Browsing by Author "Lowe B"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Clinical laboratory reference values amongst children aged 4 weeks to 17 months in Kilifi, Kenya: A cross sectional observational study.
    (2017) Gitaka J; Ogwang C; Ngari M; Akoo P; Olotu A; Kerubo C; Fegan G; Njuguna P; Nyakaya G; Otieno T; Mwambingu G; Awuondo K; Lowe B; Chilengi R; Berkley JA; Clinical Trials Facility, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya.; The Childhood Acute Illness & Nutrition Network (CHAIN), Nairobi, Kenya.; Department of Clinical Medicine, School of Health Sciences, Mount Kenya University, Thika, Kenya.; Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, United Kingdom.; Swansea Trials Unit, Swansea University Medical School, Swansea University, Swansea, United Kingdom.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Reference intervals for clinical laboratory parameters are important for assessing eligibility, toxicity grading and management of adverse events in clinical trials. Nonetheless, haematological and biochemical parameters used for clinical trials in sub-Saharan Africa are typically derived from industrialized countries, or from WHO references that are not region-specific. We set out to establish community reference values for haematological and biochemical parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We conducted a cross sectional study nested within phase II and III trials of RTS, S malaria vaccine candidate. We analysed 10 haematological and 2 biochemical parameters from 1,070 and 423 community children without illness prior to experimental vaccine administration. Statistical analysis followed Clinical and Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and their respective 90% confidence intervals were determined using non-parametric methods. Findings were compared with published ranges from Tanzania, Europe and The United States. We determined the reference ranges within the following age partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months to 17 months for the haematological parameters; and 4 weeks to 17 months for the biochemical parameters. There were no gender differences for all haematological and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference ranges in infants largely overlapped with those from United States or Europe, except for the lower limit for Hb, Hct and platelets (lower); and upper limit for platelets (higher) and haematocrit(lower). Community norms for common haematological and biochemical parameters differ from developed countries. This reaffirms the need in clinical trials for locally derived reference values to detect deviation from what is usual in typical children in low and middle income countries.
  • Thumbnail Image
    Item
    Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.
    (2015-Apr-28) Hodgson SH; Juma E; Salim A; Magiri C; Njenga D; Molyneux S; Njuguna P; Awuondo K; Lowe B; Billingsley PF; Cole AO; Ogwang C; Osier F; Chilengi R; Hoffman SL; Draper SJ; Ogutu B; Marsh K; Sanaria Inc, Rockville, MD, USA. pbillingsley@sanaria.com.; Sanaria Inc, Rockville, MD, USA. shoffman@sanaria.com.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. smolyneux@kemri-wellcome.org.; The Jenner Institute, University of Oxford, Oxford, UK. Susanne.hodgson@ndm.ox.ac.uk.; Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. omandi.cole@gmail.com.; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. danielnjengah@yahoo.com.; Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. eajuma@kemri.org.; Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. bernhards.ogutu@indepth-network.org.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. asalim@kemri-wellcome.org.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. fosier@kemri-wellcome.org.; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. eajuma@kemri.org.; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. charles.magiri@usamru-k.org.; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. omandi.cole@gmail.com.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. patwnju@yahoo.co.uk.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. blowe@kemri-wellcome.org.; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. bernhards.ogutu@indepth-network.org.; The Jenner Institute, University of Oxford, Oxford, UK. simon.draper@ndm.ox.ac.uk.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Roma.Chilengi@cidrz.org.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. kevin.marsh@ndm.ox.ac.uk.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. kawuondo@kemri-wellcome.org.; Kenya Medical Research Institute - Wellcome Trust, Centre for Geographical Medical Research (Coast), Kilifi, Kenya. COgwang@kemri-wellcome.org.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries. METHODS: An open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa. DISCUSSION: This paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested. CONCLUSIONS: Performing CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.