Browsing by Author "Lee A"

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    Field performance of a thin-layer chromatography assay for detection of nevirapine in umbilical cord blood.
    (2006) Chi BH; Lee A; Acosta EP; Westerman LE; Sinkala M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    PURPOSE: Although cord blood surveillance can measure the effectiveness of nevirapine (NVP)-based programs for the prevention of mother-to-child HIV transmission (PMTCT), it requires the ability to detect nevirapine in plasma. At present, the only validated method is high-performance liquid chromatography (HPLC), a technique poorly suited for most resource-constrained settings. METHOD: We evaluated the field performance for a simple and inexpensive thin-layer chromatography (TLC) assay for NVP detection. We developed a conditional probability model to compare 2 testing algorithms: HPLC alone, and TLC screening followed by HPLC confirmation of negative results. RESULTS: When compared to HPLC, sensitivity of TLC was 0.67 (95% confidence interval [CI] 0.49-0.84) and specificity was 0.84 (95% CI 0.69-0.95). In this sample - where overall NVP coverage was 49% - positive predictive value was 0.80 and negative predictive value was 0.72. At baseline with population NVP coverage of 33%, cost per specimen was lower in the TLC-HPLC testing algorithm (40 dollars vs. 50 dollars), and the proportion of false results was acceptable (11%). As population NVP coverage increased, cost-efficiency improved and error rate dropped substantially. CONCLUSION: TLC is reasonably sensitive and specific for NVP detection. A 2-step testing algorithm incorporating TLC and HPLC provides cost-efficiency at little expense to test performance.
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    Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines.
    (2018-Jun-27) Mwanza-Lisulo M; Chomba MS; Chama M; Besa EC; Funjika E; Zyambo K; Banda R; Imikendu M; Sianongo S; Hancock REW; Lee A; Chilengi R; Stagg AJ; Namangala B; Kelly PM; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.; Institute of Distance Education, University of Zambia, Lusaka, Zambia.; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia. Electronic address: mpalamwanza123@gmail.com.; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia.; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia; Department of Chemistry, University of Zambia, Lusaka, Zambia.; University of British Columbia, Vancouver, Canada.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.
    All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers α4β7 integrin and CCR9 on lymphocytes, increasing their gut tropism. Here, we show that, in healthy adult volunteers, ATRA induced an increase of these gut homing markers on T cells in vivo in a time dependent manner. The coordinated increase of α4β7 and CCR9 by ATRA was seen in 57% (12/21) of volunteers and only when given together with an oral Vivotif vaccine. When this coordinated response to ATRA and Vivotif vaccine was present, it was strongly correlated with the gut immunoglobulin A (IgA) specific response to vaccine LPS (ρ = 0.82; P = 0.02). Using RNA-Seq analysis of whole blood transcription, patients receiving ATRA and Vivotif in conjunction showed transcriptomic changes in immune-related pathways, particularly including interferon α/β signaling pathway, membrane-ECM interactions and immune hubs. These results suggest that exogenous ATRA can be used to manipulate responses to a subclass of oral vaccines, so far limited to a live attenuated Vivotif vaccine.