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The objectives of this study were to determine the effect of different types and levels of dietary fiber on Heligmosomoides polygrus (Nematoda) in laboratory mice. BALB/c mice were randomly assigned to one of seven diets: no fiber, cellulose (5%, 10%, 20%), and pectin (5%, 10%, 20) and infected with H. polygyrus one week later. The length of intestine increased significantly with the concentration of pectin and was associated with longer villi, thicker mucosa and increased villus/crypt ratio. In contrast, changing concentration of cellulose had minimal effects on the gastrointestinal tract. More day 5 larvae were found in mice fed 20% pectin, but neither type nor level of dietary fiber affected worm survival or spatial distribution. An increase from 5% to 10% pectin increased per capita egg production both in vivo and in vitro, but a further increase to 20% pectin decreased per capita egg production in vivo to the low level seen in mice fed no fiber. However when the parasites from mice fed 20% pectin diet were cultured in vitro, they released very high numbers of eggs. Changing concentration of cellulose had no effect on parasite egg production in vivo or in vitro. Our study supports the hypothesis that pectin promotes the establishment and reproduction of Heligmosomoides polygyrus, and that this is closely related to the changes in gut morphology. Therefore we conclude that cellulose, not pectin, should be used to balance reduced content of macronutrients in studies on malnutrition and nematode infection.

The effect of low dietary zinc on the survival and reproduction of an intestinal nematode (Heligmosomoides polygyrus) during both primary (Experiment 1) and challenge (Experiment 2) infections was investigated. Plasma zinc concentrations were significantly lower in mice fed a 5 ppm zinc diet (ZR), compared with control mice fed a 60 ppm zinc diet (C) in both experiments. There were no significant differences between ZR and C mice in any other zinc parameter or on worm burdens or worm fecundity in either experiment. Comparisons between the primary infection and the challenge infection did suggest a possible effect of calorie restriction on worm burdens. / Parasitic infection did, however, affect the host nutritional status. Spleen weight was significantly higher in infected mice in both experiments. In the challenge infection, both liver and spleen copper concentrations were significantly higher, and spleen iron concentration significantly lower in the infected mice. That these significant results were seen only in the challenge infection may suggest the role of the host immune response.

Geohelminthiasis is a serious problem in city slums and despite being easily treatable in the short term, its elimination enjoys a low priority by parents, teachers and public health authorities. This is partly due to the greater emphasis given to the AIDS and TB programmes. This study of the prevalence, intensity, and reinfection rates of single and multiple geohelminth (Ascaris lumbricoides, Trichuris trichiura and Necator americanus) infections in young children living in slums (informal settlements) in the Durban Unicity is a first for an African city and one of few similar studies anywhere in the world. The geohelminth status was assessed by means of a baseline survey of ten different slums, followed by two further surveys, one after 4Y:z - 6 months and another after 12 months. Infections were measured by microscopic examination of faeces before and after chemotherapy, and risk factors within and between slums were identified by means of a quantifiable questionnaire. The study showed that: 1. The slums have a high endemicity and transmission rate of geohelminth infections. 2. The sub-tropical climate and environment ensured a high survival rate of infective stages. 3. A. lumbricoides had a high prevalence and intensity, followed by T. trichiura with a moderately high prevalence and light intensity. A small proportion of children had intensities of these helminths an order of magnitude higher than previously recorded from rural areas of South Africa. N americanus had a very low prevalence and a very light intensity. 4. Egg output from follow-up 1 to follow-up 2 increased 4.6 fold for A. lumbricoides and 9.4 fold for T. trichiura. 5. Albendazole proved to be a very effective drug against A. lumbricoides and N americanus but not as effective against T. trichiura. 6. The infection and reinfection rates of A. lumbricoides and T. trichiura proved to be influenced by different risk factors. 7. The most important risk factors included topographical position of the slum, quality of the dwelling, number of inhabitants, geophagy and source of fruit and vegetables. II Whereas the ideal solution to the geohelminth problem in the slums would be to upgrade the slum and its inhabitants, this is not an immediately viable option. The challenge of geohelminth control in these slums must be to determine the degree of environmental contamination by human faeces containing infective eggs, to ascertain the survival rate of the eggs and larvae and to implement a control programme together with suitable education of the inhabitants. The Parasite Control Programme should take into consideration that many slum-dwelling children do not go to school and need to be treated at home. A further factor that will have to be taken into account is that lack of influx control to urban areas will mean the continual reinfection of slum-dwellers by the movement from the rural areas. / Thesis (Ph.D.)-University of Natal, Durban, 2001.

Protein deficiency may increase susceptibility to gastrointestinal (GI) parasitic infections, possibly as a result of impaired systemic and/or intestinal effector responses induced by downregulation of Th2 cytokines and/or upregulation of Th1 cytokines. To test this hypothesis, female BALB/c mice (n = 18/diet) were fed a control (24%), marginal (7%), or deficient (3%) protein diet and given a challenge infection with the GI nematode, Heligmosomoides polygyrus. The 3% mice had higher worm burdens at 1, 2 and 4 weeks post-challenge infection (pci), lower increases in serum IgE, reduced intestinal eosinophilia, and depressed mucosal mast cell proliferation and activation at 1 to 2 weeks pci. To determine whether these suppressed effector responses in the 3% mice were associated with altered spleen and mesenteric lymph node (MLN) cytokine profiles, cells were restimulated in vitro with parasite antigen and cytokine concentrations were measured. Deficient MLN cells secreted significantly less IL-4 and more IFN-gamma at 1--2 weeks pci than did control MLN cells. Deficient spleen cells also secreted more IFN-gamma at 2 weeks pci compared with control spleen cells. From RT-PCR analyses, the 3% mice also had lower IL-4 mRNA expression in spleen and MLN at 1--2 weeks pci. Our study supports the hypothesis that protein deficiency exacerbates the survival of a GI nematode parasite by decreasing IL-4 (Th2) and increasing IFN-gamma (Th1) early in the infection, leading to reduced gut and systemic Th2 effector responses.

The influence of energy restriction on the transmission dynamics of a direct life cycle nematode, Heligmosomoides polygyrus, within free-running arena Systems has to date remained unexplored. Indoor populations of CD-1 outbred mice were established for 12 weeks in arenas and fed either energy-suffi ci ent (ES) or energy-restricted (ER-20% réduction in metabolizable energy) diets. Infection was introduced to ail arenas following 3 weeks of diet treatment. Contrary to previous findings, the mice fed the ER diets compensated for the deficiency by increasing food consumption and thus, while early in the experiment energy restriction was evident, dietary effects were no longer observed after 6 weeks. Worm burdens, measured at 4 time points over the course of the experiment, were higher in mice fed the ES diets. Although mice fed the ER diets had greater contact with infected areas, the mice fed the ES diets increased the duration of behaviours that heighten ingestion of the parasite - self and allogrooming. Dietary effects on behaviour were observed only after infection was introduced and were more pronounced in the durations of individual bouts rather than in overall durations or time budgets. Nesting bouts were prolonged in mice in the ER arenas perhaps as a means of thermoregulation to counteract the combined effects of infection and energy restriction. The duration of exploratory bouts was also higher in the ER mice possibly due to an inability to receive or process information in their environment. Social interactions, predominantly involving sniffing, increased after infection was introduced, supporting the rôle of odour in communicating infection status in same-sex conspecifics. Together these results provide a more comprehensive ethogram of mice in a semi-natural setting and highlight those behaviours where adaptive plasticity allows response to dietary and infection stresses.

Interactions among zinc deficiency, energy restriction, immunity and Heligmosomoides polygyrus (Nematoda) infection in mice were investigated. Mice were fed zinc-sufficient (Zn+: 60mg zinc/kg diet), zinc-deficient (Zn$-$: 0.75 mg/kg) or pair-fed (PF) diets. Liver and serum zinc concentrations were reduced in Zn$-$ mice, but zinc content of worms was unaffected by host diet. Both zinc deficiency and energy restriction accelerated worm maturation during a primary infection, but zinc deficiency caused stunting of female worms. Energy restriction led to a anteriorad distribution of worms along the intestine whereas zinc deficiency led to a posteriorad distribution. Enhanced parasite survival in Zn$-$ and PF mice was associated with a decreased immune response in both primary and challenge infections. In the primary infection, spleen cell production of interleukin-4 (IL-4) and interferon-gamma (IFN-$ gamma$), peripheral eosinophilia and serum levels of IgE and IgG1 were reduced by zinc deficiency, whereas the reduced delayed type hypersensitivity (DTH) response and impaired interleukin-5 (IL-5) production were attributed to energy restriction. In the challenge infection, reduced antibody levels (total IgE and IgG1, parasite-specific IgG1 and IgG3) and eosinophilia were attributed to zinc deficiency whereas the higher worm numbers were attributed to a combined effect of zinc deficiency and energy restriction. Although the absolute number of spleen cells was reduced in both Zn$-$ and PF mice, neither deficiency altered the proportion of the cell subpopulations. In vitro functional assays in response to parasite antigen (Ag) revealed that T cell proliferation was reduced by a direct effect of zinc deficiency on T cells, and by the effects of energy restriction on antigen presenting cells (APC). Impaired cytokine production in Zn$-$ mice was more complex. Zinc deficiency reduced T cell function (IL-4 production), energy restriction decreased T cell (IFN-$ gamma$ productio