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 ~  Abstract
 ~  Introduction
 ~  Case Report
 ~  Discussion
 ~  Acknowledgement
 ~  References
 ~  Article Figures

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  Table of Contents  
Year : 2011  |  Volume : 29  |  Issue : 2  |  Page : 178-180

Fatal rabies despite post-exposure prophylaxis

Department of Microbiology, Government Medical College, Panchakki Road, Aurangabad - 431 001, Maharashtra, India

Date of Submission13-Feb-2010
Date of Acceptance23-Mar-2011
Date of Web Publication2-Jun-2011

Correspondence Address:
D G Deshmukh
Department of Microbiology, Government Medical College, Panchakki Road, Aurangabad - 431 001, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.81786

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 ~ Abstract 

Only sporadic reports of failure of post-exposure prophylaxis for rabies exist in the published literature. We are reporting such a case in a 3-year-old boy. The child had Category III dog bite on his right thigh. He presented with progressive ascending paralysis, finally developing quadriplegia and respiratory paralysis. Typical hydrophobia and aerophobia were absent. He received four doses of antirabies cell culture vaccine. He did not receive antirabies immunoglobulin. The boy succumbed on the 23 rd day of the dog bite. Diagnosis of rabies was confirmed in the laboratory by demonstration of Negri bodies, direct fluorescent antibody test and reverse transcriptase-polymerase chain reaction either on impression smear of brain or a piece of brain taken during autopsy.

Keywords: Post-exposure prophylaxis, rabies

How to cite this article:
Deshmukh D G, Damle A S, Bajaj J K, Bhakre J B, Patil N S. Fatal rabies despite post-exposure prophylaxis. Indian J Med Microbiol 2011;29:178-80

How to cite this URL:
Deshmukh D G, Damle A S, Bajaj J K, Bhakre J B, Patil N S. Fatal rabies despite post-exposure prophylaxis. Indian J Med Microbiol [serial online] 2011 [cited 2021 Jan 19];29:178-80. Available from:

 ~ Introduction Top

Rabies is a major public health problem in developing countries. [1] The Indian subcontinent accounts for almost half of the deaths worldwide due to rabies encephalitis. [2] Virtually all is known in order to eliminate this scourge by controlling the disease in the canine population and by providing post-exposure prophylactic treatment recommended by the World Health Organization (WHO). Nevertheless, true post-exposure prophylactic failures do occur, although rarely. The most common are those due to deviations from WHO Management Recommendations and lack of quality biological. [1],[2]

Here, we report a fatal case of rabies despite the use of purified chick embryo cell vaccine.

 ~ Case Report Top

A 3-year-old child had dog bite on right thigh on 6 th January 2009. There was a single bite mark in the form of lacerated wound of size 2 cm × 2.5 cm (category III). The dog was a stray dog of the same locality and had symptoms of rabies. It was killed by people on the next day. The child received four doses of purified chick embryo cell-derived antirabies vaccine (Rabipure; Chiron Behring Vaccines Pvt. Ltd. Mumbai India) on 7 th , 12 th , 17 th and 20 th January, 2009. The next dose of vaccine was due on 5 th February 2009. He did not receive antirabies serum. The child remained asymptomatic till 24 th January, 2009. On 25 th January, 2009, he developed fever, pain and weakness over the right lower limb. On the same day, he was referred to our tertiary care hospital.

On admission, the patient was febrile and drowsy and vital signs were stable. There was no sign of neck rigidity, no cerebral signs and the ophthalmic examination was within normal limits.

Cerebrospinal fluid (CSF) examination revealed slightly increased protein, 110 mg% (normal range, 15-45 mg%). CSF sugar was 80 mg%, which was within the normal range.

The weakness initially involving the right lower limb progressed to involve the left lower limb, followed by the upper limbs over the next 2 days. Finally, he developed quadriplegia. However, the classical symptoms of rabies, i.e. hydrophobia and aerophobia, were not present any time during his illness.

On 27 th January, 2009 the patient developed respiratory paralysis. The patient was intubated and cardiopulmonary resuscitation was given. However, the patient died at 2 am on 28 th January, 2009. Provisional diagnosis of rabies encephalitis was made even though classical symptoms of rabies, such as aerophobia and hydrophobia, were not present. The possibility of vaccine-induced acute disseminated encephalomyelitis, although rare with the modern cell culture vaccine, was also considered. To confirm the diagnosis, an autopsy was performed giving more attention to the brain.

On gross examination, the brain was mildly congested. Eight impression smears from the hippocampus of the brain were taken and four were stained with Sellers stain. [3] Intracytoplasmic inclusion bodies indicative of Negri bodies were detected by microscopic examination [Figure 1]. Half of the brain was collected in 50% glycerol-saline for further confirmation. Direct immunofluorecence test was performed on the remaining impression smears. Reverse transcriptase polymerase chain reaction was performed on the collected brain tissue, which confirmed the diagnosis of rabies.
Figure 1: Impression smear from the hippocampus of the brain showing intracytoplasmic acidophilic inclusion body in the neuron (x1000)

Click here to view

 ~ Discussion Top

There are two forms of human rabies: the encephalitic furious form and the paralytic dumb form. [4] The encephalitic form, seen in about 80% of the cases, starts with fever, malaise, pharyngitis and paraesthesia at the site of the bite followed by the classical neurological symptoms of hydrophobia, aerophobia, agitation, hypersalivation and seizures. This is followed by paralysis and coma. Death is usually due to respiratory failure.

Paralytic rabies accounts for approximately 20% of the cases of rabies; hydrophobia and aerophobia are present in only half of these patients. It closely resembles the Guillion Barre Syndrome.

In the present case, hydrophobia and aerophobia were absent. In one study, [5] 5% of the rabies cases did not have hydrophobia. [6] An earlier study [6] reported that 24.4% of the patients had neurological symptoms but no hydrophobia.

Although an estimated 10 million people receive post-exposure prophylaxis (PEP) each year after being exposed to rabies suspect animal bites, only sporadic reports of failure of PEP exist. [1],[2],[4],[7] Wilde [1] has reviewed 15 cases of probable or possible failure of rabies PEP. The various reasons quoted by him for such failure include:

  1. Rabies immunoglobulin (RIG) not used at all, injected only intramuscularly and not into wounds or not all bite wounds injected.
  2. Vaccine or RIG of poor quality.
  3. An exceptionally large viral load was introduced.
  4. Virus injected directly into a nerve.
  5. Unrecognized or unreported deviations from the WHO PEP protocol.
One of the studies [2] have attributed the failure to short incubation period, failure to infiltrate maximum human rabies immunoglobulin (HRIG) locally and suturing of wound. Lack of administration of RIG in spite of WHO Category III exposure was the reason in another report,[4] whereas one more report says that they have followed all WHO guidelines for rabies PEP and the cause of failure is thought to be direct inoculation of the virus into nerve endings. [7]

The present case appears to be rabies PEP failure. In the present case, the child belonged to a poor farmer family and was living in a remote village. In rural India, some misconceptions are prevalent. One such misconception is that if water touches a wound it leads to sepsis. Therefore, the wounds are not washed. Considering the social background, it seems unlikely that the dog bite wound of this patient was washed immediately. The dog being rabid (as deduced from the description provided by the parents) and the type of the wound, it is likely that a large viral load was introduced at the time of bite.

He was brought to the Government District Hospital the next day. On this day, he was administered the first dose (the 0 dose) of Rabipur. Thereafter, the parents were asked to bring the child for the remaining doses on days 3, 7, 14 and 28 as prescribed by the WHO. The parents of the child are illiterate and poor. Transportation facilities from their village to the district place are also inadequate. Hence, the child was brought on days 5, 11 and 14, leading to mild deviation from the recommended schedule. However, more important is the fact that RIG was not administered, although recommended by the WHO for all category III dog bite wounds. After going into the details as to why it was not given, the reason put forth was non-availability of both equine RIG and HRIG in the Government District Hospital. As already mentioned, the parents being poor could not afford these.

Thus, at least two of the guidelines regarding PEP of rabies, viz. washing the wound and use of immunoglobulin to treat category III dog bite wound, have been disregarded in the present case.

It is necessary to increase the general cleanliness and hygiene concepts among the rural folk in India. It is well documented that up to one-third of rabies infections can be prevented by careful wound cleansing and disinfection, which costs virtually nothing compared with the rest of PEP procedures and biological. [8],[9]

Similarly, health care providers must be better educated regarding wound care and PEP. We also need to continue our efforts to make the tools for PEP (quality vaccines and immunoglobulins) more widely available.

To summarize, classical signs of rabies like hydrophobia and aerophobia may not be present in every case. Proper care of the wound, use of proper dosage and schedule of rabies vaccine and use of RIG as recommended by the WHO should be followed.

 ~ Acknowledgement Top

We would like to acknowledge Dr. VN Srinivasan, Research Director, Indian Immunological Limited, Hyderabad, India, for his further confirmation of the case "By reverse transcription - polymerase chain reaction and direct fluorescent antibody test."

 ~ References Top

1.Wilde H, Sirikawin S, Sabcharoen A, Kingnate D, Tantawichien T, Harischandra PA, et al. Failure of post-exposure treatment of rabies in children. Clin Infect Dis 1996;22:228-32.  Back to cited text no. 1
2.John BM, Patnaik SK. Fatal rabies despite appropriate post- exposure prophylaxis. Indian Pediatr 2005;42:839-40.  Back to cited text no. 2
3.Joseph JM. Cytologic and cytochemical techniques for study of viral infections. In: Sonnenwirth AC, Jurett L, editors. Gradwohl's clinical laboratory methods and diagnosis, 8th ed. Vol. 2. St. Louis: The C. V. Mosby Company; 1980.p. 2052-3.   Back to cited text no. 3
4.Mohite A, Prasad V, Rajam L, Madhusudana SN. Rabies encephalitis. Indian Pediatr 2005;42:702-4.  Back to cited text no. 4
5.Chhabra M, Ichhpujani RL, Tewari KN, Lal S. Human rabies in Delhi. Indian J Pediatr 2004;71:217-20.  Back to cited text no. 5
6.Krishna K, Dutta JK. Human rabies in Delhi (1976). Indian J Public Health 1978;22:259-64.  Back to cited text no. 6
7.Hemachudha T, Mitrabhakdi E, Wilde H, Vejabhuti A, Siripataravanit S, Kingnate D. Additional reports of failure to respond to treatment after rabies exposure in Thailand. Clin Infect Dis 1999;28:143-4.  Back to cited text no. 7
8.Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of rabies infected wounds. Bull WHO 1963;28:477-86.  Back to cited text no. 8
9.World Health Organization. Recommendations on rabies postexposure treatment and the correct technique of intradermal immunization against rabies. EMC. ZOO96.6. Geneva (Switzerland): WHO; 1996  Back to cited text no. 9


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