[Vaccines blocking transmission].
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Biomedical subjects
Publications and source records attributed to R Sauerwein.
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Cytokines and inhibitors in plasma were measured in 44 patients with typhoid fever. Ex vivo production of the cytokines was analyzed in a whole blood culture system with and without lipopolysaccharide (LPS). Acute phase circulating concentrations of cytokines (+/- SD) were as follows: interleukin (IL)-1 beta, < 140 pg/mL; tumor necrosis factor-alpha (TNF alpha), 130 +/- 50 pg/mL; IL-6, 96 +/- 131 pg/mL; and IL-8, 278 +/- 293 pg/mL. Circulating inhibitors were elevated in the acute phase: IL-1 receptor antagonist (IL-1RA) was 2304 +/- 1427 pg/mL and soluble TNF receptors 55 and 75 were 4973 +/- 2644 pg/mL and 22,865 +/- 15,143 pg/mL, respectively. LPS-stimulated production of cytokines was lower during the acute phase than during convalescence (mean values: IL-1 beta, 2547 vs. 6576 pg/mL; TNF alpha, 2609 vs. 6338 pg/mL; IL-6, 2416 vs. 7713 pg/mL). LPS-stimulated production of IL-1RA was higher in the acute than during the convalescent phase (5608 vs. 3977 pg/mL). Inhibited production of cytokines during the acute phase may be due to a switch from a proinflammatory to an antiinflammatory mode.
Monoclonal antibodies (mAbs) and human sera from gametocyte carriers were applied in the bio-assay to test for their transmission-blocking capacity. Competition ELISA's have been developed for the detection of natural transmission blocking antibodies. Approximately 55% of the sera blocking in the bio-assay gave positive results in these competition ELISA's.
Competition ELISAs have been developed for natural transmission blocking antibodies. Approximately 50% of the sera blocking in the conventional mosquito feeding experiments, gave positive results in these competition ELISAs. Attempts to adapt competition ELISAs to a field application have been partly successful.
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A method for determining the infectious reservoir of malaria (K) and vector survival rate (P) by measuring oocyst size and discriminating between the most recent and other infections is described. In the laboratory the mean diameter of 3 d oocysts in Anopheles gambiae, kept at 26 degrees C, was 11.5 microns and the mean diameter at day 5 was 24.5 microns. Oocyst sizes in wild caught mosquitoes from southern Tanzania, that had fed on the occupants of bed nets with holes in the sides, were more variable. 2060 A. gambiae s.l. and 1982 A. funestus were examined for oocysts 3 d after feeding; 796 and 654 oocysts from the 153 and 170 infected females, respectively, were measured. Because of misclassification errors, the use of a simple cut-off model, in which all oocysts less than 17.5 microns in diameter were considered to have arisen from the most recent feed, was thought to overestimate K and underestimate P. A statistical model which allows for overlap in the oocyst size distributions is described. Estimates of the infectious reservoir derived from this model were 2.8% for A. gambiae s.l. and 4.2% for A. funestus, and the estimated survival rates per gonotrophic cycle were 65.5% and 52.9%, respectively. The utility of measuring oocyst size in naturally infected mosquitoes is discussed.
The standard laboratory test for reduction in malaria transmission is based on the measurement of oocyst numbers in mosquitoes fed on blood meals containing test and control sera. Interpretation of the results, however, is often hampered by the large variation in numbers of infected mosquitoes and oocysts. The objective of this study was to compare 3 measures for the assessment of transmission reduction (so-called R values) and to define the experimental criteria that allow interpretation of the results. To determine variability in R values of control sera, a replicate experiment was performed with 10 non-endemic sera of Dutch blood donors. Furthermore, 2 measures for calculation of transmission reduction were compared in a triplicate experiment using Plasmodium falciparum, Anopheles gambiae and malaria endemic sera. Calculations using the geometric mean of Williams are currently used to identify blocking and non-blocking sera. However, calculations using log-transformed data could distinguish more gradual levels of transmission reduction activity by endemic sera--i.e. blocking, reducing and non-blocking activity. Grading of transmission reduction activity is important for epidemiological studies on transmission immunity and for validation of future transmission-blocking vaccines.
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