Drug resistance of strains of Mycobacterium tuberculosis isolated in Brazil.

Tuberculosis remains a serious public health problem, worsened by an increased frequency of multidrug-resistant Mycobacterium tuberculosis. We report here a retrospective study of resistance to antituberculosis drugs of 170 strains of M. tuberculosis isolated from the state of Rio Grande do Sul, Brazil. The frequency of resistance to at least one drug was 34%, while 22% were resistant to more than one drug. Among the strains isolated from patients without a history of previous treatment for tuberculosis, patients with positive serology for HIV and patients with previous treatment for tuberculosis, the resistance to at least one drug was 14, 27 and 73%, respectively. Multidrug-resistant tuberculosis, defined as resistant to at least rifampicin (RMP) and isoniazid (INH), was found in the groups of patients without previous treatment, HIV co-infected and with previous treatment for tuberculosis at 10, 17 and 44%, respectively. With the purpose of evaluating whether the sensitivity test to INH and RMP would be a good marker to indicate resistance to other antituberculosis drugs, sensitivity tests were performed with four more drugs in 32 strains, initially classified as resistant to INH, RMP or both. Of 18 strains resistant to INH and RMP simultaneously, 89% showed resistance to four more drugs.

Congenital trypanosomiasis in a child born in London.

A female infant of 22 months was referred to the Hospital for Sick Children, London, because of delayed psychomotor development. Extensive investigations revealed no cause, but eventually trypanosomiasis was diagnosed. The infant had not been outside the UK, but her mother came from Zaire, where the disease is endemic, but had lived in Kinshasa, where there is no sleeping sickness. It is thought, that the mother may have been asymptomatically infected by a fresh-blood transfusion four years earlier, since no other source of infection was apparent.

Macromolecular absorption of food antigens in health and disease.

During the neonatal period, the development of the mucosal barrier against penetration of bacteria, toxins and antigens is an important protective mechanism against a variety of pathologic conditions such as inflammatory and allergic reactions. The closure of the gut with regard to the uptake of food antigens in macromolecular form is determined by non-immunologic mechanisms as well as by the immunologic system of the gut. Animal experiments show that various diseases affecting the gut may interfere with intestinal antigen handling. As a result, susceptibility to infection and allergic reactions may ensue. Studies performed in humans show that selective IgA deficiency, preterm delivery, intestinal helminth infection and type of feeding during the neonatal period may influence antigen uptake by the intestinal epithelium. These conditions, as well as various diseases affecting the gut, may cause increased absorption of intraluminal antigens and result in the triggering of allergic type responses.

Intestinal antigen handling at mucosal surfaces in health and disease: human and experimental studies.

Intestinal uptake of antigenically intact food proteins was measured by a solid phase radioimmunoassay on serum samples after instillation of food proteins into a closed intestinal loop of adult Wistar rats. Compared to normal controls, rats fed protein deficient diets during five months had a higher macromolecular uptake. During the course of Nippostrongylus brasiliensis infection this uptake was decreased. In cholera toxin induced secretory states of the intestinal mucosa uptake of food proteins was increased. In human studies the uptake of Beta-Lactoglobulin after a milk meal was shown to be increased in premature compared to full-term neonates. In children suffering from intestinal helminth infection the macromolecular uptake was higher before treatment compared to that after treatment. These studies show that various pathological situations can alter the antigen handling at mucosal surfaces.

A simple and rapid flow cytometric method for routine assessment of baker's yeast uptake by human polymorphonuclear leukocytes.

A new method for measuring uptake of baker's yeast (BY) by human polymorphonuclear leukocytes (PMN) using flow cytometry is described. The method correlates excellently with the visual method, is reproducible and provides a means for investigating the early phases of the phagocytic process as well as the phagocytic capacity of PMN. This quick and accurate method allows the counting of large numbers of cells, and monitoring of the process of particle uptake and has a considerable potential in the routine assessment of polymorph function in various clinical situations.

Specific antigen exclusion and non-specific facilitation of antigen entry across the gut in rats allergic to food proteins.

The intestinal absorption of ovalbumin and beta-lactoglobulin was measured in Hooded Lister rats which had previously been made allergic to ovalbumin, and in unimmunized controls. The antigens were introduced both together and separately into closed intestinal loops. Absorption of free ovalbumin, but not beta-lactoglobulin, was reduced in rats with anti-ovalbumin antibody, demonstrating antigen-specific immune exclusion despite the presence of reaginic antibody. In contrast, the absorption of beta-lactoglobulin was enhanced by the presence of ovalbumin in rats with IgE anti-ovalbumin, but not in unimmunized controls. These results suggest that macromolecular absorption may be increased in an antigen non-specific way in food allergy.

The effect of protein deficiency on the development of chronic antigen-antibody complex disease in mice.

Mice genetically selected to produce antibodies of either high or low affinity to protein antigens injected in saline were fed either a normal protein diet or a protein-deficient diet and were given daily injections of HSA for up to 73 days to induce chronic antigen-antibody complex disease. In low-affinity mice fed the normal protein diet, this resulted in impairment of renal function, deposition of immunoglobulin, C3 and HSA in the glomeruli, high levels of circulating antigen-antibody complexes and death from apparent renal failure in 50% of the animals. High-affinity mice on either diet had no impairment of renal function, fewer deposits in the glomeruli, lower levels of circulating complexes and no deaths. Low-affinity mice fed the protein-deficient diet had less impairment of renal function and less glomerular deposition of complexes than did low-affinity mice fed the normal diet. In addition, none of these mice died from renal failure. These results demonstrate that the protein-deficient diet reduced the severity of the experimental chronic antigen-antibody complex disease in low affinity mice but did not increase the susceptibility of high-affinity mice to the disease.

The cord serum free amino acid levels in appropriate and small for gestational age newborn infants of mothers without clinical malnutrition in Abidjan.

The cord serum amino acid levels were determined in nine small for gestational age and fourteen appropriate for gestational age newborn infants of Abidjan, Ivory Coast. Small for gestational age newborns had a significantly lower total amount of amino acids, but the characteristic deviation of the individual concentrations and the high glycine/valine ratio seen in experimental and clinical protein deficiency were not found.

Antibody affinity and clearance function studies in high and low antibody affinity mice. The effect of protein deficiency.

The effect of dietary manipulation on the relationship between macrophage clearance function and antibody affinity has been investigated in genetically selected high and low affinity mice. The results confirm that protein deprivation reduces the clearance rate of polyvinylpyrrolidone (Kpvp) and the relative affinity (Kr) of antibody to human serum albumin in mice normally producing high affinity antibody. Although protein deprivation of mice of the low affinity line reduced Kpvp, the mean Kr was not altered. Furthermore, although the two lines had significant differences in Kr values there were no demonstrable differences in macrophage clearance function as assessed by clearance of PVP, radiolabelled aggregated IgG and preformed antigen-antibody complexes. Analysis of values of Kr and Kpvp in individual animals indicated that these two parameters are not correlated. These experiments, provide further evidence for the profound effect of dietary manipulation on the immune response and suggest that in these genetically selected mice at least, the genetic control of antibody affinity is exerted at a level other than that measured by macrophage clearance function tests.

The genetic control of antibody affinity. Evidence from breeding studies with mice selectively bred for either high or low affinity antibody production.

The genetic control of antibody affinity has been studied in mice selectively bred on the basis of the affinity of antibody they produce to protein antigens injected in saline. Two lines of mice have been obtained, one producing predominantly high and the other predominantly low affinity antibody. Breeding experiments have been performed with these two lines after ten generations of selection and the level and affinity of antibody to protein measured in parents, F1 hybrids and backcross offspring. The results indicate that antibody affinity is a genetically controlled parameter of the immune response and that this control is exerted independently of that controlling antibody levels. Furthermore, high and low affinity line mice have been typed for major histocompatibility complex antigens and the results show that the two lines are not significantly different. This therefore suggests that genes controlling antibody affinity are not linked to the major histocompatibility locus.