Wilde, Henry MD, FACP; Hemachudha, Thiravat MD, FACP

To the Editors:

We compliment Caicedo et al¹ for their report “Virology, immunology, and pathology of human rabies” and their meticulous clinical and laboratory documentations. The child reported in their study experienced a cat bite and was infected with a vampire bat rabies virus variant. She exhibited an unusual hopeful sign: neutralizing antibodies against rabies in serum and CSF shortly after admission. Management was aggressive, initially applying most components of the so-called “Milwaukee protocol” including deep coma induction using high-dose anesthesia with barbiturates, midazolam and ketamine. This had previously been proven not beneficial using in vitro and in vivo models and has resulted in severe complications; presumably due to physiological dysregulation above what may be due to rabies encephalomyelitis alone.² Furthermore, it complicates normal intensive care unit treatment and does not add any benefits. Many treatment failures at institutions with adequate facilities have also documented this.³ The last modification of the “Milwaukee protocol” eliminated the use of barbiturates and ribavarin. It also added a statement that the use of sedation should be held temporarily if the electroencephalogram appears suppressed.⁴ Katamine and midazolam are the only remaining elements of the original ‘Milwaukee protocol”; thus making it similar, if not identical, to the current routine intensive care practices worldwide. The 2013 WHO expert consultation conference on rabies made it very clear that there is no proven therapy for human rabies. Any new procedures or drugs should be proven that it does not add potentially harmful risks for an already seriously ill patient.⁵ There is now a consensus opinion among rabies-experienced clinicians that rabies can no longer be considered as an invariably fatal disease. Rare natural human survivors have been documented and are also known to occur more frequently among other mammals. There are no evidence-based rabies treatment guidelines; and the term “Milwaukee protocol” should not be used instead of “provision of appropriate supportive care in an intensive care setting.” Once new drugs and clinical procedures that are promising become available, they should only be applied after appropriate institutional ethical committee approval.

Henry Wilde, MD, FACP

Thiravat Hemachudha, MD, FACP

Faculty of Medicine

King Chulalongkorn Memorial Hospital

WHO Collaborating Centre for Research and Training on Viral Zoonoses

Chulalongkorn University

Pathumwan, Bangkok, Thailand

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