EVALUATION OF EPIDEMIOLOGICAL FACTORS OF MEASLES INFECTION AND SEQUENCE ANALYSIS OF A LOCAL ISOLATE OF THE VIRUS IN NIGERIA
Abstract
Nigerian isolates of measles virus (MVNG) and its nucleotide sequence have not been compared with those of measles virus (MV) isolates from various parts of the world. This study therefore compared the neutralization capabilities and nucleotide sequence of MVNG with measles virus isolates (MVs) from other parts of the world and the investigation of some epidemiological parameters that constitute risk factors of measles infection in Nigeria. MVNG was isolated from blood sample of a measles patient using B95-a cell - line. The isolates was characterised and compared with various MVs from Gambia (West African), Luxembourg, Italy, and Belgium (Europe) and Taiwan (Asia). A structural protein MV- Heamaglutinin (MV-H) bearing the neutralizing epitopes of the virus was studied to detect differences in various isolates from different parts of the world for better understanding of the immunology and epidemiology of measles infection. The six isolates were also tested using a panel of monoclonal antibodies specific to predetermined epitopes of the MV-H to identify variations in the gene. Sera samples were obtained from subjects that recovered from measles more than forty years ago with no previous record of measles vaccination. In addition sera were obtained from acute measles patients and vaccines from Nigeria Europe and Asia. The neutralization indices of the serum samples on the six MV isolates were determined and compared. Reverse transcriptase polymerase chain reaction and nucleotide sequence analysis of the MV-H of the global isolates were compared phylogenetically with 15 representative sequences from the seven known lineage groups of the MVs using the CLUSTAL W signet program. The sera samples from Europe showed significant differences (p<0. 05-0.02) in their neutralization indices of MV from West Africa and Asia Significant differences (p<0.05) were also obtained in the neutralization of sera from donors without previous vaccination record to the MV currently circulating in Europe. This suggests antigenic drift in the strain of the virus with which these category of donors were infected before the introduction of measles vaccines and the currently circulating MVs. No significant changes (p>0.05) were observed in the neutralization profiles of sera from vaccine to the six isolates suggesting that the vaccines used globally are antigenically stable. The results of the neutralization tests with monoclonal antibodies were similar to those with polyclonal sera confirming the similarity of conformational epitome of various MVs. The nucleotide sequences of Nigerian and Gambian isolates were identical and more closely related to the Edmonton wild type strain of measles virus than the Asia Isolate. However, the European isolates were more divergent. The MVNG was found to belong to a lineage group different from all other known isolates.This study has provided more information on epidemiological factors of measles infection in Nigeria. The high characteristic morbidity and mortality of measles in Nigeria is associated with overcrowding, poor accommodation, and social facilities.
This study elucidated and compared the nucleotide sequence of the H-gene of a Nigeria isolate of the virus with isolates from other parts of the world.
Description
A Thesis submitted to the Faculty of Basic Medical Sciences in partial fulfillment of the requirements for the award of the Degree of Doctor of Philosophy in Virology, University of Ibadan.