Correspondence

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American Journal of Emergency Medicine

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Considerations for tetanus infection in an adult with a protective tetanus antibody level?

To the Editor,

We read with interest the article titled “A case of tetanus infection in an adult with a protective tetanus antibody level” by Vollman et al [1]. The authors reported a mild case of tetanus infection despite a markedly higher protective antibody level (8.4 IU/mL). However, there are several serious concerns raised in the study.

First, the authors described that symptoms resolved after human tetanus immune globulin (TIG) administration. They reported that 13 hours after TIG administration, there was increased range of motion in the patient’s lower jaw and decreased neck pain. We note that there was no additional pharmacologic treatment and that approximately 27 hours after TIG administration, full range of motion returned to his neck, and he was able to move his jaw more completely. However, the authors themselves describe that TIG only neutralizes the unbound endotoxin produced by Clostridium tetani; it possess neither antibac- terial activity nor the capacity to prevent bacterial growth and cannot restore Organ function. The tetanus toxin initially binds to peripheral nerve terminals and causes the clinical symptoms [2]. Therefore, theoretically, TIG does not resolve clinical symptoms, and such assertions are likely to be incorrect. In our opinion, the prompt resolution of symptoms after TIG administration was unlikely to be the effect of TIG and was more likely to be a coincidence or placebo effect. Second, we would question the accuracy of the diagnosis of tetanus.

The diagnosis of tetanus is based on the clinical presentation of tetanus symptoms and is not dependent upon isolation of the bacterium. In the case presented, the patient indeed presented with tetanus-like symptoms, such as swallowing difficulty due to pain and jaw and neck pain. However, the patient also had an injected oropharynx with normal complete blood count and erythrocyte sedimentation rate on admission and recovered well without any onset of Autonomic instability. These latter findings are consistent with possible viral pharyngitis. Although positive objective results, such as the spatula test [3], isolation of the bacterium, laboratory data, and typical autonomic instability may confirm tetanus, we believe that possible tetanus is a more appropriate diagnosis given the limited detail.

Third, a previous report of severe tetanus in immunized patients with high tetanus antibody titers has identified a possible deficiency in the immune repertoire to tetanus neurotoxin [4]. The authors emphasized that even antitetanus antibody titers deemed adequate by in vitro measurement could be less than 0.01 U/mL when using in vivo mouse protection bioassays. In the present case, the tetanus antibody level was evaluated only by enzyme-linked immunosorbent assay. Therefore, the effectiveness of tetanus Antibody levels to neutralize tetanus neurotoxin at the higher level of 8.4 IU/mL remains unknown in the absence of in vivo mouse protection bioassays.

Our understanding of this case is that tetanus infection was suspected clinically because of the development of tetanus-like symptoms. However, the diagnosis of tetanus infection may be less likely given the very high antibody level and the limited case presentation.

Toru Hifumi, MD Kagawa University Hospital, 1750-1 Ikenobe Miki, Kita, Kagawa 761-0793, Japan

Corresponding author. 1750-1, Miki, Kita, Kagawa, 761-0793 Japan. Tel.:+81 87 891 2392; fax: +81 87 891 2393.

E-mail address: [email protected]

Akihiko Yamamoto, PhD National Institute for Infectious Disease, 4-7-1 Gakuen Musashimurayama, Tokyo 208-0011, Japan

Motohide Takahashi, PhD

Pharmaceuticals and Medical Devices Agency 3-3-2 Kasumigaseki, Chiyodaku, Tokyo, 100-0013, Japan

Yuichi Koido, MD National Hospital Organization Disaster Medical Center 3256 Midori, Tachikawa, Tokyo 190-0014, Japan

Kenya Kawakita, MD Yasuhiro Kuroda, MD

Kagawa University Hospital, 1750-1 Ikenobe Miki, Kita, Kagawa 761-0793, Japan

http://dx.doi.org/10.1016/j.ajem.2014.06.008

References

1. Vollman KE, Acquisto NM, Bodkin RP. A case of tetanus infection in an adult with a protective tetanus antibody level. Am J Emerg Med 2014;32:392.e3-4.
2. Infectious Disease Surveillance Center Center IDS. Tetanus in Japan as of 2001. http://idsc.nih.go.jp/iasr/23/263/tpc263.html.
3. Apte NM, Karnad DR. Short report: the spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg 1995;53:386-7.
4. Crone NE, Reder AT. Severe tetanus in immunized patients with high anti-tetanus titers. Neurology 1992;42:761-4.

   Response to considerations for tetanus infection in an adult with a protective tetanus

   

   antibody level?,??

   To the Editor,

   We thank Dr Hifumi et al for continuing discussion regarding our recent case report of tetanus infection despite a protective tetanus antibody level [1].

   ? Conflict of interest: None declared.

   ? Source of support: None.

   ?? Prior presentations: None.

   0735-6757/(C) 2014

   We agree with the authors that human tetanus immune globulin (TIG) neutralizes unbound tetanus toxin only. It was never the intent of our case report to claim that the improvement in symptoms experienced by the patient was secondary to TIG administration alone, as the patient did receive metronidazole therapy as well. Rather, the increased range of motion in his jaw and decreased neck pain are most likely due to the clearance of infection by the patient. However, we are convinced that the administration of TIG prevented the progression of infection. The patient endorsed jaw pain that progressed to an inability to close his mouth as well as neck pain that noticeably progressed throughout the day on the day of presentation to the emergency department (ED). Given the resolution of these symptoms, we believe that the TIG administered blunted the spread of the presumed active tetanus infection.

   The diagnosis of tetanus infection is based on clinical signs and symptoms and is often coupled with the exclusion of other differential diagnoses. His physical examination revealed tenderness to palpation over sternocleidomastoid muscles bilaterally, poor range of motion of the neck, pain on minimal lateral movement of the neck, and tenderness on palpation of the submandibular region bilaterally. He underwent extensive laboratory and radiographic examinations, which ruled out other causes for neck and jaw pain. He did receive a bacterial pharyngitis culture that was negative and a trial of benzodiazepines and diphenhydramine to rule out an adverse medication reaction and extrapyramidal symptoms. Furthermore, the patient was never febrile, and no tonsillar exudate was found upon examination. The patient did not endorse any sick contacts that would increase the suspicion of viral (or bacterial) pharyngitis. Although viral pharyngitis could not be ruled out, we feel that the Rapid resolution of symptoms makes this diagnosis unlikely, especially without receiving continued antiinflammatory therapy after the one-dose ketorolac administered in the ED.

   As we mentioned in our original case report, multiple cases have been published demonstrating the possibility of active tetanus infection despite a protective level of tetanus antibody [2-9]. Each of these cases reported antibody levels that were drawn before TIG administration. Given the previously published reports, in addition to our patient case, one can infer that antibodies may decrease the severity of tetanus infection, but there may exist a ratio of toxin to antibody that, if surpassed, may lead to active infection, no matter what the antibody level may be. We question the level of tetanus antibody considered “protective” whether the level is analyzed via enzyme-linked immuno- sorbent assay or in vivo mouse protection bioassay.

   Kristan E. Vollman, PharmD

   Department of Pharmacy University of Rochester Medical Center, Rochester, NY Corresponding author. Department of Pharmacy University of Rochester Medical Center, 601 Elmwood Ave

   Box 638, Rochester, NY 14642.

   E-mail address: [email protected]

   Nicole M. Acquisto, PharmD

   Department of Pharmacy University of Rochester Medical Center, Rochester, NY,

   Department of Emergency Medicine University of Rochester Medical Center, Rochester, NY

   Ryan P. Bodkin, MD, MBA

   Department of Emergency Medicine University of Rochester Medical Center, Rochester, NY

   http://dx.doi.org/10.1016/j.ajem.2014.06.009

   References

   Vollman KE, Acquisto NM, Bodkin RP. A case of tetanus infection in an adult with a protective tetanus antibody level. Am J Emerg Med 2014;32(4):392.e3-4.

5. Livorsi DJ, Eaton M, Glass J. Generalized tetanus despite prior vaccination and a protective level of anti-tetanus antibodies. Am J Med Sci 2010;339(2):200-1.
6. Atabek ME, Pirgon O. Tetanus in a fully immunized child. J Emerg Med 2005;29(3):345-6.
7. Berger SA, Cherubin CE, Nelson S, Levine L. Tetanus despite preexisting antitetanus antibody. JAMA 1978;240:769.
8. Passen EL, Andersen BR. Clinical tetanus despite a protective level of toxin-neutralizing

   antibody. JAMA 1986;255:1171-3.

   Crone N, Reder AT. Severe tetanus in immunized patients with high anti-tetanus titers. Neurology 1992;42:761-4.

9. Abrahamian FM, Pollack Jr CV, LoVecchio F, Nanda R, Carlson RW. Fatal tetanus in a drug abuser with “protective” antitetanus antibodies. J Emerg Med 2000;18:189-93.
10. de La Chapelle A, Lavabre O, Pinsard M, Delamonica J, Relyveld EH. Tetanus in a renal transplant recipient exhibiting the presence of circulating antitetanus antibodies by ELISA. Biomed Pharmacother 2002;56:208-10.
11. Beltran A, Go E, Haq M, Clarke HB, Zaman M, Recco RA. A case of clinical tetanus in a patient with protective antitetanus antibody level. South Med J 2007;100:83.

    Pitfalls of the ultrasound diagnosis of pneumothorax

    

    To the Editor,

    The case presentation by Aspler et al [1] seems to be biased by the lack of correspondence of the shown image; more importantly, it appears to display the limitations of thoracic ultrasound in the diagnosis of pneumothorax more than its merits.

    The “anterior left pneumothorax with underlying pulmonary contusion,” so carefully described by the authors, should be evident by the chest computed tomography , as published [1]. Unfortu- nately, what the visible image shows is a questionable partial and very small-diameter less than 1.0 cm-pneumothorax and a possible contusion of the lung, without obvious chest contusions or bone fractures, otherwise described by authors; it cannot be excluded that what is presented can be due to something else, that is, a different cause of lung consolidation.

    The authors explain that “Bedside ultrasound of this region revealed a double Lung point sign.” We would describe what we actually see in the video clip as “in the likely site of pleural-lung contusion there is an area of apparent consolidation with possible pleural adhesion, which, nonetheless, moves slightly; the reappear- ance of a more evident gliding is seen at the boundaries.” There is no good reason for confirming pneumothorax-it is not seen here and, if any, actually very small even by CT-only based on the lack of the pleural gliding.

    In our experience and as others reported elsewhere, because gliding is lacking all around a pleural adhesion area, a lung point appears in at least 1 point of these margins [2] but also (why not?) in 2 or 3. We would also address that, after the original and truly considerable reports published by Wernecke et al [3] and Targhetta et al [4], 25 years ago, the effective sensitivity and specificity of Lung ultrasound for the diagnosis of partial pneumothorax are highly questionable. This is due to the methodological limitations of the subsequent published studies, which substantially show a significant percentage of false-positive cases [5], that is, of cases without pleural gliding, a condition due to different and quite common causes [2].

    A misleading diagnosis can be detrimental, particularly in an emergency if it is likely that this discourages using other more reliable tools, which are usually available for the diagnosis of pneumothorax. Overall, it is not so certain that authors “provide the first case report of