Biomedical subjects
Publications and source records attributed to A Voller.
A micro-scale enzyme linked immunosorbent assay for African trypanosomiasis is described. The test uses very small quantities of sera and with T. brucei antigen is sensitive in detecting T. rhodesiense infections in man. Cross reactions occur with antisera to, and antigens of, Leishmania donovani and Trypanosoma cruzi.
A simple microplate method of enzyme linked immunosorbent assay for Rubella antibody is described. This Micro-ELISA was compared with haemagglutination inhibition in a study of 188 human sera. The total discrepancy rate between the two tests was only 3-7%.
Preliminary enzyme-linked immunosorbent assay (ELISA) with serum from a patient with onchoceriasis revealed extensive cross-reactions with various nematode antigens. Further tests on a batch of sera from people with proven O. volvulus infections using O. gutturosa antigen, showed that almost all the sera gave higher ELISA values than did control African sera.
This paper describes the characterization of proteinuria in Aotus monkeys infected with quartan malaria (Plasmodium brasilianum), using a micro-disc-electrophoresis system. In the post infection urine samples, increases in total proteinuria, albuminuria and gamma-globulinuria were noted a few weeks after peak parasitaemia. Two new proteins also appeared in the urine of malaria infected animals. These findings are discussed with reference to the belief that the Aotus-P. brasilianum system can be a model for human malaria in renal immunopathology.
This paper describe the renal pathology in Aotus trivirgatus (owl monkeys) following P. falciparum infections and also when the initial P. falciparum was followed by infection with P. malariae or P. brrasilianum. Acute P. falciparum infections were associted with high parasitaemia but relatively mild changes in the glomeruli. This was also the case when a second infection with P. falciparum was given after the first infection had been terminated with chloroquine. Four monkeys with multiple infections involving P. Malariae or P. brasilianum after P. falciparum showed a glomerulonephritis. Two of these also showed a necrotizing arteriolitis. The findings suggest that P. falciparum alone does not give progressive renal disease and that this is more likely to occur with mixed infections.
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Antibodies with different spectra of reactivity are produced during malarial infections and marked changes in IgG and IgM levels occur. In addition malaria elicits serological changes that are usually associated with connective tissue disease. The excessive anaemia associated with malaria may, in part, be an autoimmune phenomenon. Transient nephritis accompanies many plasmodial infections but chronic malarial nephrotic syndrome is specifically associated with quartan malaria. Malarial infection leads to splenomegaly, the most extreme form of which is idiopathic tropical splenomegaly, which probably represents an aberrant immune response to the infection. Malaria can affect the humoral immune response to unrelated antigens and infectious agents. This may be relevant to the etiology of Burkitt's lymphoma. During pregnancy there is some loss of acquired immunity to P. falciparum and the placenta appears to be an immunologically privileged site for the multiplication of this parasite.
A microplate method of enzyme-linked immunosorbent assay is described. This method, which may be of value in the measurement of antibodies in various infectious diseases, is simple, cheap, and easy to carry out on a large scale. For field use, results can be assessed subjectively. The potential of the test is illustrated by a small seroepidemiological study of malaria.
In a study in a population in northern Tanzania, almost all adults and schoolchildren with parasitaemia were positive in the PHA test, whereas only half of the children under 5 years of age with parasitaemia were serologically positive. A second study on infants up to the age of 18 months confirmed that many young children who could be expected to have been exposed to malaria did not have PHA-detectable antibody.
The specificity of the indirect haemagglutination (IHA) test with Plasmodium falciparum placental antigen-sensitized test cells was examined with sera from healthy blood donors and from patients with diseases other than malaria. Only 1 nonspecific antibody reaction was seen in more than 700 tests. A comparison of IHA titres and indirect fluorescent antibody (IFA) titres with IgG and IgM conjugates on 503 sera from inhabitants of Mto Wa Mbu in Tanzania showed in successive age groups an increasing number of seropositive reactors with both tests. The increase in the proportion of positive reactions and in the mean titre levels started earlier but was more gradual in the IFA test than in the IHA test. Parasite carriers had higher antibody levels than people without an apparent parasitaemia. Parasite carriers in the younger age groups especially were more frequently seronegative in the IHA test than in the IFA test with anti-IgG conjugates. The reactivity of the IHA test with P. falciparum (Palo Alto/Aotus) antigen was higher than that with P. falciparum placental antigen and was thus closer to that of the IFA test with IgG conjugates.
Analysis of various isolates of Plasmodium falciparum from East and West Africa and from South-east Asia showed that some of the parasite enzymes can exist in more than one electrophoretic form. At least one form of each enzyme was common to parasites from all three regions. The enzyme forms could be used to differentiate morphologically indistinguishable samples of P. falciparum.
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