BACKGROUND
In 1994 a small cluster of hepatitis-C cases in Rhesus-negative women in Ireland prompted a nationwide screening programme for hepatitis-C antibodies in all anti-D recipients. A total of 55 386 women presented for screening and a history of exposure to anti-D was sought from all those testing positive and a sample of those testing negative. The resulting data comprised 620 antibody-positive and 1708 antibody-negative women with known exposure history, and interest was focused on using these data to estimate the infectivity of anti-D in the period 1970-1993.
METHODS
Any exposure to anti-D provides an opportunity for infection, but the infection status at each exposure time is not observed. Instead, the available data from antibody testing only indicate whether at least one of the exposures resulted in infection. Using a simple Bernoulli model to describe the risk of infection in each year, the absence of information regarding which exposure(s) led to infection fits neatly into the framework of 'incomplete data'. Hence the expectation-maximization (EM) algorithm provides estimates of the infectiousness of anti-D in each of the 24 years studied.
RESULTS
The analysis highlighted the 1977 anti-D as a source of infection, a fact which was confirmed by laboratory investigation. Other suspect batches were also identified, helping to direct the efforts of laboratory investigators.
CONCLUSIONS
We have presented a method to estimate the risk of infection at each exposure time from multiple exposure data. The method can also be used to estimate transmission rates and the risk associated with different sources of infection in a range of infectious disease applications.
[1]
R. R. Hocking,et al.
Maximum Likelihood Estimation with Incomplete Multinomial Data
,
1971
.
[2]
D. Rubin,et al.
Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper
,
1977
.
[3]
C. Fuchs.
Maximum Likelihood Estimation and Model Selection in Contingency Tables with Missing Data
,
1982
.
[4]
M. Houghton,et al.
Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.
,
1989,
Science.
[5]
E. Holmes,et al.
Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region.
,
1993,
The Journal of general virology.
[6]
P. Yap,et al.
Hepatitis C viraemia in recipients of Irish intravenous anti-D immunoglobulin
,
1994,
The Lancet.
[7]
S. Frøland,et al.
Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin.
,
1994,
The New England journal of medicine.
[8]
P. Simmonds,et al.
Hepatitis C virus transmission by intravenous immunoglobulin.
,
1994,
Journal of hepatology.
[9]
C. Weinberg,et al.
Modeling conception as an aggregated Bernoulli outcome with latent variables via the EM algorithm.
,
1996,
Biometrics.