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Year : 2002  |  Volume : 20  |  Issue : 1  |  Page : 16-18

SSPE - The continuing challenge: A study based on serological evidence from a teritary care centre in India

Department of Clinical Virology, Christian Medical College and Hospital, Vellore - 632 004, India

Correspondence Address:
Department of Clinical Virology, Christian Medical College and Hospital, Vellore - 632 004, India

 ~ Abstract 

PURPOSE: To assess the prevalence of subacute sclerosing panencephalitis (SSPE). METHODS: In the period June 96 to December' 98 an analysis for measles virus (MV) antibody was carried out on 103 serum-CSF pairs received from patients clinically suspected of SSPE. Measles antibody was detected in an indirect immunofluorescent assay (IIF) test. RESULTS: Antibody to measles was detectable in 49 (48%) of the serum-CSF pairs tested, a diagnostic criterion for SSPE. Antibody titers ranged from 20 to 1280 in serum and neat to 32 in CSF. The serum: CSF ratio ranged from 5:1 to 80:1. Of the 49 patients diagnosed to have SSPE, 36 were males and 13 females, and the age of the patients at the time of diagnosis of SSPE ranged from 5 to 26 years. Ten of the SSPE patients gave a history of measles vaccination. CONCLUSIONS: Inadequate vaccine coverage and quality of vaccine used continue to have an impact on occurrence of SSPE.

How to cite this article:
Manayani D J, Abraham M, Gnanamuthu C, Solomon T, Alexander M, Sridharan G. SSPE - The continuing challenge: A study based on serological evidence from a teritary care centre in India. Indian J Med Microbiol 2002;20:16-8

How to cite this URL:
Manayani D J, Abraham M, Gnanamuthu C, Solomon T, Alexander M, Sridharan G. SSPE - The continuing challenge: A study based on serological evidence from a teritary care centre in India. Indian J Med Microbiol [serial online] 2002 [cited 2021 Mar 5];20:16-8. Available from:

Measles is an acute febrile exanthematous condition that is usually a self-limiting disease, but it can be associated with several complications one of which is subacute sclerosing panencephalitis (SSPE).[1],[2] It is thought to be due to the persistence of defective MV in the brain.[3] The exact pathogenic mechanism of SSPE remains unclear.[4] SSPE can be diagnosed by its clinical presentation that is characteristic, periodic EEG complexes, and elevated measles antibody titers in serum and cerebrospinal fluid (CSF).[5] SSPE is on the decline after the introduction of vaccination in developed countries like United States.[6] In developing countries like India SSPE continues to occur presumably due to late introduction of vaccination in 19867 or quality of vaccine used. Serological studies have reported a high annual incidence (21 cases per million population) of SSPE in India.[7] Molecular and epidemiological studies have shown that outbreaks of measles can occur even in countries that have already implemented vaccination programme due to introduction of variants of measles virus.[8] This may also have an impact on the occurrence of SSPE cases. Indirect immunofluorescence test (IIF) is a simple and sensitive method for detection of measles antibody.[9],[10] The present report is that of a hospital-based study to asses the prevalence of SSPE confirmed by the demonstration of MV antibody in serum and spinal fluid by IIF.

 ~ Material and Methods Top

Samples obtained during the period June 1996 to December 1998 comprised of 103 serum - CSF pairs received from patients either suspected of SSPE or to rule out its possibility. Eighty nine of the above 103 specimens were collected from patients attending clinics of Christian Medical College Hospital, Vellore while 14 of them were external samples referred from hospitals elsewhere in Tamil Nadu. Serum and CSF were collected simultaneously and stored at + 40C and were tested within three days of collection. The IIF test was carried out using Edmonston strain infected Vero cells as substrate.[10] Serial dilutions of the serum tested were from 1/10 through 1/80 and for CSF neat through 1/8, whenever there were no end point further dilutions were tested. Uninfected Vero cells were used as the negative control. Reciprocal of the highest dilution of serum and CSF showing a 2+ or more intense cytoplasmic fluorescence with unstained punched out nuclei were taken as the titer.[10] Serum: CSF ratio was calculated for all the samples. The records of all the patients who attended the clinics in Christian Medical College Hospital, Vellore were reviewed to correlate serological findings with their EEG patterns and the final diagnoses. Records were also reviewed to document measles vaccination status and a history of primary measles infection in childhood.

 ~ Results Top

During the 2.5 years period from June 1996 to December 1998, a final clinical diagnosis of SSPE was confirmed by serological evidence in 49 (48 %) of the serum-CSF pairs of 103 patients tested. Seven of the 49 positives were from patients attending hospitals elsewhere in the country. Serum antibody titers ranged from 40-1280 and neat to 32 in CSF. The serum: CSF ratio's ranged from 5:1 to 40:1 in 46 (94%) of 49 patients, only 3 patients had a serum: CSF ratio of 80:1. Thirty six (73%) of the 49 SSPE patients were males and 13 (27%) were females. The age and sex distribution of SSPE patients is shown in the [figure] (excluding one female patient whose age was not known). The patients principally came from the states of West Bengal, Bihar and Tamil Nadu. The mean age of the patients diagnosed to have SSPE was 13 years. The youngest age at which SSPE diagnosed was five years and the oldest was 26 years. We reviewed the charts of 42 serologically confirmed SSPE patients, excluding the external samples. Seventeen (40%) had a history of symptomatic primary measles infection in childhood and three had history of probable measles infection. Ten (24%) of the SSPE patients gave a history of measles vaccination. Thirty five (83%) of the 42 SSPE patients had an EEG pattern typical of SSPE correlating with the serological findings, in five patients EEG was not suggestive of SSPE and in the remaining two patients EEG was not done.

 ~ Discussion Top

This study shows that incidence of SSPE continues to be high, like a previous study published from Christian Medical College Hospital, Vellore.[7] In the previous study 81 serologically confirmed cases were documented in a period from 1983-87.[7] SSPE has occurred even after the introduction of vaccination in India in 1986 in children under 15 years of age. The mean age at which SSPE was diagnosed in our patient group was 13 years. A greater proportion of the SSPE patients were males.[11] Fifteen (36%) of the SSPE patients did not have any symptomatic primary measles infection. These individuals would have had a subclinical infection that is known to occur in India.[7],[12] The IIF test was sensitive enough to detect intrathecal antibody production in all SSPE patients a diagnostic criterion for SSPE. EEG findings in these patients typical of SSPE were more or less compatible with serological evidence. In this period maximum number of the SSPE patients fell within the age range of 5-19 years. It should be noted that ten of the patients gave a history of measles vaccination. The cases of SSPE in vaccinated individuals could have occurred due to poor seroconversion or vaccine failure, as there are no reported cases of vaccine associated SSPE. This could be either due to poor quality of vaccine (improper cold chain) or administration of measles vaccine at an earlier than the recommended age of 12-15 months or may be due to variants of measles virus.[13] For further reasoning as to why SSPE continues to occur, we may have to do molecular epidemiological surveys to get a clear picture of MV genotypes circulating in our country. This is because of introduction of heterogeneous genotypes from other countries resulting in measles outbreaks even in countries, which have successfully introduced vaccination.[14] An issue that needs to be addressed is whether geographical region specific vaccines have to be designed which will confer better immunity even to regionally prevalent genotypes. 

 ~ References Top

1.Ray CG. In: Harrison's Principles of Internal Medicine, Vol.1, 13th ed. Isselbacher KJ, Martin JB, Braunwald E, Wilson JD, Fauci AS, Kasper D Eds. (Newyork, USA: McGraw-Hill Inc) 1994: 825-827.  Back to cited text no. 1    
2.Modlin JF, Halsey NA, Eddins DL, Conrad JL, Jabbour JT, Chien L, et al. Epidemiology of subacute sclerosing panencephalitis. J Pediatr 1979; 94: 231-236.  Back to cited text no. 2    
3.Vardas E, Leary PM, Yeats J, Badrodein W, Kreis S. Case report and molecular analysis of subacute sclerosing panencephalits in a south african child. J Clin Microbiol 1999; 37: 775-777.  Back to cited text no. 3    
4.Oxman MN. In: Clinical Virology. Richman DD, Whitley RJ, Hayden FG Eds. (New York, USA, Churchill Livingstone) 1997: 821-861.  Back to cited text no. 4    
5.Khwaja GA, Gupta M, Sharma DK. Subacute sclerosing panencephalitis. J of Assoc of Phys of India 1991; 39: 928-933.  Back to cited text no. 5    
6.Hinman AR, Orenstein W A, Bloch A B, Bart K J, EddinsD L, Amler R W, et al. Impact of measles in the United States. Rev Infect Dis 1983; 5: 439-444.   Back to cited text no. 6    
7.Saha V, John TJ, Mukundan P, Gnanamuthu C, Prabhakar S, Arjundas G, et al. High incidence of subacute sclerosing panencephalitis in South India. Epidemiol Infect 1990; 104: 151-156.  Back to cited text no. 7    
8.Kreis S, Schoub BD. Partial amplification of measles nucleocapsid gene from stored sera and cerebrospinal fluids for molecular epidemiological studies. J Med Virol 1998; 56: 174-177.  Back to cited text no. 8    
9.Fulton RE, Middleton PJ. Immunofluorescence in diagnosis of measles infection in children. J Pediatr 1975; 86: 17-22.  Back to cited text no. 9  [PUBMED]  
10.John TJ, Ponnuraj EM, Mukundan P, Sridharan G. Indian J Med Microbiol 1996; 14: 183-186.   Back to cited text no. 10    
11.Carman WF, Johnson S. Subacute sclerosing panencephalitis in South Africa. Trans R Soc Trop Med Hyg 1989; 83: 117-118.  Back to cited text no. 11    
12.Cherian T, Joseph A, John TJ. Low antibody response in infants with measles and children with subclinical measles virus infection. J Trop Med Hyg 1984; 87: 27-31.   Back to cited text no. 12  [PUBMED]  
13.Katayama Y, Shibahara K, Kohama T, Homma M, Hotta H. Molecular epidemiology and changing distribution of genotypes of measles virus field strains in Japan. J Clin Microbiol 1997; 35: 2651-2653.  Back to cited text no. 13    
14.Bellini WJ, Rota PA. Genetic diversity of wild-type measles virus: implications for global measles elimination programmes. Emerg Infect Dis 1998; 4: 29-35.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
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