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CASE REPORT
Year : 2002  |  Volume : 20  |  Issue : 1  |  Page : 50-52
 

Diphtheria due to non-toxigenic corynebacterium diphtheriae: A report of two cases


Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry - 605 006, India

Correspondence Address:
Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry - 605 006, India

 ~ Abstract 

Diseases due to non-toxigenic strains of Corynebacterium diphtheriae are being increasingly reported. These diseases have been found to occur in vaccinated individuals. We report two cases of diphtheria with myocarditis and polyneuritis caused by non-toxigenic strains of C. diphtheriae. The virulence factors of this organism and the pitfalls in diagnosis have also been discussed.

How to cite this article:
Kanungo R, Vijayalakshmi N, Nalini P, Bhattacharya S. Diphtheria due to non-toxigenic corynebacterium diphtheriae: A report of two cases. Indian J Med Microbiol 2002;20:50-2


How to cite this URL:
Kanungo R, Vijayalakshmi N, Nalini P, Bhattacharya S. Diphtheria due to non-toxigenic corynebacterium diphtheriae: A report of two cases. Indian J Med Microbiol [serial online] 2002 [cited 2020 Oct 25];20:50-2. Available from: https://www.ijmm.org/text.asp?2002/20/1/50/8337


Both toxigenic and non-toxigenic strains of Corynebacterium diphtheriae are associated with disease. It is the toxigenic strain, which produces systemic manifestations like myocarditis, polyneuritis and focal necrosis of internal organs like liver, kidney, and adrenal glands.[1] Infections caused by non-toxigenic strains of C. diphtheriae have been reported to be associated with significant invasive diseases like endocarditis and septic arthritis.[1],[2],[3] However the pathogenesis of diseases caused by non-toxigenic C. diphtheriae is largely unknown. It has been postulated that non-toxigenic strains occur more frequently in individuals who have been previously immunized.[4] Here we report two cases of diphtheria caused by nontoxigenic C. diphtheriae.

 ~ Case reports Top

Case 1
A 10-year-old female child presented to the Pediatric emergency with history of fever, respiratory distress and stridor. On examination a grayish white patch was found on both the tonsils and the pharyngeal wall, extending to the larynx. She had tachycardia out of proportion to her fever. A prolonged PR interval with changes in the ST-T waves were noted on her electrocardiogram. The immunization history of the child was complete with two booster doses at 1.5 years and 5 years respectively. Examination of the throat swab revealed characteristic bacilli with metachromatic granules in cuneiform arrangement on Albert stain. Growth on potassium tellurite agar showed black colonies. The strain was identified by standard methods as C. diphtheriae biotype mitis.1 The patient was treated with anti-diphtheritic serum (ADS) and penicillin but expired within two hours of admission due to cardiorespiratory failure. Elek's gel precipitation test and guinea pig intradermal test done at the National Institute of Communicable Diseases (NICD), New Delhi, showed the strain to be non-toxigenic.
Case 2
A 10-year-old male child presented to the Pediatrics out patient clinic with high-grade fever and history of nasal regurgitation of fluids. On examination he was found to have grayish patch over the pharynx. Focal neurological deficits were observed resulting in paralysis of the soft palate. The cardiovascular system was found to be normal. Examination of the throat swab by Albert stain revealed green bacilli with metachromatic granules at the poles in cuneiform arrangement. On potassium tellurite agar black colonies were found which were identified as C. diphtheriae biotype gravis by standard microbiologic tests.1 The patient's immunization was incomplete with two primary doses only. He was treated with anti-diphtheritic serum and penicillin and recovered uneventfully with no neurological deficits. The toxigenicity tests of the C. diphtheriae strain done at NICD reported it to be non-toxigenic.

 ~ Discussion Top

Non-toxigenic strains of C. diphtheriae colonize the mucous membrane like the toxigenic strains. The invasive property of non-toxigenic C. diphtheriae seems to be determined by surface K antigens, the cord factors, and the enzymes neuraminidase and N-acetyl neuraminidase.1 The K antigens are heat labile proteins located on the superficial layer of the cell wall. The cord factors are toxic glycolipids containing mycolic acids characteristic of C. diphtheriae. Chemically these are 6-6' diesters of trehalose and consist of corynemycolic acid (C32H62O3), and corynemycolenic acid (C32H64O3). In mouse these cord factors have been found to cause disruption of the mitochondria, reduction of respiration, reduction of phosphorylation, and cell death. Neuraminidase and N-acetyl neuraminidase degrade N-acetyl neuraminic acid residues on the mucinous environment of the mucous membranes and provide readily available energy for bacteria.[1]
The diagnosis of C. diphtheriae has many potential pitfalls. Toxigenic and non-toxigenic strains of C. diphtheriae may exist in the throat at the same time.[5] Chang in 1978 had reported the simultaneous isolation of one non-toxigenic (phage type 7) and two toxigenic strains (phage type 7 and 11) of C. diphtheriae from the throat of a 25-year-old woman.[5] Groman in 1983 showed that 14/43 (32.5%) non-toxigenic isolates of C. diphtheriae (as detected by the gel diffusion and rabbit intracutaneous tests) carried DNA sequences for tox gene as detected by DNA probes.[6] Out of these 14 isolates, 12 produced ADP-ribosylating activity- a phenomenon that is considered the hallmark of diphtheria toxin.
Toxin mediated inhibition of protein synthesis is believed to be the essential prerequisite for systemic manifestations in diphtheria. In this context it is difficult to explain the occurrence of systemic manifestations like myocarditis and neuritis by non-toxigenic strains of C. diphtheriae. Co-infection with viruses may be an explanation. Although no viral etiology was established in this case it is interesting to note that clinical disease consistent with toxic diphtheria characterized by myocarditis and polyneuritis have been reported in association with non-toxigenic C. diphtheriae.[7] Moreover, it is possible that during the process of culture and toxigenicity testing only the non-toxigenic strain was detected as a combination of toxigenic and non-toxigenic strain existed in the same culture plate simultaneously.[5]
Toxigenic strains causing diphtheria in Russia and Ukraine in the 1990s have shown heterogenicity of the toxin gene 'tox' and its regulatory element 'dtxR'. This has been noted using single stranded conformational polymorphism (SSCP). SSCP patterns were also shown to differ from the Park William strain[8], which is used worldwide for vaccine production. It needs to be explored whether variation of the 'tox' gene and its regulatory element 'dtxR' has any inhibitory effect on diphtheria toxin production, and if the inhibitory effect is present what is its domain of action-in-vivo, in-vitro, or both. 

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