Measles virus protein-specific IgM, IgA, and IgG subclass responses during the acute and convalescent phase of infection.

The availability of new generation serological assays allowed re-evaluation of the antibody response to measles virus. IgM, IgA, total IgG, and IgG subclass responses were studied to the three major immunogenic measles virus proteins: the fusion protein (F), haemagglutinin (H), and nucleoprotein (N). Plasma samples were obtained from clinically diagnosed measles cases (n = 146) in Khartoum (Sudan) within a week after onset of the rash. Convalescent phase samples were collected from 32 of 117 laboratory-confirmed measles cases at different time points after onset of rash. Glycoprotein-specific IgM, IgG, and IgA antibody levels correlated well to the N-specific response. For IgG and IgA, responses to F were higher than to H. IgA antibody levels were undetectable in about one third of the laboratory-confirmed cases during the acute phase, but positive in all patients tested 1-4 weeks after infection. IgM levels declined rapidly and were lost 3-6 months after infection. IgA levels declined slowly during the first year but did not return to background levels during the subsequent 2 years. IgG avidity maturation was detected during a 3-6 month period after infection. The predominant IgG subclasses during the acute phase were IgG(1) and IgG(3). The latter was lost in the convalescent phase, while the IgG(4) isotype showed a slight rise afterwards. Interestingly, acute phase IgG(3) and IgA responses were associated, and were only detected in samples with high IgG. This study provides a comprehensive perspective on the antibody response to wild-type measles virus infection.

Genetic characterization of wild-type measles viruses circulating in suburban Khartoum, 1997-2000.

Measles remains endemic in many East African countries, where it is often associated with high morbidity and mortality. We collected clinical specimens from Sudanese measles patients between July 1997 and July 2000. Sequencing of the 3' 456 nucleotides of the nucleoprotein gene from 33 measles virus (MV) isolates and 8 RNA samples extracted from clinical specimens demonstrated the presence of a single endemic MV strain with little sequence variation over time (overall nucleotide divergence of 0 to 1.3%). This was confirmed by sequencing of the complete H gene of two isolates from 1997 and two from 2000, in which the overall divergence ranged between 0 and 0.5%. Comparison with MV reference strains demonstrated that the viruses belonged to clade B, genotype B3, and were most closely related to a set of viruses recently isolated in Nigeria. Our study demonstrates a remarkable genetic stability of an endemically circulating MV strain.

Serological and virological characterization of clinically diagnosed cases of measles in suburban Khartoum.

Measles continues to be a major childhood disease in terms of global morbidity and mortality. In the main areas of its endemicity the only available means of diagnosis are based on clinical criteria: the presence of a maculopapular rash and fever accompanied by cough, coryza, and/or conjunctivitis. We have studied 38 clinically diagnosed cases of measles in Khartoum, Sudan, by means of serology, reverse transcriptase PCR (RT-PCR) on throat swabs and virus isolation from lymphocytes. On the basis of serology, 28 patients were diagnosed as having an acute measles virus (MV) infection, while in 10 cases the clinical symptoms proved to have other causes. It was shown that in cases with low serum immunoglobulin M (IgM) levels, an additional measurement of IgG or virus-neutralizing antibodies was necessary to discriminate between patients with an acute MV infection sampled during an early stage of the disease and patients who had experienced an MV infection in the more distant past. The serological laboratory diagnosis was validated by an MV-specific RT-PCR: for all confirmed measles cases tested a fragment of the correct size which hybridized with a third MV-specific primer could be amplified, while all serologically negative cases were also RT-PCR negative. MV could be isolated from 17 out of 23 of the serologically confirmed cases, demonstrating that virus isolation is less reliable as a diagnostic tool than serology or RT-PCR. This study stresses the urgent need for a rapid diagnostic field test for measles.