Browsing by Author "Kapulu M"

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Anti-microbial peptide gene expression during oral vaccination: analysis of a randomized controlled trial.
(2016-Nov) Simuyandi M; Kapulu M; Kelly P; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. m.p.kelly@qmul.ac.uk.; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.; Programme for the Awareness and Elimination of Diarrhoea (PAED), Centre for Infectious Disease Research in Zambia.; Barts and the London School of Medicine, London, UK. m.p.kelly@qmul.ac.uk.; Biological Sciences Department, School of Natural Sciences, University of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
We have observed previously that micronutrient supplementation ameliorated suppression of α-defensin expression during diarrhoea. However, how interactions between anti-microbial peptide (AMP) expression and diarrhoeal disease are altered by micronutrient supplementation remain unclear. Using oral vaccination as a model of intestinal infection, we measured changes in AMP expression during multiple micronutrient supplementation. In the first part, volunteers underwent duodenal jejunal biopsy before and at 1, 2, 4 or 7 days after administration of one of three live, attenuated oral vaccines against rotavirus, typhoid and enterotoxigenic Escherichia coli. In the second part, participants were randomized to receive a multiple micronutrient supplement or placebo for 6 weeks before undergoing intestinal biopsy, vaccination against typhoid and rebiopsy after 14 days. Expression of human alpha-defensin (HD)5, HD6, hBD1, hBD2 and LL-37 was measured by quantitative reverse transcription-polymerase chain reaction. Taken together, the bacterial vaccines, but not rotavirus vaccine, reduced HD5 expression (P = 0·02, signed-rank test) and reduced LL-37 expression in seven of the eight individuals whose biopsies had expression prevaccination (P = 0·03). hBD2 was not detected. In the controlled trial, HD5 and HD6 expression after vaccination was lower [median ratio 0·5, interquartile range (IQR) = 0·07-2·2 and 0·58, IQR = 0·13-2·3, respectively] than before vaccination. There was no significant effect detected of micronutrient supplementation on expression of HD5, HD6, hBD1 or LL-37. We conclude that live attenuated bacterial vaccines, but not rotavirus vaccine, can reduce intestinal α-defensins, and typhoid vaccine reduced LL-37 expression. We found no evidence that micronutrient supplementation in the short term had any impact on anti-microbial peptide expression.
Engagement of ethics and regulatory authorities on human infection studies: Proceedings of an engagement workshop in Zambia.
(2021) Kunda-Ng'andu EM; Simuyandi M; Kapulu M; Chirwa-Chobe M; Mwanyungwi-Chinganya H; Mwale S; Chilengi R; Sharma A; Research Department, The centre for Infectious Disease Research in Zambia, Lusaka, Zambia, 10101, Zambia.; Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.; Biosciences, KEMRI-Wellcome trust research Programme, Kilifi, Kenya.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Human infection studies (HIS) have generally been used as a tool in the pathway for vaccine development in high income settings. Over the last decade, this model has been implemented in LMICs with the aim of accelerating development of next generation vaccines that would perform better in these settings. However, in most LMICs, the ethics and regulatory framework for the conduct of these studies are not in place. In Zambia, these studies are yet to be conducted and thus we conducted a stakeholder engagement workshop in October 2019. We engaged with bioethicists, regulatory authority officials, and scientists from within Zambia and other African countries to anticipate and address foreseeable ethical and regulatory issues when conducting HIS in Zambia for the first time. The workshop largely focused on sensitizing the stakeholders on the benefits of these studies with the following main points for consideration on the implementation of these studies in Zambia: need for in-country legal framework and guidelines; need for adequate informed consent based on comprehensive understanding of the concept of HIS and study requirements; and requirements for heightened vigilance to assure participant safety including good ethical and clinical practice with regulatory, ethical, data safety, and community oversight. Additionally, the workshop emphasized the need for rigorous health screening prior to enrolment; suitable infrastructure for containment; and personnel to provide appropriate treatment including emergency resuscitation and evacuation if indicated. Specific recommendations included compensation for burden of participation; access to care and provision for study related injury (e.g. no-fault insurance); and withdrawal and exit procedures to preserve individual and community safety. Finally, the meeting concluded that researchers should actively engage key gate keepers including civic leaders such as parliamentarians, universities, researchers, potential participants and laypersons to avoid circulation of misinformation.
Fourth Controlled Human Infection Model (CHIM) meeting, CHIM regulatory issues, May 24, 2023.
(2024-Feb) Cavaleri M; Kaslow D; Boateng E; Chen WH; Chiu C; Choy RKM; Correa-Oliveira R; Durbin A; Egesa M; Gibani M; Kapulu M; Katindi M; Olotu A; Pongsuwan P; Simuyandi M; Speder B; Talaat KR; Weller C; Wills B; Baay M; Balasingam S; Olesen OF; Neels P; MRC/UVRI and LSHTM Uganda Research Unit, Uganda; London School of Hygiene and Tropical Medicine, UK. Electronic address: Moses.Egesa@mrcuganda.org.; IABS-EU, Lyon, France. Electronic address: pieter.neels@vaccine-advice.be.; Imperial College London, UK. Electronic address: m.gibani@imperial.ac.uk.; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam. Electronic address: bwills@oucru.org.; Katindi & Company, Kenya. Electronic address: mkatindi@katindilawyers.co.ke.; KEMRI-Wellcome Trust Research Programme, Kenya. Electronic address: mkapulu@kemri-wellcome.org.; Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Electronic address: adurbin1@jhu.edu.; Fundação Oswaldo Cruz (Fiocruz), Brazil.; Food and Drugs Authority, Ghana. Electronic address: gus4tee@gmail.com.; Wellcome Trust, London, UK. Electronic address: shobana.balasingam@wellcome.org.; Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Electronic address: ktalaat@jhu.edu.; US Food & Drugs Administration, USA. Electronic address: david.kaslow@fda.hhs.gov.; Centre for Infectious Disease Research, Zambia. Electronic address: Michelo.Simuyandi@cidrz.org.; European Vaccine Initiative, Heidelberg, Germany. Electronic address: ole.olesen@euvaccine.eu.; Wellcome Trust, London, UK. Electronic address: C.Weller@wellcome.org.; Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.; European Medicines Agency, Netherlands. Electronic address: marco.cavaleri@ema.europa.eu.; Ifakara Health Institute, Tanzania. Electronic address: aolotu@ihi.or.tz.; HVIVO plc, UK. Electronic address: b.speder@hvivo.com.; Center for Vaccine Development, University of Maryland School of Medicine, USA. Electronic address: wilbur.chen@som.umaryland.edu.; Imperial College London, UK. Electronic address: c.chiu@imperial.ac.uk.; P95 Epidemiology & Pharmacovigilance, Leuven, Belgium. Electronic address: marc.baay@p-95.com.; PATH Center for Vaccine Innovation and Access, Seattle, WA, USA. Electronic address: rchoy@path.org.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Many aspects of Controlled Human Infection Models (CHIMs, also known as human challenge studies and human infection studies) have been discussed extensively, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on regulation of CHIM studies, bringing together scientists and regulators from high-, middle-, and low-income countries, to discuss barriers and hurdles in CHIM regulation. Valuable initiatives for regulation of CHIMs have already been undertaken but further capacity building remains essential. The Wellcome Considerations document is a good starting point for further discussions.