Acute flaccid paralysis due to rabies.

TWO CLINICAL FORMS OF RABIES ARE RECOGNIZE: i) a furious form associated with classical signs of excitation or phobic symptoms, ii) Dumb rabies (paralytic rabies) characterized by progressive paralysis without an initial furious phase wherein distinction from Guillain-Barré Syndrome may be difficult. Paralytic rabies is more common in persons who have received postexposure vaccination. We report here the diagnostic dilemma of two cases of acute flaccid paralysis due to rabies.

Introduction

The diagnosis of rabies is not very difficult when associated with the classical features of excitations or phobias (aerophobia, hydrophobia). But it can be quite challenging when presented as acute flaccid paralysis (AFP). Paralytic rabies is more common in persons who have received postexposure vaccination.[12] We report here two cases of paralytic rabies who received four doses of postexposure (grade III dog bite) vaccination without rabies immunoglobulin. Paralytic rabies occurring after postexposure antirabies vaccination creates a diagnostic dilemma as vaccine-induced GBS becomes a distinct possibility.

Case Reports

Case 1

A ten year-old boy presented with sudden weakness of both lower limbs for two days. He also had a history of fever, vomiting, and back pain for three days. His past history elicited an incident of an unprovoked bite by a street dog in his right hand (grade III) three weeks back. Four doses of purified chick embryo cell (PCEC) antirabies vaccine were administered according to schedule in the deltoid, starting from the day of the bite.

Rabies immunoglobulin (RIG) was not given. The patient had complained of back pain, but there was no typical history of pain, tingling, numbness at the site of the bite, hydrophobia, or behavioral changes. Clinical examination revealed a febrile, alert, and conscious child. His temperature was 39.5°C, pulse rate was 110/min, blood pressure 100/70 mm Hg, respiratory rate 30/min, and SPO2 96%. Neurological examination detected grossly reduced muscle tone and power (lower limb 2/5, upper limb 3/5) with areflexia (both superficial and deep tendon reflexes were absent) in all four limbs and the trunk along with urinary incontinence. There were no features of sensory or cranial nerve involvement. The failure to administer RIG after the grade III bite favored a provisional diagnosis of paralytic rabies was made even though the classical symptoms of rabies were absent. Although rare with the modern cell culture vaccines, the possibility of vaccine-induced GBS was also considered.

Laboratory investigations showed hemoglobin: 11.5 g/dL, white cell count: 70000/cu.mm (neutrophil: 58%, lymphocyte: 40%, eosinophil: 2%), platelet count: 1,90000/cu.mm. Cerebrospinal fluid analysis showed cell count: 10/cu.mm (all lymphocytes), protein: 50 mg/dL, and sugar: 80 mg/dL (no albumino-cytological dissociation). Microorganisms were not detected either by gram stain or by culture. The electrophysiological test designed to identify features of demyelination (slowing of nerve conduction velocity with marked prolongation of distal latencies and occasional conduction block), was inconclusive. Serum electrolytes were normal—Na: 136 meq/L, K: 5 meq/L. Liver function, renal function tests, and repeat CSF examination on the 7th day were unremarkable. A serological test for rabies was not possible due to some technical difficulties. .

Conservative management was started but rapid progression of paralysis occurred over the next two days. There was involvement of respiratory muscles as well as features of bulbar palsy. The patient was put on ventilatory support. Intravenous immunoglobulin (2 g/kg/total dose) was given over 12 hours for the sake of caution, but there was no improvement and the patient succumbed on the 10th day of onset of the disease.

Due to inadequate stool collection by the AFP surveillance worker, all the documents were sent to the National Expert Committee (National Polio Surveillance Project) as a special case.[3] They classified the case as being nonpolio and as paralytic rabies.

Case 2

A six year-old girl presented with sudden onset of quadriparesis for one day, preceded by fever, myalgia, and vomiting for four days. There was also a history of a dog bite in her right upper arm (Grade III bite) three weeks back.

The child was given the PCEC vaccine as per schedule in the deltoid and received a total of four doses before the development of any symptoms. In that case also RIG was not given though it was indicated. The patient was treated conservatively, but the clinical features and the progression of disease was similar to the first case, except for the presence of myoedema, a striking feature of rabies.[14] In spite of good supportive measures, she expired on the 12th day of disease onset.

Results of laboratory investigations on the 11th day of the illness were also quite similar to the first case. The CSF test was strongly positive for rabies antigen and immune complexes. Neutralizing antibodies to rabies virus were detected in both serum and CSF by the Rapid Fluorescent Focus Inhibition Test (RFFIT).

Discussion

There are two forms of human rabies: i) the well-known encephalitic (furious) and ii) the paralytic (dumb) rabies. The encephalitic form 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. The second clinical form of rabies, paralytic (dumb) or Guillain-Barré-like, is characterized by progressive paralysis without an initial furious phase. Even though the paralytic rabies is unfamiliar to health care providers, 20–30% of rabies victims present in this manner.[1]

Paralytic rabies is more common after rabid vampire bat bites and in persons who have received postexposure vaccination.[2] Distinction of paralytic rabies from GBS may be difficult, although individuals with GBS usually do not have urinary incontinence, which is common in rabies.[4] In our two cases, fever at the onset of disease, the absence of albumin-cytological dissociation, even repeat CSF examination and persistent urinary incontinence was against the diagnosis of vaccine-induced GBS.

Different sites of neural involvement and possibly different neuropathogenetic mechanisms may explain the clinical diversity in human rabies. The pathological basis of paralysis in paralytic rabies is not well understood. It is unclear whether weakness results from the involvement of anterior horn cells or of motor nerve fibers. Most likely, peripheral nerve dysfunction, due to demyelination, contributes to the weakness seen in paralytic rabies. On the other hand, progressive focal denervation starting at the bitten segment, was evident in furious rabies, even in the absence of demonstrable weakness. The electrophysiological study suggested anterior horn cell dysfunction. Intense inflammation of the spinal nerve roots was observed to a greater extent in paralytic rabies patients. Inflammation was mainly noted in the spinal cord segment corresponding to the bite in all cases. However, central chromatolysis of the anterior horn cells could be demonstrated only in furious rabies patient. In both patients, NCV findings revealed features of demyelination which may occur in paralytic rabies as well as in GBS.

Studies conducted in the US by the Center for Disease Control and Prevention (CDC) have documented that a regimen of one dose of RIG and five doses of the human diploid cell culture vaccine (HDCV) over a period of 28 days was safe and induced an excellent antibody response in all recipients.[5] Clinical trials with Rabies Vaccine Adsorbed (RVA) and Purified Chick Embryo Cell (PCEC) vaccine have also demonstrated immunogenicity equivalent to that of HDCV.[6] Occasional failure has been reported with cell culture vaccines due to incorrect administration. Many individuals did not receive immunoglobulin where indicated and some of them received the vaccine in the gluteal region instead of in the deltoid.[7] Although both of our patients had grade III dog bite for which RIG is strongly recommended, they only received the vaccine in the deltoid region without RIG. This was most probably the cause of vaccine failure.

Neurological reactions following newer vaccine administration have been extremely rare. After millions of vaccinations worldwide, three Guillain-Barré type paralytic reactions have been described, and all cases recovered completely.[8] If our patients had vaccine-induced GBS, definitely they were improved by good supportive measures.

During the early stages of paralytic rabies, notable signs include myoedema, particularly in the region of the chest, deltoid muscles, and thighs.[1] However, this phenomenon, a brief, unpropagated, localized muscle contraction that appears in response to percussion with a tendon hammer, is not a confirmatory sign of paralytic rabies but was present in our 2nd case.

If there is an inadequate stool sample with residual paralysis, death of the patient, or loss to follow-up at the time of AFP surveillance, the case is referred to the National Expert Committee (National Polio Surveillance Project) review for final classification as nonpolio AFP or compatible with poliomyelitis.[3] In our first case, there was inadequate stool sampling, so it was reviewed by the expert committee and declared to be paralytic rabies.