis    Toxigenic
   4             Pharyngitis with   membrane                   15      F              Throat                 Mitis    Toxigenic
   5             Exudative tonsillitis                         60      M              Throat                Gravis    Toxigenic
   6             Tonsillitis, pharyngitis, fever                7      F              Throat                Gravis    Nontoxigenic
========================================================================================================================================

TABLE 2. Household contacts with Corynebacterium diphtheriae isolates -- Northern Plains Indian community, August-October 1996
================================================================================================================================
Contact    Relation to patients         Age (yrs)    Sex    Site of specimen collection     Biotype    Toxigenicity
--------------------------------------------------------------------------------------------------------------------------------
   1       Mother of patient 1             30         F                Throat                Gravis    Toxigenic
   2       Sibling of patient 3            13         F                Throat                Mitis     Weakly toxigenic
   3       Sibling of patient 3            11         F                Throat                Mitis     Toxigenic
   4       Sibling of patient 4            13         M                Throat                Mitis     Toxigenic
================================================================================================================================

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