The girl’s exposure occurred through an unidentified bat bite on her right elbow that produced a punctate lesion. This lesion was the initial focus of the disease, as the virus contained in the bat’s saliva crossed the neuromuscular junctions to the peripheral nerves and used retrograde axonal transport to reach the girl’s central nervous system. Children from this tribe have a cultural habit of playing with these animals, a behavior that exposes this population to a greater risk of contracting human rabies. Carrying out health education actions in view of the close relationship of the Maxakali people with animals with potential for transmission is an essential measure to break the epidemiological chain of this anthropozoonosis in this vulnerable population group with the aim of identifying potential sources and routes of transmission, assisting in preventive measures for future cases.

It is noteworthy that there was greater survival of this child compared to other cases, possibly due to the greater distance between the site of virus inoculation (right elbow region) and the central nervous system; and also due to the action of the antivirals used, which may have contained the rapid spread of the rabies virus [7]. Even so, it is considered that antiviral treatment should have been administered at the beginning of the clinical course of the disease, at a stage when the virus had not yet reached the CNS. In this case, the administration of antiviral therapy was instituted nine days after the appearance of the first symptoms and seven days before diagnostic confirmation. The Milwaukee Protocol recommends that antiviral medication can be administered within 5 days of unavailability of rabies diagnosis [9]. The best option for treating rabies is still vaccination associated with immunoglobulin, both applied early in relation to contact with an animal carrying the virus. When this therapeutic approach is not carried out, the available medications are inefficient in blocking the progression of the disease [10].

The most common symptoms were headache and fever. The neurological phase compatible with the symptoms presented was paralytic, typical of cases transmitted by bats. The child received three doses of the inactivated rabies vaccine of cell culture in a post-exposure scheme and also equine rabies immunoglobulin in a hospital environment when the Recife Protocol had not yet started. The human rabies vaccine and immunoglobulin are contraindicated by both protocols [5]. But this combination has been used in some reports, most as prophylactic measures after exposure and before the onset of symptoms. There are case reports of patients who survived rabies, receiving rabies vaccination and immunoglobulin even after the onset of symptoms. Perhaps immunoglobulin, when applied at the onset of symptoms, preferably during the period of centripetal migration of the virus to the dorsal nerve roots, could be important in treating the disease [5].

The patient was taken with clinical and epidemiological suspicion of rabies from the local reference hospital to the state hospital reference for rabies treatment in an intensive care unit. She was placed in contact isolation, using appropriate personal protective equipment, central venous access, indwelling bladder catheterization and nasoenteral catheterization, ventilatory support, sedation to adapt to mechanical ventilation and monitoring with a sedation scale (Ramsey). In addition, monitoring of peripheral oxygen saturation, airway plateau pressure, maintenance of diuresis with adequate hydration, avoiding the use of diuretics and measuring core temperature and maintaining the environmental temperature controlled with drugs and superficial cooling [5]. After laboratory confirmation of rabies, all the procedures described above were maintained, in addition to the introduction of amantadine and sapropterin, as an equivalent of biopterin.

Nevertheless, when the vaccine or rabies immunoglobulin is administered to a patient with the disease, as occurred in this child, even though they are capable of stimulating the production of antibodies, such immunization agents are not sufficient to alter the evolution of the disease in patients who already have the disease [4, 11]. The early death may occur because the vaccine or immunoglobulin is from different strains than the wild virus to which the patient was exposed. Rabies vaccines are generally made with different strains of the virus, aiming for a robust immune response [12].

However, there are reports of nine cases of surviving patients, of which only one did not receive post-accident prophylaxis, considering the vaccine or immunoglobulin as prophylaxis. This information contradicts the opinion of the two protocols mentioned above, that vaccines and immunoglobulins are not recommended because they can reduce mortality from the disease [5]. There are those who believe that early antiviral treatment could result in better survival from the disease, which occurred in the case of this indigenous child, but not in the other cases consulted. Patients who received treatment and medical support within just two days of the onset of symptoms, using ketamine and amantadine, still did not recover [13].

Cerebral vasospasm has also been associated with complications in patients with rabies. Although transcranial Doppler was not performed in the case of this child, both protocols recommend it daily to evaluate this complication. In the Milwaukee Protocol, the recommendation is to perform transorbital ultrasound in cases of intracranial hypertension. As a preventive measure against cerebral vasospasm in this child, sapropterin was used. Vasospasm in cases of rabies is caused by a deficiency of tetrahydrobiopterin (BH4), essential for the synthesis of neural nitrous oxide, an important cerebral vasodilator [14].

The Recife Protocol establishes that biopterin must be used as soon as a diagnosis of rabies is suspected. The Milwaukee Protocol establishes that sapropterin should be prescribed from the fifth day of hospitalization, as this period is characterized by a greater risk of vasospasm and related complications. In the Brazilian protocol, BH4 dosage is recommended to evaluate biopterin activity at two moments, on the fifteenth day of hospitalization and 15 days after replacement at the maximum dose [5].

As they did not have biopterin, sapropterin was made available. Both sapropterin and amantadine were part of the child’s antiviral treatment. Amantadine is a synthetic antiviral agent that can inhibit viral replication in cells and is also a weak NMDA receptor (N-methyl D-aspartate receptor) and non-competitive antagonist that accelerates channel closure during ring block channelization [15].

A severe immune response in this child’s central nervous system may have caused the brain damage and dysfunction shown by brain CT, contributing decisively to the worsening of her condition. In an attempt to prevent or reverse cerebral edema, a new dose of equine rabies immunoglobulin was administered, but unfortunately this action did not have the expected effect in improving her health status. This type of brain damage causes the release of nitric oxide, considered a substance related to neurotoxin [16].

As the Maxakali indigenous population generally has a very vulnerable immune system, due to their previous pathological history and the poor sanitary conditions of their environment, the aforementioned child was from a risk group with greater susceptibility to infections, especially rabies. Studies by Hutz and collaborators [17] have indicated that Brazilian indigenous have a frequency of certain variations in genes in the immune system that make their immune response less efficient to viral infections.

The child’s clinical condition rapidly worsened with sweating, difficulty breathing, tachycardia and fever. And over the course of five days it developed into sialorrhea and absence of reflexes. Within three days, tachycardia, hypotension and septic shock worsened. After two days, the serious condition persisted, with tachycardia, bradycardia and fever spikes, and at the end of four days, she died. The clinical picture generally rapidly deteriorates the host’s health and leads to death from respiratory or cardiac failure in approximately seven to ten days. Some unusual examples of survival have been reported in humans, but the interventions have not been shown to be repeatable [18].

The Milwaukee and Recife Protocols are similar in terms of care related to patients with rabies and are important for the treatment of patients in intensive care units. Both indicate deep sedation, use of antivirals, constant concern with electrolyte balance and vasoconstriction related to the clinical picture [5]. The Recife protocol implemented in this case represented at least the possibility of greater survival for this native child, enabling more appropriate and dignified palliative care, seeking to minimize all the suffering of the patient and her family.

The Milwaukee Protocol highlights hyponatremia as a possible complication on the fifth day of hospitalization, and the use of prophylactic fludrocortisone may be indicated. The protocol points out that one of the causes of this disorder may be dehydration. This change may contribute to worsening brain injury, so recurrent sodium dosage is important. Both protocols recommend that serum sodium dosage should be performed twice a day [5].

Another differing point in the protocols refers to sedation withdrawal. In the Milwaukee Protocol, sedation should be gradually removed after the eighth day, and on the twelfth day, the patient should be without sedation. In the Recife Protocol, in order to avoid immunomodulation, it is recommended to remove sedation according to the titers of neutralizing antibodies to the RABV in the cerebral spinal fluid. Specific rabies tests (serology and polymerase chain reaction [PCR]) are indicated repeatedly in both protocols. BH4 dosage is described in the Recife Protocol; this substance is associated with cerebral vasospasm in an angry patient. The Recife Protocol recommends the prophylactic use of biopterin, which must be maintained for four to six months, followed by a new dose of BH4 in the cerebrospinal fluid (CSF [5].

On the other hand, there is criticism regarding the use of both protocols, under the pretext that the majority of survivors receive post-exposure prophylaxis with one or more doses of rabies vaccine [19]. Documented rabies survivors, at least in part, represent advances in cardiorespiratory supports in modern intensive care units and may not be related to specific rabies-directed therapies.

A limitation of this report is the lack of detailed immunological data that could provide an additional immunological marker of RABV clearance. This may be explained by the lack of experience of the medical team in managing rabies cases, coupled with the lack of incorporation of these protocols into the Brazilian hospital medical routine due to the controversy over their use, which often requires the collaboration of international medical experts to guide the implementation of this experimental treatment.

It is concluded that the Milwaukee Protocol requires a greater treatment structure for rabies with denser technological health resources, and as most of the time the disease occurs in regions with scarce resources, this protocol is generally not adopted, or when it is, many is sometimes discontinued.