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Subacute sclerosing panencephalitis (SSPE) is a rare, chronic neurological disease of children and adolescents resulting from persistent measles virus (MV) infection of brain cells. SSPE generally develops 5 to 10 years after acute measles, starting with subtle signs of intellectual and psychological dysfunctions and continuing with sensory and motor function deterioration and progressive cerebral degeneration, leading to death after a period of months or years (14). Various mechanisms of this persistent MV infection of the brain have been suggested, including the presence of defective viral particles and alterations in viral gene expression, particularly hypermutations and deletions in some of the viral genes (11).

The significant epidemiological characteristics of SSPE cases in all the published South African papers to date are shown in Table 1. The reported incidence of SSPE in South Africa ranges from 2.6 cases/1,000,000 people per year in the earlier studies (7, 8), before the introduction of universal measles immunization, to 0.39 case/1,000,000 people per year in the later studies (2, 9). The most recent South African SSPE incidence figure of 0.43 case/1,000,000 people per year (3) is lower than the global estimate of 1 case/1,000,000 people per year (11). Furthermore, although the earlier South African SSPE studies showed a clear racial and geographical distribution of cases, with the highest prevalence of SSPE being found in children of mixed race from the Cape Province (7-9), subsequent studies show no racial differences in SSPE incidence. The rate of occurrence of SSPE disease in black children (0.39 case/1,000,000 people per year) is not significantly different from that in white children (0.63 case/1,000,000 people per year) (13). However, distinct clustering of SSPE cases within South Africa in the Cape Province, first noted between 1970 and 1975 (8), continues to be demonstrated. The Cape Province consistently shows a higher prevalence of SSPE cases than the rest of the country and the Southern African region (4, 7-9). Other epidemiological features of SSPE in South Africa include an almost equal male-to-female distribution of cases, with a male/female ratio of 0.9:1 (9), which is not consistent with the male predominance of SSPE found in studies from other countries (11). Also, most South African children demonstrate acute measles infection at an early age: at least 42% of SSPE patients have natural measles infection before the age of 1 year (4, 10), with a median age of 11.1 years at SSPE onset (13).

We describe here the clinical features and molecular characteristics of a single case of SSPE in a child from South Africa. To genotype the MV in this case, we amplified viral genomic material from the 3' terminus of the nucleocapsid (N) gene from both cerebrospinal fluid (CSF) and blood. This is the genomic region most commonly used to genotype MV in molecular epidemiological studies (2).

Informed consent was obtained from the parents of the subject. Clearance from the Committee for Research on Human Subjects and Ethics at the University of the Witwatersrand, Johannesburg, South Africa, has been obtained for this work, protocol M960201. Human experimentation guidelines as specified by this committee were followed in the conduct of the clinical research.

Case report. In March 1997 a black female child aged 4 years, 10 months, was referred for further investigation to the Red Cross Children's Hospital (Cape Town, South Africa) from Port Elizabeth (Eastern Cape Province, South Africa) after she had failed to respond to treatment for epilepsy, her initial diagnosis. According to her mother, the child had been well until January 1997, at which time she noticed that the child was "falling" while playing. These episodes increased in frequency and severity over the next 2 months, with the child falling to the ground after every few steps. There was no history of classical seizures or change in mental status. Also, there was no clear history of natural measles infection, and the mother thought the child had received all her childhood immunizations.

Further investigations of blood and CSF specimens. To explore the characteristics of the MV causing SSPE in this patient, viral RNA was extracted from both blood and CSF specimens and amplified by reverse transcriptase PCR by using a technique which has been described previously (5). MV-specific primers from two overlapping fragments of the 3' terminus of the N gene (375 and 384 bp, respectively) were used (6). Both serum and CSF yielded identical sequences of the 3' terminus of the MV N gene. There was no evidence of any hypermutations or deletions in this gene. Sequence analysis of the N gene placed the virus from this case into genotype D3, clade D (6).

Discussion. This is the first report of SSPE from South Africa with genetic characterization of the causative virus. The D3 viral genotype identified in this case has never been found in Africa before. Previously it has been shown that MVs from three genotypes (A, D2, and D4) have been circulating in South Africa since 1978, with genotype D4 representing the major genetic group (5). However, the virus associated with this case of SSPE clearly belonged to genotype D3, based on the N gene sequences identified. The last documented indigenous circulation of wild-type D3 MV occurred in the United States in 1992 (2). It is possible that the D3 genotype exists as a minor genotype in South Africa that has so far evaded the MV molecular epidemiological surveillance done in this country, as these studies have not directly examined the circulating viruses from the Eastern Cape, where this child lived. Alternatively, this child may have been exposed to the D3 virus through contact with an infected person who travelled to South Africa from another country. The pathway of transmission is impossible to establish at this stage.