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Promotion of oral fluid methods for evaluation and surveillance of the measles immunization programme in Ethiopia

By Wondatir Nigatu


This work aims to demonstrate the use of oral-fluid methods in evaluating the effectiveness of a vaccination programme at the individual (vaccine conversion) and population levels (herd immunity and virus transmission and origin) within a developing country context. The setting for this work was Ethiopia- a country beset with huge economic, social and logistical difficulties in vaccine programme implementation. The study comprises the following: First, the development and evaluation of highly sensitive measles specific IgG/IgM ELISAs using oral-fluid, second, the application of these assays to evaluate routine and campaign measles vaccination programmes, and third genotyping of measles virus strains circulating in the country, again using oral-fluid samples.\ud Paired blood and oral fluid samples were obtained from787 individuals of all ages from rural Ethiopia for evaluation of the measles enhanced IgG antibody capture (GAC) enzyme linked immunosorbent assay (ELISA). Relative to serum, oral fluid assay sensitivity and specificity were: 97.4% and 91.1% for measles IgG. This work is the development and evaluation of a new method that has contributed scientifically to vaccination programme evaluation and refinement.\ud Pre- and post-vaccine antibody determined in 296 children attending for routine measles immunization in Addis Ababa suggested the average vaccination age at which 92.6% (200/216) seroconversion rate attained was about nine and half months. Oral-fluid based testing show 87.3% (185/212) seroconversion rate for IgM antibody compared to the 92.6% serconversion rate for serum. This work included the development and use of an oral-fluid enhanced MACELISA as a useful substitute to serum in evaluating vaccine seroconversion.\ud RT-PCR was performed for oral-fluid and serum samples collected from outbreaks and sporadic measles cases across the country to study the molecular genotype characteristics of the strains. Sequence analysis of outbreaks and sporadic case samples revealed that the viruses of the D4, D8 and B3 genotypes were found in the country. This study also demonstrates the practicality of integrating oral-fluid based genotyping into measles surveillance efforts.\ud Pre-campaign survey work carried out in Assella town by collecting oral-fluid samples from 1928 children aged 9-59 months visiting vaccination stations, and post-campaign survey work undertaken by cluster-based random sampling of 750 oral fluid samples from eligible individuals aged between 9 months to <20 years clearly show (i) a shortfall in measles 'immunity 'in the target age group (9-59 months), and (ii) a significant deficit in 'immunity' in those too old to have received the vaccine. This work demonstrates for the first time the merit of oral-fluid sampling in evaluating a measles vaccine campaign.\ud The main achievements summarized above, give weight towards the practicality of using oral fluid in evaluating and refining immunization programmes in the developing country setting. It waits to be seen if the non-invasive technology will gain wider support in the measles control activities

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  1. (1998). A comparison of oral fluid and serum for the detection of rubella-specific antibodies in a community study in Addis Ababa, Ethiopia. Trop Med Int Health
  2. (2001). A comparison of oral fluid collection devices for use in the surveillance of virus diseases in children. Public Health
  3. (1995). A comparison of the nucleotide sequences of measles virus L genes derived from wildtype viruses and SSPE brain tissue. Virology
  4. (1993). A nested case-referent study of under-five mortality and its public health determinants. Bull WHO
  5. (2000). A plan to reduce measles deaths. Nature Medicine
  6. (1996). A school outbreak of parvovirus B19 infection investigated using salivary antibodies assays. Epidemiol Infect
  7. (1998). A sensitive method of detecting proteins on dot blot and western blots using a monoclonal antibody to FITC. J Imrnunol Methods
  8. (1997). A simplified and standardized neutralization enzyme immunoassay for the quantification of measles neutralizing antibody.
  9. (1979). A solid-phase RIA for the detection of IgM antibodies to hepatitis A virus.
  10. (1990). Accurate assays for anti-HIV in urine. Lancet
  11. (1997). An evaluation of nine Commercial EIA Kits for the detection of measles specific IgG. J Virol Methods
  12. An evaluation of oral fluid collection devices for the determination of rubella antibody 205 status in a rural Ethiopian community. Trans Roy Soc Trop Med Hyg 1998b; 9:
  13. (1998). and sex-specific HIV-1 prevalence in the urban community setting of Addis Ababa,
  14. (1989). Antigenicity of the measles virus haemagglutinin studied by using synthetic peptides.
  15. (2001). Authority (CSA). Federal Democratic Republic of Ethiopia. Statistical Abstract,
  16. (1992). Baculovirus expression of the nucleoprotein genes of measles virus and utility of the recombinant protein in diagnostic enzyme immunoassays.
  17. (1994). Central statistical Authority (CSA). Federal Democratic Republic of Ethiopia. The
  18. (1998). Characterization of a new genotype of measles virus detected in China and England. Epidemiol Infec
  19. (1997). Child immunization in Ghana: the effect of family, location, and social disparity.
  20. (1996). Comparative detection of measles-specific IgM in oral fluid and serum from children by an antibody-capture IgM EIA.
  21. (1995). Comparison of commercial enzyme immunoassay kits with plaque reduction neutralization test for detection of measles virus antibody.
  22. (1990). Comparison of two assays (EIA and EITB) and two samples (saliva and serum) for the diagnosis of neurocysticercosis. Trans R Soc Trop Med Hyg
  23. (1997). Detection of IgG antibody to Epstein-Barr virus viral capsid antigen in saliva by antibody captures radioimmunoassay.
  24. (1995). Detection of IgM antibodies specific for measles virus capture and indirect enzyme immunoassays. Res Virol
  25. (1983). Detection of IgM antibodies to measles virus by enzymei mmunoassay. Med Microbiol Immunol
  26. (1999). Detection of measles specific IgG in oral fluid using an FITC/anti-FITC IgG capture enzyme-linked immonosorbent assay (GACELISA). J Virol Methods
  27. (1995). Detection of measles virus genome directly from clinical samples by 204 reverse transcriptase-polymerase chain reaction and genetic variability. Virus Research
  28. (1990). Detection of measles virus genomic sequences in SSPE brain tissue by the polymerase chain reaction. JMed Virol
  29. (1993). Detection of measles, mumps and rubella antibodies in saliva using capture radioimmunoassay.
  30. (1999). Detection of rubella virusspecific immunoglobulin G in saliva by an amplification-based enzyme-linked immunossorbent assay using monoclonal antibody to fluorescein isothiocynate.
  31. (1992). Detection of salivary antibodies in cats infected with feline immunodefieciency virus.
  32. (1994). Determination of measles, mumps and rubella status using oral fluid samples. JAmer Med Ass
  33. (1996). Development of a dual target-PCR for detection and characterization of measles virus in clinical specimens. Mol Cell Prob
  34. (1989). Diagnosis of hepatitis A and B by testing saliva.
  35. (1995). Diagnosis of measles virus.
  36. (1992). Disease Control and Prevention, Vaccination coverage of 2-year-old children-United States,
  37. (1999). Disease Control and Prevention.
  38. (1990). Effect of monovalent measles and trivalent measles-mumps-rubella vaccines at various ages and concurrent administration with hepatitis B vaccine. Pediatr Infec Dis J
  39. (1962). Enders JF. Measles virus: historical review, isolation and behavior in various systems.
  40. (1997). Epidemiological Record
  41. (1992). Epidemiological surveillance for health research and intervention in primary health care.
  42. (1998). Evaluation of haemagglutinin protein-specific immunoglobulin M for diagnosis of measles by an enzyme-linked immunosorbent assay based on recombinant protein produced in highefficiency mammalian expression system.
  43. (1991). Evaluation of monoclonal antibody-based capture enzyme immunoassays for detection of specific antibodies to measles virus.
  44. (1998). Exanthem subitum (roseola infantum) in infants misdiagnosed as measles and rubella. BMJ
  45. Expanded program on Immunization, Global Advisory Group. Revised plan of action for global measles control. WHO working paper no.
  46. (1997). Expanded programme on immunization progress towards global measles control and elimination. Weekly Epidemiological Report
  47. (1999). Expanded programme on immunization- standardization of the nomenclature for describing the genetic characteristics of wild-type measles viruses (update). Weekly Epidemiological Report
  48. (1994). Expanded Programme on Immunization, Global Advisory Group-Part II. Achieving the major disease control goals. Weekly Epidemiological Record
  49. (1985). Expanded Programme on Immunization, Global Advisory Group. Weekly Epidemiological Record
  50. (1994). Expanded Programme on Immunization. Accelerated measles strategies (summary of report of the GPV/CVI Informal Consultation on strategies to accelerate global measles control.
  51. (1979). Expanded programme on immunization. Measles immunization. Weekly Epidemiological Record
  52. (1989). Expression of measles virus nucleoprotein in Escherichia coli: use of deletion mutants to locate the antigenic sites.
  53. (2001). Fr. Has oral fluid the potential to replace serum for the evaluation of population immunity levels? A study of measles, rubella and hepatitis B in rural Ethiopia. Bull WHO
  54. (1990). Further-attenuated measles vaccine: virus passages affect viral surface protein expression, immunogenicity and histopathology pattern in vivo. Res Virol
  55. (1997). Future applications of oral fluid specimen technology.
  56. (1998). Genetic and antigenic characterization of the haemagglutinin protein of measles virus strains recently circulating in the UK. Virus Res
  57. (1997). Genetic characterization of wild-type measles viruses circulating in suburban Khartoum,
  58. (1992). Genetic variability of the glycoprotein genes of current wild-type measles isolates. Virology
  59. (1999). Genotypic and antigenic characterization of haemagglutinin proteins of African measles virus isolates. Virus Research
  60. (1986). Geographical variation in infant loss of maternal antibody and in prevalence of rubella antibody.
  61. (1962). Growth of measles virus in KB cells. Virology
  62. (1989). Guerin et at. Serological effects of Edmonston-Zagreb, Schwarz, and AIK-C measles vaccine strains given at ages 4-5 or 8-10 months. Lancet
  63. (1998). Guide to the 1998 Ethiopia National Immunization Days', Addis Ababa,
  64. (1981). Guidelines for EPI in Ethiopia, Addis Ababa.
  65. (1991). Hepatitis C virus RNA in saliva of patients with post-transfusion hepatitis C infection. Lancet
  66. (1991). Identification of several different lineages of measles virus.
  67. (1999). IgM antibodies in hospitalized children with febrile illness during an inter-epidemic period of measles, in Somalia.
  68. Immunogenicity and safety of measles vaccine in ill African Children.
  69. (1978). Immunologic recovery after measles. Clin Exp Immunol
  70. (1984). Inadequate immunity to measles in children vaccinated at an early age: effect of revaccination. Bull WHO
  71. (1993). Infection of monocytes during measles.
  72. (1991). Infectious Diseases of Humans. Dynamics and Control,
  73. (1978). Infectious Diseases,
  74. (1978). Infectious Diseases: Prevention and Treatment in the Nineteenth and Twentieth Centuries.
  75. (1959). Isolation and identification of measles virus.
  76. (1994). Laboratory diagnosis of measles infection and monitoring of measles immunization. Memorandum from a WHO meeting.
  77. (1986). Long-term antibody response after measles vaccination in an isolated arctic society Greenland. Vaccine
  78. (1990). Marmoset lymphoblastoid cells as a sensitive host for isolation of measles virus.
  79. (1982). Measles and SSPE viruses: similarities and differences. Prog Med Virol
  80. (1998). Measles antibody levels in vaccinated population in Brazil. Trans Roy Soc Trop Med Hyg
  81. (1990). Measles antibody: Reevaluation of protective titers.
  82. (1962). Measles as a universal disease. Am JDis Child
  83. (1985). Measles control: so near and yet so far. '
  84. (1996). Measles elimination in the Americas: evolving strategies.
  85. (1999). Measles elimination: progress and challenges. Vaccine
  86. (1984). Measles encephalomyelitis: lack of evidence of viral invasion of the central nervous system and quantitative study of the nature of demyelination.
  87. (1988). Measles eradication experience in the Americas. Bull WHO
  88. (1977). Measles immunity in the first year after birth and optimal age of vaccination in Kenyan children. Collaborative study by the MOH-Kenya and WHO. Bull WHO
  89. (1990). Measles immunization strategies for countries with high transmission rates: interim guidelines predicting using a mathematical model.
  90. (1987). Measles immunization: success and failures.
  91. (1982). Measles in England and Wales I. Analysis of factors underlying seasonal patterns.
  92. (1983). Measles mortality and vaccine efficacy in rural West Africa. Lancet
  93. (1979). Measles surveillance and control in Tunisia:
  94. (1995). Measles vaccination policy. Epidemiol Infect
  95. (1978). Measles vaccine efficiency in children previously vaccinated at 12 months of age. Pediatrics
  96. (1983). Measles vaccine in the People's Republic of China. Rev Infect Dis
  97. (1986). Measles virus haemagglutinin gene, cloning complete nucleotide sequence analysis and expression in COS cells.
  98. (1988). Measles virus L protein evidences elements of ancestral RNA polymerase. Virology
  99. (1985). Measles virus P gene codes for two proteins.
  100. (1995). Measles virus strain variations.
  101. (2002). Measles virus strains circulating in Central and West Africa: geographical distribution of two B3 genotypes.
  102. (2001). Measles virus strains circulating in Ethiopia in 1998/9: molecular characterisation using oral fluid samples and identification of a new genotype. JMed Virol
  103. (1957). Measles virus: a summary of experiments concerned with isolation, properties, and behavior.
  104. (1993). Measles: An Historical Geography of a Major Human Viral Disease: From Global Expansion to Local Retreat,
  105. (1985). Medical knowledge and urban planning in tropical Africa'. American Historical Review
  106. (1991). Model-based comparisons of measles immunization strategies using high dose Edmonston-Zagreb type vaccines.
  107. (1990). Molecular analysis of structural protein genes of the Yamagata-1 strain of defective subacute sclerosing panencephalitis virus. I. Nucleotide sequence of the nucleoprotein gene. Virus Genes
  108. (1996). Molecular epidemiology of measles virus: Identification of pathways of transmission and the implication for measles elimination.
  109. (1999). Molecular epidemiology of Nigerian and Ghanaian measles virus isolates reveals a genotyping circulating widely in western and central Africa.
  110. Molecular identification of two distinct haemagglutinin types of measles virus by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Mol Cell Probes1995;
  111. (1966). Multiplication of measles virus in cell cultures. Bact Rev
  112. (1979). New principles for the detection of specific IgM antibodies applied in an ELISA for hepatitis A. J Med Virol
  113. (2001). Nomenclature for describing the genetic characteristics of wild-type measles viruses (update). Weekly Epidemiological Report
  114. (1991). Non-invasive virological diagnosis: are saliva and urine specimen adequate substitutes for blood? Reviews in Medical Virology
  115. (1993). Novel assay for the detection of immunoglobulin G antihuman immunodeficiency virus in untreated saliva and urine. JMed Virol
  116. (1991). Nucleotide sequence of the genes encoding the matrix protein of the two wild-type measles virus strains.
  117. (1968). of the Twenty-first World Health Assembly.
  118. Office for Europe. HFA Statistical Database.
  119. (1973). Oligoclonal IgG antibody response in the central nervous system to different measles virus antigens in subacute sclerosing panencephalitis. Proc Natl Acad Sci USA
  120. (1998). Oral fluids as an alternative to serum for measurement of markers of immune activation. Clin Diag Lab Immunol
  121. (1999). Osterhaus ADME. Measles in a Dutch hospital introduced by an immunocompromised infant from Indonesia infected with a new virus genotype. Lancet
  122. (1977). Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure.
  123. (1993). Polymerase chain reaction for detection of measles virus in clinical samples.
  124. (1967). Practices Advisory Committee (USA). Measles vaccines. MMWR
  125. (1995). Prevalence of measles antibody among children under 15 years of age in Santa Cruz, Bolivia: implications for vaccination strategies. Trans Roy Soc Trop Med Hyg
  126. (1999). Progress towards global control and regional elimination 1998-1999. Weekly Epidemiological Record
  127. (1954). Propagation in tissue cultures of cytopathic agents from patients with measles. Proc Soc Exp Biol Med
  128. (1956). Propagation of measles virus in a strain of human epidermoid cancer cells (Hep-2). Proc Soc exp Biol Med
  129. (1956). Propagation of measles virus in human carcinoma cells.
  130. (1988). Recent rubella virus infection indicated by a low avidity of specific IgG.
  131. (1995). Report of a joint national review of the Expanded Programme on Immunisation (EPI), Ethiopia. Family Planning Department, Ministry of Health,
  132. (2000). Report of the annual African task force in Pretoria;
  133. (1998). Report of the work group on viral diseases.
  134. (1988). Restricted synthesis of the fusion protein of measles virus at elevated temperatures.
  135. (1988). Rubella-specific IgG subclass avidity ELISA and its role in the differentiation between primary rubella and rubella re-infection. Epidemiol Infect
  136. (1987). Saliva as a source of feline leukemia virus antigen for diagnosis of disease.
  137. (1974). Saliva in forensic odontology.
  138. (1995). Salivary antibody detection in epidemiological surveys: a pilot study after a mass vaccination campaign against rubella in Sao Paulo, Brazil. Trans Roy Soc Trop Med Hyg
  139. (1991). Salivary diagnosis of measles: a study of notified cases in the UK,
  140. (1998). Salivary diagnosis of rubella: a study of notified cases in the United Kingdom, 1991-4. Epidemiol Infect
  141. (1992). Salivary IgA antigliadin antibody as a marker for coeliac disease. Arch Dis Child
  142. (1987). Sensitive assays for viral antibodies in saliva: an alternative tests to serum. Lancet
  143. (1964). Separation of measles virus components by equilibrium centrifugation in CsCL2 gradients. I. Crude and Tween and ether treated concentrated tissue culture material. Arch Ges Virusforsch
  144. (1997). Sequence analysis of the nucleocapsid gene of measles virus isolates from South Africa identifies a new genotype.
  145. (1985). Sequence homology within morbilliviruses.
  146. (1986). Severe measles in the Gardulla area of South West Ethiopia. J Trop Paed
  147. (1998). Should measles be eradicated? BMJ
  148. (1998). Slopes of a receiver operating characteristics curve and likelihood ratios for diagnostic test.
  149. (1988). Specific immunoglobulin A to Bordetella pertussis antigensin mucosal secretion for rapid diagnosis of whooping cough.
  150. (1986). Specific immunoglobulin M enzyme linked immunosorbent assay for the confirming the diagnosis of measles.
  151. (2002). Stability of total and rubella-specific IgG in oral fluid samples: the effect of time and temperature.
  152. (1998). Statistical methods in medical research. 2nd Ed. Blackwell Scientific Publications,
  153. (1965). Studies on immunity to measles.
  154. (1958). Studies on measles virus monkey kidney tissue cultures. 2. Development of cytopathic changes and identification of the cultivated agents by complement fixation tests. Acta Path microbiol Scand
  155. (1991). Successful immunization of infants at 6 months of age with high dose Edmonston-Zagreb measles vaccine. Pediatr Infect Dis J
  156. (1997). Surveillance of measles in England and Wales: implication of a national saliva testing programme. Bull WHO
  157. (1995). Temporal and geographical distribution of measles virus genotypes.
  158. (1992). The diversity of measles virus in the UK,
  159. (1997). The epidemiology of rubella in England and Wales before and after the 1994 measles and rubella vaccination campaign: fourth joint report from the PHLS and the National Congenital Rubella Surveillance Programme. Communicable Disease Report CDR Review
  160. The immunological basis for immunization.
  161. (1986). The matrix genes of measles virus and canine distemper virus, cloning, nucleotide sequences deduced amino acid sequences.
  162. (1991). The molecular biology of the morbilliviruses. In: The Paramyxoviruses,
  163. The need for serologic evaluation of immunization programs.
  164. (1986). The nucleotide sequence of the mRNA encoding the fusion protein of measles virus (Edmonston strain): a comparison of fusion proteins from several different paramyxoviruses. Virology
  165. (1983). The optimal age for vaccination against measles in an Asiatic city, Taipei, Taiwan: reduction of vaccine induced titer by residual transplacental antibody.
  166. (1994). The pathogenic aspects of measles virus infection: memorandum from a WHO meeting. Bull WHO
  167. (1986). The predicted primary structure of measles virus haemagglutinin. Virology
  168. (1993). The testing of saliva samples for HIV-1 antibodies-reliability in a non-clinical setting. Genitourin Med
  169. (1991). The use of antibody avidity measurement for the diagnosis of rubella.
  170. (1997). The use of mass campaigns in the expanded program on immunization: A review of reported advantages and disadvantages.
  171. (1988). The use of saliva for viral diagnosis and screening. Epidemiol Infect
  172. (1988). Trial of high-dose Edmonston Zagreb measles vaccine in The Gambia: antibody response and side effects. Lancet
  173. (1984). Tropical and Geographic Medicine,
  174. (2000). UK measles outbreak in non-immune anthroposophic communities: the implication for elimination of measles from Europe. Epideriol Infect
  175. (1990). Use of mixture models in determining laboratory criterion for identification of seropositive individuals: application to parvovirus B19. J Virol Methods
  176. (1997). Vaccination in pulses: astrategy for global eradication of measles and polio? Trends in Microbiology
  177. World Eradication of Infectious Diseases.

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