Amebiasis resulted in a substantial burden of illness. One-fifth of the children suffered from E. histolytica
-associated diarrhea or dysentery. This high incidence contradicts conventional wisdom that amebiasis is “a very infrequent cause of childhood diarrhea or dysentery in developing countries” (6
). Both infection and diarrhea associated with E. histolytica
were predominantly self-limited, with only 19% of episodes of E. histolytica
-associated diarrhea requiring metronidazole therapy.
Contributing to the burden of amebic infection in these children were reinfections, similar to other enteric infections (4
). The 4.2-year period of every-other-day observation and the use of highly specific diagnostic tests for amebiasis demonstrated the existence of partial immunity to disease and infection. Immunity was associated with an intestinal IgA response specific for the active site (CRD) of the major parasite adhesin.
There are several possible limitations of this study. The morbidity of amebiasis was likely underestimated because of interventions that included every-other-day family visits by health assistants, oral rehydration, and provision of antiamebic and antibiotic therapy, all at no cost to the children and their families. Immunity associated with anti-CRD IgA may also have been underestimated because of the 4-month sampling interval used to detect IgA in the study. Additionally, the incidence of amebiasis may have been underestimated, since stool specimens were not always available to be tested for E. histolytica. Although this natural history cohort has extensive and comprehensive follow-up, this was an observational study, and there is the possibility of residual confounding from unmeasured or unknown factors. There is also the potential for selection bias, since only 289 children out of 1,164 were selected for inclusion in the study. However, we believe the children included in this study are representative of an urban slum population, for except for the entry criterion that 50% of the children be anti-E. histolytica IgG positive, no enrollment limitations were made. To avoid potential bias, we included baseline anti-E. histolytica IgG status as a covariate (where appropriate) in our analyses.
The ratio of symptomatic to asymptomatic amebiasis was low, as has been previously observed with children and adults (7
). Parenthetically, no hepatic abscesses were detected during the prospective study, which was expected, since amebic liver abscess is predominantly a disease of adult males (18
). We do not know the relative contributions of acquired immune responses versus differences between E. histolytica
strains to the low rate of invasive infections. Enrollment of a birth cohort in this prospective study is planned to address the former. However, we doubt that invasive disease is more common in children under the age of 2, since it is rare for this age group to be admitted to the International Centre for Diarrheal Disease Hospital of Dhaka with amebiasis (14
Reinfection with E. histolytica
was common in this cohort and has also been observed in adults in Vietnam (7
). In the case of rotavirus, where reinfection is also common, the lack of complete cross-protection between circulating rotavirus strains is a contributing factor. Extensive genetic diversity exists between E. histolytica
isolates in Mirpur, Vietnam, and South Africa (2
). Intraspecies diversity, combined with the transient acquired immunity observed here, likely contributes to the high incidence of reinfection.
The poor sanitary conditions in Mirpur undoubtedly contributed to the high incidence of infection and reinfection. Mirpur is unfortunately not atypical of the conditions in the developing world: the World Health Organization estimates that 2.4 billion people worldwide are without access to improved sanitation and 1.1 billion lack access to improved water. Universal access to water and sanitation would likely result in dramatic reductions in morbidity and mortality not only from amebiasis but from most enteric infections. Enormous strides have been made in the last decade, but these efforts are keeping only slightly ahead of population growth (37
This study extends the observation that a mucosal anti-CRD IgA response is associated with resolution of existing infection and in a delay of repeat infection (15
). The 4-year length of the study allowed the discovery that immunity associated with fecal anti-CRD IgA was short-lived but importantly was associated with protection not only from infection but from disease. Also encouraging for the potential application of CRD in a subunit vaccine was the lack of any HLA class II association with the ability of children to mount an anti-CRD IgA response observed here, as well as previous observations of its sequence conservation between isolates of E. histolytica
and utility as a subunit vaccine in animal models of amebiasis (3
It is remarkable that during the 4 years of the study, some of the children were never detected to have E. histolytica
infection. This contrasts not only with the high rate of reinfection with E. histolytica
in the infected children but also with the 98% infection rate of the same children with the nonpathogen E. dispar
. Genetic differences between children may be playing an important role in influencing susceptibility to amebiasis, if the environmental factors that contribute to infection with E. histolytica
and E. dispar
are similar. The finding that children with three observed infections were at greater risk for additional new infections also suggests that there are host factors that influence susceptibility to amebiasis. Supporting a contribution of host genetic factors to susceptibility is the previous finding of an association of the HLA haplotype DQB1*0601/DRB1*1501 with a delay in infection onset (12
). Future discovery of other genes influencing susceptibility to amebiasis will be enlightening as to the immune responses that provide protection.
In summary, the major conclusions of our study are that amebiasis is common in these urban slum children and that immunity to amebic diarrhea and colitis exists. The substantial burden of disease due to E. histolytica suggests that an effective vaccine would result in a measurable improvement in child health.