Scholarly article on topic 'Partial recovery from rabies in a six-year-old girl'

Partial recovery from rabies in a six-year-old girl Academic research paper on "Clinical medicine"

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Academic research paper on topic "Partial recovery from rabies in a six-year-old girl"

Letter to the Editor

Partial recovery from rabies in a six-year-old girl

S.N. Madhusudana,(1) D. Nagaraj,i2) M. Uday,f2) E. Ratnavalli(2) and M. Verendra Kumar(2^ Int J Infect Dis 2002; 6: 85-86

Human rabies is still considered a 100% fatal disease though occasional reports of survival have been reported from time to time,1-2 including a recent report from South America.3 As recovery from rabies in animals is well documented,4 it is possible that mechanisms that operate in animals may also contribute to rare instances of recovery in human beings. This report describes a case that was treated at the National Institute of Mental Health and Neurosciences (NIMHANS) in the past year.

A six-year-old girl was admitted at the neurologic services of NIMHANS Bangalore, India, with a 4-day history of fever, inability to swallow liquids, photophobia and visual hallucinations, and altered sensorium for 2 days. She had been bitten on the face and hands 20 days previously by a street dog, which also bit other people in the locality. The dog died 4 days later. The child was given three doses of purified chick embryo cell vaccine (PCECV, Rabipur) on day 0, 3, and 7. No local wound treatment was given, and rabies immunoglobulin (RIG) was not administered. On examination the child was found to be semiconscious but obeyed simple commands. Neurologic examination revealed minimal weakness of both lower limbs with brisk tendon reflexes. Routine laboratory investigations were normal. Plain and contrast computed tomography (CT) at this stage did not reveal any abnormality. A strong possibility of rare neural complications to PCECV was considered, and the patient was started on methyl-prednisolone, antibiotics, and intravenous fluids and managed conservatively. To complete the course of postexposure treatment she was also administered one dose of human diploid cell vaccine (HDCV) on the second day of admission. There was no improvement in the child's condition, and she became comatose by the fourth day. There was excessive salivation and frothing at the mouth with profuse sweating. At this stage, she also developed focal motor seizures. Magnetic resonance imaging (MRI) revealed hyperintense signals in T2-weighted images in basal ganglia, brain stem, and

Departments of (1)Neurovirology and <2)Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

Address correspondence to Dr. S.N. Madhusudana, Associate Professor, Department of Neurovirology, National Institute of Mental Health and Neuroscience, PB No. 2900, Hosur Road, Bangalore 560029, India. E-mail: mshampur@hotmail.com.

Corresponding Editorial Office: New York

cerebral cortex, suggestive of encephalitis rather than post-vaccinal demyelination. A strong possibility of rabies encephalitis was considered at this stage, which was also supported by presence of unusually high titers of rabies antibodies in the child's serum and cerebrospinal fluid (CSF) samples with significant rise in titers with repeat samples. The rabies antibody titers (determined by mouse neutralization test as advocated by the World Health Organization (WHO)5 in serum and CSF on day 8 of illness were 1:64 and 1:8, respectively, and these rose to 1:512 and 1:512 by day 15 of illness, to 1:56,000 and 1:32,000 by day 22 of illness, and to a maximum of 1:265,000 and 1:124,000 on day 90 of illness (Table 1). As such high titers of antibodies are never reported after a course of any cell culture rabies vaccine, a strong possibility of rabies was considered. Direct immunofluorescence on frozen section skin biopsy from the nape of the neck was negative for rabies antigen and so was a corneal test. The CSF revealed pleocytosis, but virus could not be isolated by mouse inoculation or Neuro 2a cell inoculation. However, intrathecal synthesis of antibodies in the CSF was demonstrated on four separate occasions by the method of Tibling et al,6 supporting the diagnosis of rabies encephalitis (Table 1). The child remained comatose for 3 months while conservative management continued. The steroids were tapered and discontinued, and the patient gradually showed improvement in the level of sensorium in the next 2 months. By the end of the fifth month she was responding to simple commands and could feed orally. During this time she had developed rigidity of both upper and lower limbs and involuntary movements involving both limbs; frequent opisthotonoid postures were also noted from time to time.

Table 1. Rabies neutralizing antibody titers observed in serum and CSF

Titers in serum* Titers in CSF*

Day of Illness (lU/mL) (lU/mL)

8f 64(1.2) 8 (0.15)

15 512 (12) 512 (12)

22 56,000 (1,200) 32,000 (800)

29 120,000 (4,800) 96,000 (2,400)t

42 210,000 (5,040) 120,000 (2,880)t

90 265,000 (6,360) 124,000 (3,100)t

110 312,000 (7,800) 182,000(4,550)*

11 months 46,000 (1,140) 8,200 (196.8)

*Reciprocal of 50% endpoint dilution.Figures in parenthesis indicate titers in lU/mL.

tOne dose of human diploid cell vaccine given on this day. ^Intrathecal synthesis demonstrated.

86 International Journal of Infectious Diseases / Volume 6, Number 1,2002

After 6 months the patient was discharged with instructions for frequent follow-ups. The child was examined 3 times in the past year, and there was not much improvement in her condition. However, the rabies antibody titer had fallen in both serum and CSF and was 1:46,000 and 1:8,200 at the eleventh month of illness.

The child is reported to be still alive after 18 months from the day of her illness.

Rabies is endemic in India, and nearly 30,000 human deaths are reported every year.7 Dogs are the vectors of transmission in over 95% of cases.

Though human rabies is still considered a fatal disease, contradicting reports have come from time to time. Here, the case of a six-year-old girl developing encephalitis following dog bite and partial treatment with a cell culture rabies vaccine is reported. Two possible diagnoses were considered: neurologic complication following rabies vaccine or rabies encephalitis. Considering all the epidemiologic, clinical, radiologic and serologic findings, the authors believe that this is a possible case of recovery from rabies. The dog that bit her most likely was rabid, as it had shown symptoms of rabies, bit several people, and died within 4 days. Although the virus was not isolated and viral antigen was not demonstrated at any time during the illness, the authors believe that there is strong indirect evidence to support this diagnosis. The high titers of rabies antibodies in both serum and CSF with significant and sustained rise in titer and intrathecal synthesis cannot be accounted for by 4 doses of vaccine alone. Also, the child had no history of rabies vaccination or exposure to rabies. The MRI was indicative of encephalitis rather than post-vaccinal de-myelination. High titers of rabies

antibodies persisted in CSF even after 11 months of illness. The child has not recovered completely and presently has rigidity, tremors, and involuntary movements of limbs, which perhaps could be explained as a sequel to the encephalitic process. Such rare reports backed by well documented cases of recovery in animals should encourage physicians to institute rigorous intensive measures to prolong life in patients with rabies, with the hope that the virus may clear in due course with partial or complete recovery.

REFERENCES

1. Hattwick MA, Weis IT, Stechschulte CJ, Baer GM, Gregg MB. Recovery from rabies. A case report. Ann Intern Med 1972;76:931-942.

2. Porras C, Barboza JJ, Fuenzalida E, Adaros HL, Oviedo AM, Furst J. Recovery from rabies in man. Ann Intern Med 1976;85:44-48.

3. Alvarez L, Fajardo R, Lopez E, et al. Partial recovery from rabies in a nine-year-old boy. Pediatr Infect Dis J 1994; 13:1154-1155.

4. Fekadu M, Baer GM. Recovery from clinical rabies of two dogs inoculated with a rabies virus strain from Ethiopia. Am J Vet Res 1980; 41:1632-1634.

5. Atanasiu P. Quantitative assay and potency test of antirabies serum and immmunoglobulin. In: Kaplan MM, Koprowsky H, eds. The laboratory techniques in rabies. 3rd ed. Geneva: WHO, 1973:314-318.

6. Tibbling G, Link H, Ohman S. Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 1977; 37: 385-390.

7. Sehgal S. Medical and veterinary aspects of rabies prevention and control in India. Indian J Comm Health 1996;2: 18-19.