The Epidemic History of Hepatitis C Among Injecting Drug Users in Flanders, Belgium

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FULL TEXT: http://www.medscape.com/viewarticle/579268?src=mp & spon=3 & uac=31238BR

From Journal of Viral Hepatitis

The Epidemic History of Hepatitis C Among Injecting Drug Users in Flanders,

Belgium

Posted 09/05/2008

C. Matheï; S. Van Dooren; P. Lemey; P. Van Damme; F. Buntinx; A.-M. Vandamme

Abstract

Summary: We employed recently developed statistical methods to explore the

epidemic behaviour of hepatitis C subtype 1a and subtype 3a among injecting drug

users (IDUs) in Flanders, Belgium, using new gene sequence data sampled among

two geographically distinct populations of IDUs. First the extent of hepatitis C

transmission across regions/countries was studied through calculation of

association indices. It was shown that viral exchange had occurred between both

populations in Flanders as well as across international borders. Furthermore,

evidence was found suggestive of subtypes 1a and 3a predominantly circulating in

subpopulations of Flemish IDUs, exhibiting different degrees of

travelling/migration behaviour. Secondly, through coalescent-based analysis the

viral epidemic history of the hepatitis C subtype 1a and 3a epidemics was

inferred. Evidence was found for different dynamic forces driving both

epidemics. Moreover, results suggested that the hepatitis C subtype 3a epidemic

has reached a steady state, while the hepatitis C 1a epidemic has not, which

therefore might become the predominant subtype among IDUs.

Introduction

Soon after the discovery of the hepatitis C virus (HCV) in 1989, preventive

measures have been implemented to prevent HCV transmission.[1] These measures

have been proven very effective except with respect to the epidemic among

injecting drug users (IDUs).[2,3] Hepatitis C continues to spread rapidly among

IDUs.[4-8] Preventive measures such as information, education, needle-exchange

programmes, etc. have been proven to be successful in containing the human

immunodeficiency virus (HIV) epidemic among IDUs; however, they seem quite

ineffective for HCV, at most slowing the epidemic.[9-18]

A good understanding of the dynamics of the HCV epidemic is the cornerstone for

the development of an effective prevention policy. The rate of spread of HCV is

often derived from seroprevalence data collected over time course of the

epidemic. Such data are difficult to obtain and to interpret for the HCV

epidemic for a number of reasons. First, the beginning of the epidemic pre-dated

the discovery of the virus and there is lack of archived specimens enabling

retrospective seroprevalence measurements. Secondly, because hepatitis C is

seldom diagnosed during the acute stage, studies often have to estimate the date

of infection based on assumptions regarding risk factors or exposures.[19] It is

customary to estimate the date of infection with hepatitis C for IDUs in the

year that he/she started to inject. However, it has been shown that this

assumption is not correct for about 50% of the cases.[20] Thirdly, infection

with HCV does not confer to life-long immunity. Recent studies have showed that

re-infection with HCV after spontaneous clearance of the virus and sur-infection

are quite common events among IDUs.[21-23] Therefore seroprevalence data can be

considered as a measure for seroconversion but they underestimate the incidence

or the rate of spread of HCV among IDUs.

Several recent studies have demonstrated how coalescent theory can be used to

infer the past epidemic growth of HCV infection.[24-27] A fundamental result of

coalescent theory is the finding of a relationship between coalescent time and

population size. For any two sequences drawn from a population, the probability

that they coalesce at a given point in history is a function of population size.

Thus, a change in population size over time will leave a signature in the

patterns of RNA substitutions among HCV strains sampled within a population that

will depend on the direction (growth or decline) and tempo of this change. The

coalescent method estimates the history of changing viral population size using

phylogenetic trees that are reconstructed from randomly sampled viral gene

sequences. The change in the estimated number of HCV infections over time can

then be used to infer the growth rate and the basic reproductive number (R0).

The latter is defined as the number of secondary infections caused by an

infectious person in an entirely susceptible population.

In previous studies it has been shown that HCV exchange of European IDU

populations has occurred on a large scale, although regional differences were

observed, with for example strains from London being the most phylogenetically

dispersed.[28,29] The phenomenon of international travelling and international

contacts between IDUs should be kept in mind when developing prevention

programmes.

In the present study new sequence data were obtained from two geographically

distinct populations of IDUs in Flanders, Belgium. These data were used to infer

the epidemic and migration history of HCV subtypes 1a and 3a among IDUs in

Flanders, Belgium. First, the degree of transmission of HCV among IDUs between

two regions in Flanders and across international borders was investigated.

Secondly, the epidemic history of HCV among IDUs in Flanders was estimated.