Browsing by Author "White, Nicholas J"

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    Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria
    (2014-12-09) White, Nicholas J; Ashley, Elizabeth A; Recht, Judith; Delves, Michael J; Ruecker, Andrea; Smithuis, Frank M; Eziefula, Alice C; Bousema, Teun; Drakeley, Chris; Chotivanich, Kesinee; Imwong, Mallika; Pukrittayakamee, Sasithon; Prachumsri, Jetsumon; Chu, Cindy; Andolina, Chiara; Bancone, Germana; Hien, Tran T; Mayxay, Mayfong; Taylor, Walter R; von Seidlein, Lorenz; Price, Ric N; Barnes, Karen I; Djimdé, Abdoulaye; ter Kuile, Feiko; Gosling, Roly; Chen, Ingrid; Dhorda, Mehul J; Stepniewska, Kasia; Guérin, Philippe; Woodrow, Charles J; Dondorp, Arjen M; Day, Nicholas P; Nosten, Francois H
    Abstract Indirect clinical measures assessing anti-malarial drug transmission-blocking activity in falciparum malaria include measurement of the duration of gametocytaemia, the rate of gametocyte clearance or the area under the gametocytaemia-time curve (AUC). These may provide useful comparative information, but they underestimate dose-response relationships for transmission-blocking activity. Following 8-aminoquinoline administration P. falciparum gametocytes are sterilized within hours, whereas clearance from blood takes days. Gametocytaemia AUC and clearance times are determined predominantly by the more numerous female gametocytes, which are generally less drug sensitive than the minority male gametocytes, whereas transmission-blocking activity and thus infectivity is determined by the more sensitive male forms. In choosing doses of transmission-blocking drugs there is no substitute yet for mosquito-feeding studies.
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    Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa
    (2005) Barnes, Karen I; Durrheim, David N; Little, Francesca; Jackson, Amanda; Mehta, Ushma; Allen, Elizabeth; Dlamini, Sicelo S; Tsoka, Joyce; Bredekamp, Barry; Mthembu, D Jotham; White, Nicholas J; Sharp, Brian L
    Between 1995 and 2000, KwaZulu–Natal province, South Africa, experienced a marked increase in Plasmodium falciparum malaria, fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance. In response, vector control was strengthened and artemether-lumefantrine (AL) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa. In South Africa, effective vector and parasite control had historically ensured low-intensity malaria transmission. Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities.
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    Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures
    (2009) Bicanic, Tihana; Brouwer, Annemarie E; Meintjes, Graeme; Rebe, Kevin; Limmathurotsakul, Direk; Chierakul, Wirongrong; Teparrakkul, Praprit; Loyse, Angela; White, Nicholas J; Wood, Robin; Jaffar, Shabbar; Harrison, Thomas
    Objectives: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune response, and CD4 cell count. Design: Evaluation of 163 HIV-positive ART-naive patients enrolled in three trials of amphotericin B-based therapy for cryptococcal meningitis in Thailand and South Africa. Methods: Study protocols required four lumbar punctures with measurements of opening pressure over the first 2 weeks of treatment and additional lumbar punctures if opening pressure raised. Fungal burden and clearance, CSF immune parameters, CD4 cell count, neurological symptoms and signs, and outcome at 2 and 10 weeks were compared between groups categorized by opening pressure at cryptococcal meningitis diagnosis. Results: Patients with higher baseline fungal burden had higher baseline opening pressure. High fungal burden appeared necessary but not sufficient for development of high pressure. Baseline opening pressure was not associated with CD4 cell count, CSF pro-inflammatory cytokines, or altered mental status. Day 14 opening pressure was associated with day 14 fungal burden. Overall mortality was 12% (20/162) at 2 weeks and 26% (42/160) at 10 weeks, with no significant differences between opening pressure groups. Conclusion: Studies are needed to define factors, in addition to fungal burden, associated with raised opening pressure. Aggressive management of raised opening pressure through repeated CSF drainage appeared to prevent any adverse impact of raised opening pressure on outcome in patients with cryptococcal meningitis. The results support increasing access to manometers in resource-poor settings and routine management of opening pressure in patients with cryptococcal meningitis.