Measles in Sudan: Diagnosis, Epidemiology and Humoral Immune Response

Despite the availability of safe and effective live attenuated vaccines, measles remains endemic in many developing countries. Little is known about the pathogenesis of measles virus (MV) infections in the areas of itsendemicity, largely due to the limited infrastructure and political instability. Whereas measles in industrialised countries is often considered an “innocent” childhood disease, measles case-fatality rates are often well above 1% in developing countries, and can be even higher in outbreak situations (5). Oneexplanation for this observation is that measles is associated with a transient immunosuppression resulting in an increased susceptibility to other infectious agents: the infectious pressure of many human pathogens is substantially higher in developing countries than in the industrialised world. Incombination with vitamin deficiencies (e.g. vitamin A) and inadequate case management this increases the risk of MV infection developing into a serious life-threatening disease (3). However, prior to or co-infections with otherpathogens could also play a role in modifying the specific immune responseto MV infection. In particular the high prevalence of parasitic infections inmany developing countries could affect the development of the cellular immune system towards a dominance of T-helper (Th) cells producing type 2 cytokines such as IL-4, IL-5 IL-10 and IL-13. Such responses have beenassociated with immunosuppression (197), and counterbalance Th responsesproducing type 1 cytokines (such as IL-12 and interferon-γ) which sustaincytotoxic T cell (CTL) response and have been associated with clearance ofMV infection (198). Towards the control and eventual eradication of measles more insight will be required in the pathogenesis of measles in areas of its endemicity. However, another reason to study measles in these regions is that it allows the development and validation of alterna

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

Combination of reverse transcriptase PCR analysis and immunoglobulin M detection on filter paper blood samples allows diagnostic and epidemiological studies of measles.

As measles control and elimination campaigns progress, laboratory confirmation of clinically diagnosed measles cases becomes increasingly important. However, in many tropical countries collection and storage of clinical specimens for this purpose are logistically complicated. In this study it is shown that blood samples spotted on filter paper are suitable for the laboratory diagnosis of measles using a combination of reverse transcriptase PCR (RT-PCR) analysis and immunoglobulin M (IgM) detection. First, it was shown that in vitro measles virus (MV)-infected cells diluted in human blood and spotted on filter paper can be detected by RT-PCR. Small amounts of infected cells remained detectable after 25 weeks of storage of the filter paper at room temperature, 4 weeks at 37 degrees C, or 2 weeks at 45 degrees C. Subsequently, this RT-PCR was applied to filter paper blood samples collected from 117 clinically diagnosed measles patients in Sudan in 1997 and 1998. Prior laboratory diagnosis had confirmed 90 cases as acute MV infections, while 27 proved to be nonmeasles rash disease cases. Positive RT-PCR signals were detected in filter paper bloo