A5011091618- Malaria Research and Control
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Vaccine Coverage and Hesitancy
- vaccines and immunoinformatics approaches
- Complement system in diseases
- Digital Imaging for Blood Diseases
- Immunotherapy and Immune Responses
- Parasites and Host Interactions
- Immune Cell Function and Interaction
- Ethics in Clinical Research
- Viral gastroenteritis research and epidemiology
- Invertebrate Immune Response Mechanisms
- Hepatitis Viruses Studies and Epidemiology
- Animal Virus Infections Studies
- HIV Research and Treatment
- Escherichia coli research studies
- Global Health and Surgery
- Hepatitis B Virus Studies
- Vector-borne infectious diseases
- Global Maternal and Child Health
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Hemoglobinopathies and Related Disorders
- Disaster Response and Management
Kenya Medical Research Institute
2017-2025
University of Oxford
2015-2025
Angkor Hospital for Children
2017-2025
Wellcome Trust
2018-2024
Swiss Tropical and Public Health Institute
2020
University of Basel
2020
Wellcome Sanger Institute
2020
QIMR Berghofer Medical Research Institute
2019
Ifakara Health Institute
2019
Griffith University
2018
A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment population-wide transmission potential based on 1209 mosquito feeding assays in endemic areas Burkina Faso and Kenya. Across both sites, identified 39 individuals. In high endemicity settings, individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one three lowest setting was detected molecular...
Abstract Malaria infections occurring below the limit of detection standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need be detected targeted achieve malaria elimination. In this study we analyse a range datasets quantify density, detectability, course infection infectiousness subpatent infections. Asymptomatically infected individuals have lower parasite densities on average low...
The standard membrane feeding assay (SMFA) is currently considered to be the 'gold standard' for assessing effectiveness of malaria transmission blocking interventions (TBIs) in vivo. operation and analysis SMFAs has varied between laboratories: field scientists often measure TBI efficacy as a reduction prevalence infected mosquitoes whilst laboratory are more likely quote change number oocysts within mosquito. These metrics give outputs that differ widely, resulting need greater...
High social value is fundamental to justifying these studies
Abstract Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within mosquito, with aim preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering leading candidate antigens, have been developed independently and reported varied activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63 modified vaccinia virus Ankara, MVA, expressing AgAPN1,...
This report of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19 outlines ethical standards challenge studies. It includes eight Key Criteria related to scientific justification, risk-benefit assessment, consultation and engagement, co-ordination research, site selection, participant expert review, informed consent. The document aims provide comprehensive guidance scientists, research ethics committees, funders, policymakers, regulators deliberations regarding...
Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found NK degranulate and release IFN-γ upon stimulation with antibody-opsonized
Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) routinely used to evaluate, prioritize, and quantify the efficacy malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human challenge studies semi-immune volunteers provide an unparalleled opportunity robustly identify mechanistic correlates We leveraged this platform...
Background: The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities capacity development initiatives. However, the ethical issues these studies present LMICs have not been empirically studied. We findings a descriptive social science study nested within malaria study, on-going at time writing, KEMRI-Wellcome Trust Research...
Malaria control strategies need to respond geographical hotspots of transmission. Detection depends on the sensitivity diagnostic tool used. We conducted cross-sectional surveys in 3 sites within Kilifi County, Kenya, that had variable transmission intensities. Rapid test (RDT), microscopy, and polymerase chain reaction (PCR) were used detect asymptomatic parasitemia, detected using spatial scan statistic. Eight thousand five hundred eighty-one study participants surveyed sites. There...
Large-scale surveillance of mosquito populations is crucial to assess the intensity vector-borne disease transmission and impact control interventions. However, there a lack accurate, cost-effective high-throughput tools for mass-screening vectors. A total 750 Anopheles gambiae (Keele strain) mosquitoes were fed Plasmodium falciparum NF54 gametocytes through standard membrane feeding assay (SMFA) afterwards maintained in insectary conditions allow oocyst (8 days) sporozoite development (14...
Many aspects of Controlled Human Infection Models (CHIMs, also known as human challenge studies and infection studies) have been discussed extensively, including Good Manufacturing Practice (GMP) production the agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising incentives, pre-existing immunity, clinical, immunological, microbiological endpoints. The fourth meeting focused on regulation studies, bringing together scientists regulators from high-,...
<ns4:p><ns4:bold>Background:</ns4:bold> The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities capacity development initiatives. However, the ethical issues these studies present LMICs have not been empirically studied. We findings a descriptive social science study nested within malaria study, on-going at time writing,...
<ns4:p>Controlled human infection (CHI) models are gaining recognition as an approach to accelerating vaccine development, for use in both non-endemic and endemic populations: they can facilitate identification of the most promising candidate vaccines further trials advance understanding protective immunity. Helminths present a continuing health burden sub-Saharan Africa. Vaccine development these complex organisms is particularly challenging, partly because responses akin mechanisms...
Abstract First‐generation, E1/E3‐deleted adenoviral vectors with diverse transgenes are produced routinely in laboratories worldwide for development of novel prophylactics and therapies a variety applications, including candidate vaccines against important infectious diseases, such as HIV/AIDS, tuberculosis, malaria. Here, we show, two different (both encoding malarial antigens) inserted at the E1 locus, that rare viruses containing transgene‐inactivating mutation exhibit selective growth...
A malaria transmission-blocking vaccine would be a critical tool in achieving elimination and eradication. Using chimpanzee adenovirus serotype 63 modified vaccinia virus Ankara viral vectored vaccines, we investigated whether incorporating two antigens into one result higher transmission-reducing activity than antigen. We demonstrated that when Pfs25 was administered with other Pfs28 or Pfs230C, either concurrently, as mixed vaccine, co-expressed dual-antigen the antibody response mice to...
<ns4:p>Malaria remains a major public health burden despite approval for implementation of partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development more multi-stage Adults in endemic areas may have substantial immunity provided by responses the blood stages parasites, but field trials conducted on several blood-stage vaccines not shown high levels efficacy. We will use controlled human infection (CHMI) models with malaria-exposed volunteers...
<ns4:p>Malaria remains a major public health burden despite approval for implementation of partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development more multi-stage Adults in endemic areas may have substantial immunity provided by responses the blood stages parasites, but field trials conducted on several blood-stage vaccines not shown high levels efficacy. We will use controlled human infection (CHMI) studies with malaria-exposed volunteers...
Abstract Ring-infected erythrocytes are the predominant asexual stage in peripheral circulation but rarely investigated context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis ring-infected parasite cultures samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below predefined threshold 500 parasites/μl and were treated until end...
Abstract Background Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought assess the controlled human infection (CHMI) model as a means of studying naturally acquired Kenyan adults with varying Methods analysed data from 142 three locations representing distinct endemicity (Ahero, Kilifi North and South) enrolled CHMI study Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify vivo outcomes that most...
Shigella is associated with a significant burden of disease worldwide among individuals all ages and the major cause moderate severe diarrhea in children under five years age low- middle-income countries. Several candidate vaccines against species are currently clinical development. The investigational 1790GAHB vaccine sonnei based on GMMA (Generalized Modules for Membrane Antigens) technology. was well tolerated induced high antibody levels early-phase trials both -endemic non-endemic...
Background Controlled human malaria infection (CHMI) studies are considered a powerful tool for assessing the efficacy of vaccines and investigating immunity against infection. The monitoring has historically been carried out by microscopy and/or more recently sensitive quantitative polymerase chain reaction (qPCR) based on 18S ribosomal RNA (rRNA) gene. Here we describe validation molecular assay previously developed to quantify parasites in CHMI. Methods We used primers probes rRNA...
ABSTRACT Shigella is a leading cause of diarrheal morbidity and mortality in young children from low- middle-income countries. Here, we aimed to verify the ability generalized modules for membrane antigens (GMMA)-based sonnei candidate vaccine 1790GAHB elicit an anti-protein antibody response. Serum samples previous clinical trials adults (a dose-escalation study its extension France, efficacy after human challenge United States, Kenya) were investigated using pan-proteome microarrays...
Reducing malaria transmission has been a major pillar of control programmes and is considered crucial for achieving elimination. Gametocytes, the transmissible forms P. falciparum parasite, arise during blood stage parasite develop through 5 morphologically distinct stages. Immature gametocytes (stage I-IV) sequester in extravascular niche bone marrow possibly spleen. Only mature V re-enter peripheral circulation to be taken up by mosquitoes successful onward transmission. We have recently...