This survey revealed three major findings. First, there was a considerable period of parasite persistence in adults asymptomatically infected with E. histolytica. Second, the vast majority of carriers remained asymptomatic during the 15-month observation period. Third, the various E. histolytica genotypes were stable during the course of the infection.
The study was performed primarily to determine the dynamics of E. histolytica
infection in a population from a setting in which the parasite is endemic rather than to determine variables that may influence clinical outcomes. Previous studies have already shown that about 10% of the residents from Phu Cat, Hué, are infected with E. histolytica
but that the annual incidence of amebic liver abscess is only about 0.7% in adult males and considerably lower in children and adult females (3
). Thus, the single amebic liver abscess observed during the study was within the range of what was expected for a sample size of 383 individuals of which only 177 were males.
To our knowledge only two studies of the time course of intestinal E. histolytica
infection in untreated carriers have been reported (10
). These studies, conducted in areas of amebiasis endemicity in South Africa and Bangladesh, respectively, suggested a much faster clearance of the parasite and a considerably higher rate of reinfection. However, besides differences in geographic and local conditions, the individuals enrolled in the South African and Bangladeshi studies were considerably younger, comprising mainly children and young adults aged ≤20 years, whereas our study subjects from Vietnam were all >20 years old (mean age, 38.5 years). Whether children are able to clear E. histolytica
more rapidly remains to be determined. However, children in areas of endemicity usually have considerably more episodes of diarrhea, which may help to “flush out” the parasite more rapidly. Ten percent of individuals in the South African study and about 3% in the Bangladeshi study showed symptoms of dysentery associated with amebic infection, but none of the study subjects developed an amebic liver abscess during the 12-month observation period. Thus, in agreement with the results presented here, it can be concluded that the vast majority of E. histolytica
carriers from areas of endemicity do not develop amebic disease. Whether this is also true for nonimmune travelers remains to be determined. However, even a relatively low risk for the development of amebic disease, in a range of 2 to 10%, argues for treatment of E. histolytica
carriers, as suggested previously (10
It has been repeatedly reported that travelers usually develop amebic liver abscess several months after returning from areas of endemicity and in some cases even after several years (18
), which suggests a considerable period of parasite persistence. Our average half-life of infection of about 13 months is in agreement with the clinical observations of long latencies between infection and the onset of amebic liver abscess. Extrapolation of the calculated 13-month half-life suggests that even after 5 years, 5% of infected individuals will still harbor the parasite. This long period of persistence may also explain the observed elevated risk for development of recurrent amebic liver abscesses (4
), as in most countries where the parasite is endemic, treatment of invasive amebiasis usually does not include a luminal amebicidal agent.
A particular problem for time course studies on parasite infections in areas of endemicity is the correct determination of the reinfection frequency. We have analyzed the reinfection rate by two independent approaches. First, reappearance of the parasite was detected in individuals successfully treated for E. histolytica
infection, and second, changes in genetic “fingerprints” of E. histolytica
during the course of infection were analyzed. As both methods revealed rather similar results, the calculated annual reinfection rate of about 11.5% in those individuals previously infected with E. histolytica
seems to be a reliable value for the population studied. This value is about 3 times higher than the infection rate in individuals not recently infected with the parasite, which is in line with previous findings that the risk of E. histolytica
infection is not evenly distributed among the study subjects but is dependent on a number of confounding factors, such as level of education or sanitary conditions (4
Several studies have already demonstrated considerable genetic polymorphism among E. histolytica
isolates, even from limited geographic areas (2
). However, only two of these studies have monitored the parasite isolates longitudinally (16
). Thus, it was of particular interest that in addition to a high degree of polymorphism among E. histolytica
parasites from Phu Cat, Hué, the patterns were genetically stable during asymptomatic infection over an observation period of at least 12 to 15 months. Genetic changes in a very small number of cases were most likely the result of new infections rather than spontaneous mutations, as two different independent genomic loci were investigated, and in five of six cases in which changes occurred, both loci were affected. The high genetic stability of amebae within an infected subject may indicate that E. histolytica
infections in Phu Cat are clonal or that in the case of mixed infections, one subpopulation outgrows the other and establishes a long-lasting infection. Thus, we cannot completely rule out the possibility that the analysis of genetic fingerprints has missed new infections that were unable to compete with E. histolytica
parasites already present in the bowel.