Abstract
The aim of using this model with marginal vitamin A deficiency in the absence of protein-energy malnutrition and secondary infection, was to provide a better insight into the role of vitamin A deficiency per se in the relationship with infection and in particular whether an interaction existed between vitamin A status and NDV infection.
In Chapter 1, the current knowledge of vitamin A deficiency in relation to morbidity and mortality is summarized with special emphasis on measles infection, together with a description of the animal model used and the specific aims of this thesis.
In Chapter 2, a method is described for producing marginally vitamin A-deficient chickens capable of remaining healthy for an extended period, without showing clinical signs of vitamin A deficiency. The principle of this method consisted of working with two generations of chickens, in which laying hens were fed a diet with a limited vitamin A content for a period of approximately 3 months in order to obtain day-old chickens which were marginally deficient in vitamin A.
In Chapter 3, experiments demonstrating an interaction between vitamin A status and NDV infection are presented. On the one hand, infection with NDV resulted in an increased rate of morbidity in marginally vitamin A-deficient chickens when compared with chickens fed adequate amounts of vitamin A. On the other hand, plasma retinol concentrations in chickens which were already marginally vitamin A- deficient prior to infection showed a significant decrease after infection when compared with that in their noninfected counterparts fed the same diet.
In Chapter 4, studies are reported in which an attempt is made to explain by which mechanisms NDV infection can lower plasma retinol levels in chickens which were marginally vitamin A-deficient prior to inoculation. Although it was not investigated directly, a plausible explanation for this phenomenon appeared to be an increased rate of utilization and catabolism of retinol and retinol-binding protein (RBP) by extrahepatic tissues, together with a direct effect of the virus on RBP metabolism in liver.
In Chapter 5, studies on the specificity of NDV infection in the interaction observed are reported using a similar model, in which NDV has been replaced by infectious bronchitis virus (IBV) or reovirus (RV). Since IBV infection resulted in a similar interaction with vitamin A status, it is concluded that the interaction between vitamin A status and NDV infection is not specific for NDV. However, the mechanism by which N DV can reduce vitamin A status appears to be, at least partly, specific.
In Chapter 6, studies demonstrating that both vitamin A deficiency and NDV infection affect lymphoid organs and circulating lymphocytes are presented. Vitamin A deficiency resulted in marked lymphopenia and this was even more pronounced during the acute phase of NDV infection.
In Chapter 7, results are reported of experiments examining the effect of vitamin A deficiency on Cytotoxic T lymphocyte (CTL) activity to NDV as this is one of most important cell-mediated defense mechanisms to viral infection and necessary for recovery from NDV infection. Vitamin A deficiency resulted in significantly reduced CTL activity to NDV. In addition, the results also showed a diminished pool of CTLS in vitamin A deficiency.
In Chapter 8, results of the studies showing that vitamin A deficiency does not affect the hemagglutination-inhibition antibody response to NDV are presented. However, following immunization with selected antigens differing in thymus dependency, the level of the primary and secondary IgG response to bovine serum albumin (BSA) and of the primary IgG response to sheep red blood cells (SRBC) and Brucella abortus (BA) was reduced. However, the secondary Igm response to SRBC and BA was slightly elevated by vitamin A deficiency. NDV infection reduced primary IgM and IgG responses to SRBC and BSA but not to BA when immunization was carried out during the acute phase of disease. This suggests a defect in T-helper cell function. The combination of vitamin A deficiency and NDV infection resulted in the lowest IgG titers to T-cell-dependent antigens.
In Chapter 9, experiments are described which demonstrate that vitamin A deficiency impairs microbicidal activity and to a lesser extent phagocytosis by peritoneal macrophages in both infected and noninfected chickens. Infection with NDV increased phagocytosis and microbicidal activity in both vitamin A-deficient chickens and their counterparts fed adequate vitamin A. In general, this effect was more pronounced in the latter group.
In Chapter 10, investigations on the effect of vitamin A deficiency and NDV infection on mucosal immunity are reported. Vitamin A-deficient chickens had significantly lower levels of IgA in bile and this was even more pronounced in combination with NDV infection. However, the number of IgA-containing plasma cells in mucosal tissues was not affected by vitamin A deficiency and only slightly increased by NDV infection. These results, together with slightly increased levels of IgA in plasma of vitamin A-deficient chickens, suggest that the hepatobiliary transport of IgA has been
impaired in vitamin A deficiency and NDV infection but disturbed synthesis of IgA in plasma cells or its subsequent release or both could not be ruled out.
In Chapter 11, a general discussion with some concluding remarks is presented. The demonstration of the existence of an interaction between vitamin A status and NDV infection is an important observation in this thesis. It appeared that pre-existing marginal vitamin A deficiency per se without concomitant protein-energy malnutrition can result in a severe form of NDV infection and that even a mildly pathogenic strain of NDV can reduce vitamin A status from marginally deficient to deficient. This interaction results in a vicious circle, in which it is difficult to separate cause and effect but might eventually lead to death. A similar interaction has been proposed for vitamin A status and measles infection in humans. However, the biggest difference between the results observed in our model and that of measles infection in developing countries is that, unlike the situation with children infected with measles in developing countries, the chickens used in our model did not suffer from protein-energy malnutrition. In addition, measles virus itself has a more marked effect on food consumption and absorption of nutrients in the gastrointestinal tract, and is more immunosuppressive than the NDV strain used in our model. Nevertheless, our results do indicate that the role of vitamin A deficiency in severe measles infection may be more important than sometimes is suggested. moreover, the results also show that even marginal vitamin A deficiency can affect host defense mechanisms ranging from nonspecific processes to various aspects of systemic and mucosal immunity. Thus primary infections such as measles become more severe and secondary infections often become established more readily. As marginal vitamin A deficiency is observed in a large part of the population in many developing countries, it may have serious consequences for public health.
Original language | English |
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Qualification | Doctor of Philosophy |
Awarding Institution | |
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Award date | 8 Sept 1989 |
Place of Publication | Wageningen |
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DOIs | |
Publication status | Published - 8 Sept 1989 |
Keywords
- veterinary science
- measles
- rubella
- chicks
- retinol
- newcastle disease
- developing countries
- cum laude