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

By Nokes, D. James; Enquselassie, Fikre et al. | Bulletin of the World Health Organization, July 2001 | Go to article overview

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


Nokes, D. James, Enquselassie, Fikre, Nigatu, Wondatir, Vyse, Andrew J., Cohen, Bernard J., Brown, David W. G., Cutts, Felicity T., Bulletin of the World Health Organization


Voir page 594 le resume en francais. En la pagina 594 figura un resumen en espanol.

Introduction

Community surveys of the prevalence of specific IgG antibodies have frequently been used to study the epidemiology and improve control of viral infections. For example, the proportion of individuals with specific IgG antibody, stratified by age, provides information on population immunity and susceptibility, rates of transmission, vaccine "take", and target ages and coverage for elimination (1-7). The need for such surveys is increasing worldwide, particularly for the evaluation and refinement of immunization programmes, e.g. measles elimination strategies (8) and rubella control programmes (9, 10). However, the full potential of antibody prevalence studies will not be realized, most especially in the developing world, as long as such studies depend on the collection of blood samples.

The use of samples of oral fluid as a non-invasive alternative to blood for the detection of virus-specific antibodies was first promoted in 1987 (11). Assays that are sensitive and specific for IgG antibodies to human immunodeficiency virus type 1 (HIV-1) in saliva and urine have subsequently been widely used for surveillance, and commercial assays for this purpose are now available. In comparison, development of oral-fluid IgG antibody detection assays for most other viral infections has been slow. Assays that reliably detect measles-, mumps-, and rubella-specific IgM in oral fluid are used for surveillance purposes in the United Kingdom (12, 13); however, it has proved difficult to develop oral-fluid-based measles- and rubella-specific IgG assays that are sensitive enough to replace serum assays.

The results of recent studies have, however, moved us closer to realizing the wider use of oral fluid in surveys of viral-specific IgG. For example, novel specific IgG enzyme-linked immunosorbent assays (ELISAs) based on antibody capture that are of adequate sensitivity and specificity to substitute for serum have been developed and evaluated for measles (14) and rubella (15).

Increased use of surveys of specific IgG antibody prevalence as a tool in immunization programme evaluation and epidemiological studies will depend on the demonstration of the utility of oral-fluid methods for this purpose. We report here the results of a study of the use of oral-fluid samples to determine IgG antibodies specific to measles, rubella, and hepatitis virus B core antigens in a rural community of southern Ethiopia. Attention focused on the utility of oral fluid in population prevalence estimation studies rather than on the diagnosis of infection at the level of the individual.

Materials and methods

Study population and survey design

The district of Butajira, where the study was carried out, lies 130 km SSW of Addis Ababa, capital of Ethiopia, and is flanked to the SE by the edge of the Rift Valley and to the NW by the Gurage mountains. The population of 250 000 consists largely of subsistence farmers, has high density, and is dispersed in villages located at 1500-2300 m altitude, with in addition a small town of 10 000 population. Administratively there are 82 villages or farmers' associations (FAs), and 4 urban dwellers' associations (UDAs) or kebeles in the town, each with a population of 2500-5000. Measles vaccination coverage is low in the district (study sample: village mean, 16.6%; and town mean, 54.8%) and there is no vaccination coverage against viral hepatitis B or rubella. Since 1986 the study site has formed the basis for a longitudinal demographic and health surveillance programme known as the Butajira Rural Health Project (BRHP) (16, 17). The BRHP study population comprises 37 000 inhabitants in 9 FAs and 1 kebele (10 clusters), with each cluster selected from the total administrative units with probability proportional to size.

We conducted a survey between May and November 1997 in which oral-fluid samples were collected from all consenting and available occupants (4631 of 5063 (91. …

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