The Impact of Intestinal Helminths on Mammalian Nutritional Physiology

A critical review of the literature (Section 1) interprets evidence to show how various mammalian intestinal helminth infections have been associated with alterations in the nutritional physiology of the mammalian host. The effects have been observed during all stages of metabolism, from initial ingestion through all the intra-luminal events, including digestion and nutrient absorption, and finally to the post-absorptive events of intermediary metabolism, and the mechanisms appear to be as diverse as structural histopathologic changes and alterations in the concentrations of circulating hormones. An experimental investigation of interactions between rat host metabolism and infection with Nippostrongylus brasiliensis (Nematoda), (Section 2), was conducted. Plasma glucose concentrations were observed to fall between days 6 - 14 p. i. of a primary infection of rats with N. brasiliensis, and although food intake was also observed to fall during this intake, with marked troughs on days 3 and 9 p. i. , this is considered to be no more than contributory to the reduced plasma glucose concentrations. Measurements of the activity of the hepatic gluconeogenic enzyme alanine-amino-transferase (ALT), by in vitro assay, during N. brasiliensis infections revealed striking fluctuations. An elevation followed by a reduction in the activity of the enzyme was observed, and these alterations were found to be dose-dependent. In secondary infections similar fluctuations were observed, but appeared to be attenuated. A reduction in the activity of the enzyme was detected when the infection was initiated by oral transfer of adult N. brasiliensis worms, but when an infection initiated by subcutaneous inoculation of N. brasiliensis larvae was terminated on day 4 p. i. by anthelmintic treatment, ALT activity measured on day 10 p. i. was not found to be different from that measured in control rats. Addition of parasitic homogenate to the liver assay caused no change in the measurements, but addition of serum was associated with a decrease in the ALT activity measured, and this was particularly marked with serum from immune rats. These results suggested that an immune response of the host to the N. brasiliensis infection may be influencing ALT activity. Measurements of hepatic ALT activity in immunosuppressed rats infected with N. brasiliensis supported this theory. Accordingly measurements were made in rats during N. brasiliensis infections of parameters known to be indicators of an immune response involving cytokines, known to influence a number of aspects of metabolism (Klasing, 1988). Although body temperature, leukocyte numbers and plasma zinc concentrations provided no evidence of an immune response involving cytokines, a marked elevation in the concentration of plasma a2-macroglobulin was observed, suggesting that cytokines may be produced. Measurements of plasma corticosterone concentrations during both primary and secondary N. brasiliensis infections in rats revealed fluctuations in concentration that provided a tempting suggestion that alterations in concentrations of this immunosuppressant hormone may be contributing to the fluctuations in ALT activity described. The possibility that metabolic fluctuations may be a "trade off" for an effective immune response is discussed in terms of these results. A collaborative study of a human community in Cocle Province, Panama (Section 3) was undertaken to investigate associations between nutritional variables, in particular vitamin A status, and soil-transmitted helminth infections in primary school children, with measurements being made of nutritional parameters both before and after anthelmintic intervention. The epidemiological data collected revealed that Ascaris lumbricoides, hookworm and Trichuris trichiura were the most common intestinal helminth infections observed, with prevalences of 18.2, 12.0 and 27.5% respectively. This data could be compared not only to results of intestinal helminth surveys conducted in the same area over the past 60 years, but also to more contemporary data from various regions of Central America. The efficacy of levamisole as a control measure was assessed, and considered to have an effective role. Plasma retinol concentrations were not found to be indicative of vitamin A deficiency, and no association between lower concentrations and intestinal helminths was detected. Over 20% of the children, however, were found to have blood haemoglobin concentrations indicative of anaemia, and concomitant infections of T. trichiura and hookworm were considered to be contributory. Heavier infections of T. trichiura were also found to be associated with lower anthropometric variables. These results suggest that even relatively light infections of soil-transmitted helminths may exert an insidious effect on the nutritional status of growing children, despite the availability of adequate nutritional resources.