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Journal of Neuroinfectious Diseases
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  • Case Report   
  • J Neuroinfect Dis 2022, Vol 13(1): 372
  • DOI: 10.4172/2314-7326.1000372

The Rare Case of a Human Rabies Survivor and the Comparative Study of All Documented Human Rabies Survivors Till 2021

Sumirini1*, Abhijit Acharya2, Bharat Veer Manchanda3 and Saloni Mehra4
1Department of Neurology, SOA IMS & SUM Hospital, Bhubaneswar, Odisha, India
2Department of Neurosurgery, SOA IMS & SUM Hospital, Bhubaneswar, Odisha, India
3Department of Medicine, Swami Vivekanda Subharti University, Meerut, Uttar Pradesh, India
4Department of Surgery, Swami Vivekanda Subharti University, Meerut, Uttar Pradesh, India
*Corresponding Author: Sumirini, Department of Neurology, SOA IMS & SUM Hospital, Bhubaneswar, Odisha, India, Tel: 8054871861, Email: sumirini@ymail.com

Received: 18-Jan-2022 / Manuscript No. JNID-22-51828 / Editor assigned: 20-Jan-2022 / PreQC No. JNID-22-51828(PQ) / Reviewed: 03-Feb-2022 / QC No. JNID-22-51828 / Revised: 07-Feb-2022 / Manuscript No. JNID-22-51828(R) / Published Date: 14-Feb-2022 DOI: 10.4172/2314-7326.1000372

Abstract

Derived from a Sanskrit synonym “Rabhas”, meaning “violence”, Rabies, is a violent outrageous infection of the brain1 recognised in Vedic Indian scriptures dating to a period as back as 1500 B.C. Very deadly, rabies has been described as ‘the dog accompanying The God Of Death’.

Rabies is a fatal zoonotic viral disease transmitted from mammals to humans, that’s characterised by an acute excitogenic encephalitis and generalised paresis.

With only 24 documented cases of survival worldwide, till date, post development of symptoms, we are hereby reporting another classical case of rabies, which underwent gradual recovery, with minimal neurological sequalae.

Keywords: Human rabies; List of survivors; Indian study; Rare case report; Milwaukee protocol; Largest comparative study

Keywords

Human rabies; List of survivors; Indian study; Rare case report; Milwaukee protocol; Largest comparative study

Introduction

Derived from a Sanskrit synonym “Rabhas”, meaning “violence”, Rabies, is a violent outrageous infection of the brain1 recognised in Vedic Indian scriptures dating to a period as back as 1500 B.C. Very deadly, rabies has been described as ‘the dog accompanying The God of Death’ [1].

Rabies is a fatal zoonotic viral disease transmitted from mammals to humans, that’s characterised by an acute excitogenic encephalitis and generalised paresis [2].

With about 99% of cases being dog bite mediated, almost any mammal (domesticated or wild) is capable of incubating and transmitting the virus. The Rhabdovirus (RABV), of Family Lyssavirus is responsible for around 59,000 deaths worldwide annually, accounting to more than 60% of the deaths within India, owing to its lesser surveillance because of not being categorized a notifiable disease [3].

With only 24 documented cases of survival worldwide, till date, post development of symptoms, we are hereby reporting another classical case of rabies, which underwent gradual recovery, with minimal neurological sequalae.

Case Report

Our case, hereby, is a young female, aged 33 years, who was brought to the Emergency Room, by her husband and relatives, at around midnight of 28th September 2017 [4].

Giving a prompt history of a wild animal (Indian Civet, Viverricula indica) bite on her right leg 18 days back, the patient was now brought to our hospital, with complaints of altered sensorium for past 5-6 hours, with gradual deterioration to generalized immobility and nonresponsiveness for past 2-3 hours [5]. The patient was brought from NICD (National Institute of Communicable diseases), New Delhi, where the clinical diagnosis of “Acute Rabies Viral Encephalitis” was made. The attendants were counselled there for an isolation room for the patient, with a fatal prognosis succeeding it [6]. Thus, well-aware of the outcome, the patient was brought by her husband, for the terminal hospice care and palliation.

Admitted with us under Intensive Care Unit, the patient was examined, elaborately. The patient was in an unconscious state, responding by wincing (but with no withdrawal) to deep painful stimulus [7]. Her blood pressure was 130/90 mmHg, heart rate was 126 bpm, pulse rate 124 bpm, with no irregularities. Her respiratory rate was 24/min and, she was afebrile with an axillary temperature of 98.4 degree Fahrenheit [8]. Her saturation, on a pulse oximeter, displayed 94% at room air, and there were no signs of any respiratory distress. Upon further examination, both her plantar reflexes (Babinski’s) were flexors, both her pupils were normal sized, sluggishly reactive [9]. There was no neck rigidity, but, all other deep and superficial reflexes were diminished. Tone of her muscles were intact, and power was not elicitable. There was no history or any finding suggestive or urinary or bowel incontinence.

Her chest was clear, with normal vesicular conducted sounds, and the heart sounds were normal. Her right leg’s lateral aspect had a wound, which was dressed antiseptically [10]. The wound, upon exposure, had multiple lacerations, imprinting the bite marks of the animal (mentioned above), each 2-3 cm deep, with localised surrounding rubor. Patient was catheterized for urine, keeping her sensorium in view. There was no history of any abnormal body movements, any frothing from mouth, tongue bite [11].

Upon retrograde history, her husband, who witnessed the incident had explained of an unprovoked bite by the animal, in the wake of light (around 5am IST) [12], which ferociously kept held on to the patient’s leg, until it was killed. Immediately, the patient was taken to a local physician, the wound was washed and antiseptically dressed [13]. The wound was bleeding actively. The patient was started on Anti-Rabies Vaccine (Rabipur/Verorab), within 4 hours of bite, along with a stat dose of Tetanus toxoid, and was immunised regularly, as per the WHO guidelines, on Days 0-3-7-14 thereafter [14]. No local immunoglobulins were given. The patient was brought home immediately, prescribed on symptomatic medications.

But, 3 Days post-Bite, the local (bite-site) residual pain , started aggravating , and the over next 4-5 days, the patient used to vividly explain , the radiation of pain, beginning from the leg extending to the chest, and then progressed to the head, manifesting as a severe headache by Day-9 post-bite and patient was admitted for the same in a local hospital [15]. The patient started developing anxiousness, restlessness, and could not sleep, until was sedated, 10th day onwards (post-bite). On Day 15 post-bite, patient developed fever (high grade), along with multiple episodes of vomiting, incompletely responsive to medications [16]. It was when the patient started refusing water, with inability to swallow (Hydrophobia: Pathognomonic of Rabies), that the patient was referred to NICD, New Delhi, suspecting Rabies Encephalitis [17].

Upon leading with questions further, the husband also gave a vague history of the patient exhibiting intolerance to light (Photophobia) while driving from hospital to hospital in his car, resistance to air on switching on the ceiling fan or opened windows while moving the car (Aerophobia) and inability to produce proper phonation (aphonia) preceding the current comatose state of patient’s presentation, all presenting since 11th day post-bite [18]. The restlessness, irritability progressed immediately, with the patient not slept at all for past 3-4 days before her presentation to our hospital.

Post her admission in our hospital, the patient was duly investigated. All her blood and serum investigations were non-significant except Renal function test, CSF examination and Magnetic resonance imaging of Brain [19]. Her renal function test was deranged with Urea = 88.0, Creatinine = 2.2 with reduced and dark coloured urine output (about 300-400ml per 24 hours), but with no alteration in Kidney echotexture / morphology (as examined on ultrasonography) [20]. The CSF fluid was clear, colourless with RBS = 74mg/dl, Proteins = 130mg/dl, TLC = 120 cells with 90% lymphocyte predominance in cellularity. The MRI Brain showed features of encephalitis, probably of viral aetiology [21].

The patient was then palliatively managed conservatively with antimicrobial agents (Acyclovir, Ceftriaxone) with an emphasis on hydration [22]. Keeping the most probable diagnosis as-‘Acute Rabies Viral Encephalitis’, palliative approach to manage the patient’s vitals and preventing her condition from further deterioration was primarily aimed, since most viral illnesses are self-limiting within 1-2 weeks [23].

Falling blood pressure was managed by adequate hydration, with monitoring of urine output, and regular blood sampling for renal function follow-up [24]. Any bradycardia was improved by Atropine on SOS basis. Regular suctioning using laryngoscope, nebulization and chest physiotherapy was done to maintain any respiratory inadequacy, with a mechanical ventilator kept on stand-by [25]. Limb physiotherapy, TPN (Total Parenteral Nutrition) was added for a generalised appreciable response. Maintained mostly in propped -up position, regular visits by her husband, brother , relatives were encouraged to boost her morale, as patient’s positive will was also primarily paid heed to once her sensorium started improving [26].

Miraculously , by Day 7 post-admission (Day 23 post-bite) , the patient responded positively with eye opening on touch ,followed by gradual improvement to spontaneous eye opening, with interspersed periods of varying conscious levels (lucid intervals) ,over the next 6 days [27]. On Day 13, the patient started showing signs of further improvement by accepting oral sips, and on day 20 (post-admission), the patient was shifted to ward. She was now able to interpret verbal commands and respond by speech, but in bi-syllables. Nasogastric tube feeds were initiated, along with TPN (Total Parenteral Nutrition) [28]. The patient was typically aimed at being managed, by stabilizing through the periods of vital impairments and agitation, using sedatives and other counter drugs [29].

The patient underwent physiotherapy and speech therapy, until Day 33 (post admission) / Day 51 (post bite), when the patient showed the ability of independent voluntary movements, and was discharged with prominent dysarthria, quadriparesis of improving prognosis.12 months post-discharge, the patient was followed up on out-patient basis, persistent with a mild neurological sequelae of wide stepped gait and myalgia, but was independent enough to perform her household chores [30].

Hence, we confirm that the patient had outlived the acute phase of neurological system inflammation, with a mild physical residua [31].

Discussion

Most of the present day knowledge about rabies has evolved from in vitro studies using fixed (attenuated) laboratory strains, and thus cannot be accurately matched with highly non-specific features, in clinical settings [24].

How to diagnose rabies?

For a laboratory disease confirmation, WHO recommends brain tissue biopsy demonstrating virus antigen as 100% sensitive gold standard technique, but this technique is preferred in post mortem diagnosis. The antemortem diagnostic tests, are limited, and highly influenced by intermittent virus shedding, timing of sample collection, type of sample, and the type of rabies, reflecting the peculiar pathogenesis of the virus lacking a viraemic phase and evading exposure to the systemic immune responses [24], with the standard being the Fluorescent antibody test demonstrating the presence of viral antigen.

Is rabies treatable?

Though no aggressive management was required in this case, the non-specific spectrum of the classic rabies survival cases, had no patterned management technique, other than conservatively treating the patient until the proposed theory of hyperactive immune response (natural or artificial) with high antibody levels in CSF and serum, successfully led to viral clearance [24]. Table 1 provides a brief detailed list of rare documented rabies survivors worldwide, till date.

CASE NO.   YEAR   AGE/SEX   PLACE MANNER OF INFECTION IMMUNIZATION STATUS TYPE OF RABIES DEVELOP AFTER CONFIRMED BY MANAGED BY RECOVERY IN SEQUALAE
  1. 1970 6yrs/M    USA Bite on left thumb, by a Bat Completed 14 Day course of Duck embryo rabies vaccine Paralytic 20 days of bite RABV isolated from the bat Intensive care, Aggressively,
Intubated
6 months    NONE5
  2. 1972 45yrs/F Argentina Severe Dog bite  Delayed 14 daily doses of suckling mouse brain vaccine & 2 booster doses Paralytic 21 days of bite Rabies neutralizing antibodies in serum, CSF Conservative management 13 months     MILD6
 
3.
1977 32yrs/M  USA Laboratory
exposure
  Duck embryo vaccine pre-immunized Paralytic 2 weeks Info not provided Intensive care, supportive 5 months    SEVERE7
  4.   1994 9yrs /M MEXICO Multiple dog bites on face 4 doses Vero vaccine & 2 doses human diploid cell culture vaccine Paralytic 19 days of bite Peak serum & CSF rabies neutralizing antibody titre Intensive care, on ventilator 3 weeks,
(Died after 3 years)
SEVERE8
  5. 2002 6yrs/F INDIA Dog multiple bites on hand, face 3 doses Purified chick embryo vaccine Furious 20 days of bite Rabies neutralizing antibodies in serum, CSF Conservative
With steroids
6 months SEVERE9
  6. 2004 15yrs/F  USA Bat bite on left index finger No vaccination Paralytic 1 month Rabies neutralizing antibodies in serum, CSF Milwaukee protocol 5 months  
MILD10
  7. 2007  
5 yrs /M
 Equitorial
Guinea
Dog bite on neck No vaccination Furious 5 weeks PCR positive saliva, FAT positive skin biopsy Milwaukee
protocol
20 days   DEATH 11
( due to malnutrition)
  8. 2008 15yrs/M BRAZIL Vampire bat bite 4-day delayed , 4 doses of vaccine taken Paralytic 6 days PCR positive skin biopsy Milwaukee protocol 1 month   MILD12
9. 2008 17yrs/M TURKEY Forearm and shoulder bite by dog 1 dose of Verorab ,given 4 days later Furious 21 days RT-PCR in CSF,Saliva, FAT corneal smear-positive Supportive, in isolation. 66 days NONE13
  10. 2009 17yrs/F USA Cave Bats exposure No vaccination Abortive 2months Rabies neutralizing antibodies in serum, CSF Conservative management (on outpatient basis)  15 days   NONE14
11. 2011 8yrs/F USA Multiple Cat scratch history No vaccination Paralytic 2months Rabies neutralizing antibodies in serum, CSF  
Intensive care, with Intubation
2 months NONE15
  12. 2011 13 yrs/F INDIA Dog bite, (Grade III) on leg. No vaccination Furious 2 years Rabies neutralizing antibodies in serum Supportive ,
In-patient care
Not specified NONE16
  13.  
2011
6yrs/M INDIA Grade III dog bite, on neck,back 3 doses chick embryo vaccine given *Atypical 22 days Rabies neutralizing antibodies in serum, CSF Supportive treatment 1 month SEVERE17
14. 2011 17yrs/M  INDIA Stray dog bite on left calf 4 late doses of purified chick embryo vaccine  Furious  22 days Rabies neutralizing antibodies in serum, CSF Intensive care & supportive 3 months SEVERE18
15. 2012 4yrs/M SOUTH AFRICA Dog bite on left ankle (grade III) late 3 doses PEP given  Furious 23 days Rabies neutralizing antibodies in serum, CSF Intensive supportive care 3 months SEVERE19
(Bedridden)
16. 2013 25yrs/M  
CHILE
Multiple dog bites on leg 1 dose of PEP vaccine given Paralytic/ non-specific 3 weeks (21 days) Rabies neutralizing antibodies in serum, CSF Milwaukee protocol with ventilation 4 months MILD20
  17. 2014 16yrs/M INDIA Stray dog bite 4 doses of PEP given Paralytic 1month RT-PCR from nuchal skin- Positive Intensive care with ventilator 3 months SEVERE21
(pituitary cachexia)
18. 2014 13Yrs/M INDIA   Dog bite 3 doses of Rabipur given *Atypical 1 month RT-PCR from nuchal skin,corneal smear- Positive Intensive Aggressive support care 6  Months  
SEVERE22
19. 2015 13yrs/F  INDIA Unknown / unaware No vaccination Furious 20 days RT-PCR,FAT for Rabies viral RNA,from CSF,nuchal skin-Positive Intensive care, with Milwaukee protocol 1 month NONE32
  20. 2016 36yrs/M GHANA Dog bite Right leg No vaccination Furious 10 days FAT on dog brain tissue- Positive Intensive care with sedation 23 days NONE23
  21. 2017 33yrs/F
(The Current Article)
INDIA Wild Badger, on the leg 4 doses of Pep taken Furious 18 days CLINICALLY Intensive supportive care 1 month MILD
22. 2017 14yrs/M BRAZIL several
Bat bite
episodes
No vaccination *Atypical Non-specific (multiple episodes  Other victim’s brain biopsy bitten by same bat   Milwaukee protocol 2months MILD28
  23. 2018 8yrs/M INDIA Dog bite on right hand 4 doses of Pep taken *Atypical 20 days Rabies neutralizing antibodies in serum, CSF, viral antigen Intensive care with ventilator 3 months SEVERE29
  24. 2018 11yrs/M INDIA Dog bite on right hand (grade III) 5 doses of Pep taken Paralytic 1 month Rabies neutralizing antibodies in serum, CSF Intensive care with ventilator 1.5 months SEVERE30
25. 2019 4yrs/M INDIA Dog bite (grade III) 3 doses of Pep taken Paralytic 2 weeks Rabies neutralizing antibodies in CSF Supportive treatment 1 month SEVERE31

Conclusions

With the references taken from the study of 25 (including current case) survivors, in an otherwise 100% fatal rabies encephalitis in humans, the maximum number of cases have been reported from the Indian continent, which directly corresponds to the endemicity in the region. Most of the survivors observed to be of the younger age group, and also the survivors noted to be presenting with high titres of antirabies virus antibody, it showcases the potential of a healthy immune competent body, with a pressing importance of passive immunization, to counteract the disease. With 16 out of 25 survivors presenting in the non-furious type, a trend of survival has thus been seen in the nonaggressive form of rabies, thus also stating the role of virulence and strain of the virus, in prognosis. Clinical manifestation of the disease was faster with the bite closer to head and neck, though no significant variation in the recovery process. As in diagnosing, confirmatory antemortem tests from the laboratory need to be readily upgraded with recent most techniques and availability for prompt intervention and treatment, with RT-PCR climbing up the charts in reliability.

The 2009 case of Texas, USA, is the first case reported of Abortive type, where recovery from rabies without any conservative or intensive care was noted 19. 6 out of 25 survivors have been tried management using Milwaukee protocol, and though not much of a beneficial track record for the same has been reported earlier, it seems to have a marginal incidental benefit in survival of the patient, and proposed to be promoted in its usage as an additional support therapy to conservative management.

With most cases , recovering within the span of 2-3 months of conservative intensive management, 3-4 cases have extended for up to 6 months and only one case took 13 months of hospital stay, before discharge, suggesting the time span of aggressive approach required to wade through to survive, for a symptomatic case. As most of the cases, have had remnants of neurological disability, 7 out of 22 cases have ended with Complete neurological recovery with no or mild neurological sequalae. Hence, it is not only important to clear the virus from CNS but also to ameliorate the neuronal injury caused by the viral infection. Therefore, a combination of antiviral therapy, immunotherapy and neuro-protective therapy, should be an important area of research in animal models, to contribute in establishing an effective treatment and therapy of human rabies.

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Citation: Sumirini, Acharya A, Manchanda BV, Mehra S (2022) The Rare Case of a Human Rabies Survivor & the Comparative Study of All Documented Human Rabies Survivors Till 2021. J Neuroinfect Dis 13: 257. DOI: 10.4172/2314-7326.1000372

Copyright: © 2022 Sumirini, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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