Date: Wed 29 Mar 2023

Source: Clinical Infectious Diseases [edited]

情報源: Clinical Infectious Diseases(編集)

ref: Holzbauer SM, Schrodt CA, Prabhu RM, et al. Fatal human rabies infection with suspected host-mediated failure of post-exposure prophylaxis following a recognized zoonotic exposure -- Minnesota, 2021. Clin Infect Dis. 2023; ciad098.

参考:Holzbauer SM, Schrodt CA, Prabhu RM, et al.


   Clin Infect Dis. 2023; ciad098.


Background: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84 year old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection.
背景 :現代の細胞培養ワクチンを用いている合衆国では、人において狂犬病曝露後予防(PEP)の失敗した記録がない。2021年1月、84歳の男性が、適時に狂犬病曝露後予防(PEP)を受けたにもかかわらず、狂犬病のコウモリに咬まれてから6カ月後に狂犬病で死亡した。我々は、ブレークスルー感染の原因を調査した。

Methods: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient.
方法: 医療記録、検査結果、剖検所見を検討し、全ゲノム配列決定(WGS)を行い、患者およびコウモリのウイルス配列を比較した。患者に投与されたPEP生物製剤の保管、投与方法について完全であったかを評価し、残存する狂犬病免疫グロブリンのサンプルの効力を評価した。コウモリに暴露される可能性のある人および患者の濃厚接触者についてリスク評価を行った。

Results: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP.
結果 :血清および脳脊髄液に存在する狂犬病ウイルス抗体は非中和性であった。死後の血液検査で、認識されていなかった意義不明の単クローン性ガンマグロブリン血症(訳者注:形質細胞が単一の種類の 抗体を大量に生産する病気。通常症状はなく治療の必要はないが、他の抗体の産生が少なくなり易感染性が見られることがある。70歳以上の人の5%以上に発生するとされる。)が認められた。剖検所見では、狂犬病髄膜脳炎と転移性前立腺腺癌が認められた。患者と当該コウモリの狂犬病ウイルス配列は、WGSにより同一であった。投与されたPEPの効力、品質管理、投与法、保管に問題は確認されなかった。狂犬病曝露の可能性を評価した332人のうち、PEPを必要としたのは3人(0.9%)であった。

Conclusion: This is the 1st reported failure of rabies PEP in the western hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.
結論 :細胞培養ワクチンを用いた狂犬病PEPの失敗例は、西半球で初めて報告された。ブレークスルー感染が認めらた本症例は、これまで認識されていなかった免疫力低下に起因する宿主関連性の一次ワクチンの失敗が原因である可能性が最も高いと考えられる。臨床医は、免疫不全が疑われる場合には、PEP終了後に狂犬病中和抗体価を測定することを検討する必要がある。
communicated by:

[Although this situation occurred in 2021, the article has only recently been published. While there are any number of reasons for the delay in publication, perhaps it was out of respect for the victim's family, as well as much investigation as to why this vaccine had what appears to be a failure.

The article suggests that the post-exposure prophylaxis (PEP) did not fail as such, but rather that an immunocompromised person was unable to mount a defense despite having PEP.

We remind our readers to take any issue with the rabies virus seriously. In the presence of bats, do not assume you were not bitten but rather assume you could have been or were bitten and may not know it. Their teeth are extremely sharp, and bites are very tiny and unfortunately can easily go unnoticed on the victim, especially if they are sleeping when the bite occurs.

If there is a chance you or someone associated with you could have been bitten, please seek medical attention immediately. - Mod.TG


ProMED map:
Minnesota, United States: https://promedmail.org/promed-post?place=8709345,354]

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