Scientific Papers

Human rabies encephalomyelitis in the background of rabies outbreak in animals in Gelephu, Bhutan, 2023: a case report | Infectious Diseases of Poverty

History and examination

A 35-year-old male presented to our hospital in June 2023 with intermittent fever for 4 days, and bilateral lower limb weakness for 3 days that was sub-acute in onset, progressive with patient becoming bed-bound within 1 day. He had sensation of bladder filling but was unable to void urine. He also had episodes of palpitations and excessive sweating and nausea. There was no tightness or looseness of limbs, no cough, chest pain, abdominal pain, seizures or loss of consciousness.

Twenty-five days prior to admission, the patient had history of dog bite above the right knee resulting in deep laceration on both medial and lateral aspects of the lower thigh. The dog bite happened in Tareythang, a settlement located along the Bhutan-India international border (Fig. 1). The patient had received anti-rabies virus post-exposure prophylaxis, intra-dermal injections (Day 0, 3, and 7) and tetanus toxoid. The dog had bitten four cats (all died due to injuries) and two cows (both died later and one tested positive for rabies using a rapid test kit and fluorescent antibody test on brain sample). The dog was not a native of the place and was chased away, its status unknown.

Fig. 1
figure 1

Map of Bhutan showing the border town of Gelephu, the settlement in Tareythang and the Central Regional Referral Hospital (CRRH) where a 35-year-old male for rabies encephalomyelitis was treated in June–July 2023

On initial examination, he was oriented and following instructions, had temperature 38.7 ℃, pulse rate 60–100/min (variable), blood pressure 110/80 mmHg, respiratory rate 22/min, SpO2 98% on room air, random blood glucose 6.9 mmol/L. No pallor, icterus, cyanosis, clubbing, oedema. Goose skin on the anterior aspect of left thigh. He had a bite mark with black healing scar 1 cm on medial side, bite marks with healing lacerations on lateral side of the right thigh, just above the knee joint. The dog bite wound was dry with no evidence of secondary infection (Fig. 2).

Fig. 2
figure 2

Wounds from a bite from an unknown dog, 25 days prior to admission, in a 35-year-old male with rabies encephalomyelitis. a Lateral aspect of lower end of right thigh with three healed lacerations. b Medial aspect of right lower end of thigh with one deep puncture wound with healing scab

Cardiovascular system: S1 S2 normal. Respiratory system: bilateral vesicular breaths. Abdomen: soft, non-tender, no organomegaly, bowel sounds present. Nervous system: higher mental function—oriented to time, place, person. No cranial nerve deficits, no neck stiffness. Aerophobia and hydrophobia present. Spontaneous fasciculations in bilateral thigh and right forearm. Upper limbs: tone normal, bulk normal, power 5 in both proximal and distal muscles. Lower limbs: hypotonia in bilateral lower limbs, power 0 in right lower limb, power 1 in left lower limb. Reflexes: normal in bilateral biceps, triceps and supinator. Bilateral knee joint and ankle joint reflexes absent. Bilateral plantar reflexes flexor. Abdominal reflexes absent below umbilicus. Sensory examination: Hyperasthesia from T8 downwards. Touch, vibration (128 Hz), joint position sensation intact.

Laboratory diagnosis

The findings of the investigations over the course of hospital admission are summarized in Table 1. Polymerase chain reaction for rabies virus in saliva and cerebrospinal fluid tested in Bengaluru, India through the help of the national reference laboratory in Bhutan, were negative. Rabies virus neutralizing antibodies in the cerebrospinal fluid was negative. High titres of rabies virus neutralizing antibodies were found in the serum.

Table 1 Summary of investigation findings of a 35-year-old male treated for probable rabies encephalomyelitis at the Central Regional Referral Hospital, Gelephu, Bhutan, 2023

Rabies management

Based on the clinical features and the ongoing rabies virus outbreak in the locality, this case was managed as a case of encephalomyelitis secondary to rabies virus infection. The case was admitted to the Isolation Room in the Intensive Care Unit. Given that this was a Category III bite, Human Rabies Immunoglobulin was given (intramuscular injection 20 units/kg) as local infiltration around the bite site and the patient completed the Anti-rabies Virus vaccine (Day 28) after admission.

The patient had a progressive course with altered sensorium, visual hallucinations, photophobia with restlessness with fasciculations involving the intercostal and neck muscles. He also had several episodes of generalized seizures on the night of admission. The patient had worsening of respiratory function and desaturation for which he was intubated and put on mechanical ventilator. For the initial 3 days, he had Glasgow Coma Scale score 7T with episodes of autonomic dysfunction with palpitations, raised blood pressure and diaphoresis and was sedated with Phenobarbitone. From day 4 onwards, his brain stem reflexes were absent.

Even though evaluation were not suggestive of other aetiologies, the patient received antibacterial (Ceftriaxone 2 g iv q12h and Ampicillin 2 g iv q6h) and antiviral agent (Acyclovir 500 mg iv q8h) for 14 days for empirical coverage. A trial of Ribavirin (1 g q12h via nasogastric tube) was administered from day 12 onwards, but was withheld after 4 days with the development of non-oliguric acute kidney injury.

The patient was managed with supportive nursing care. He had fever with hypotension for 2 days that was followed by refractory shock despite the vasopressors (noradrenaline 250 μg/min iv and adrenaline 160 μg/min iv). He survived three events of cardiac arrests and died after 23 days.

As per the Bhutan National Management Guideline for Rabies 2014, the case was reported to the National Early Warning, Alert Response Surveillance and Information System and the District Livestock Office was alerted. A rapid response team from the district deployed and uncovered a rabies outbreak in three dogs, three cattle, two cats and one rabbit in the locality.

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