Dr Charles Sande

Kenya

EDCTP portfolio: Career Development Fellowships

Dr Charles Sande will contribute to developing new diagnostics for pneumonia, which would enable appropriate use of antibiotics and reduce risks of spreading AMR.

Biomarkers of acute pneumonia in children

Over 90% of the mortality attributed to pneumonia infection occurs in developing countries and pneumonia is second only to malaria as a cause of infant and early childhood mortality in sub-Saharan Africa.

The treatment of pneumonia depends on whether its aetiology is viral or bacterial. Care of most viral pneumonia infections is restricted to symptomatic management. On the other hand, antibiotics are an effective way of treating bacterial pneumonia and timely administration of antimicrobial therapy usually has a positive clinical outcome. In developed countries, these infections are often diagnosed using sophisticated platforms. However, these platforms are generally unavailable in typical health facilities in low-resource countries, where the toll of pneumonia infection is greatest.

The lack of these diagnostic platforms means that clinicians in these settings do not have sufficient clinical information to determine whether antibiotic treatment is appropriate. This has led to the widespread presumptive use of antibiotics as empiric treatment for pneumonia, Antibiotics are being administered to vast numbers of children with viral pneumonia who do not need them. This overuse of antibiotics has been implicated in the alarming spread of antimicrobial resistance (AMR), which is estimated to be the leading cause of paediatric death by 2050 if corrective measures are not devised.

The challenge

To address this problem, Dr Sande aims to validate host-level biomarkers that can rapidly and reliably distinguish viral and bacterial pneumonia and that be formulated into a rapid point-of-care test. In a previous study of airway proteomics, 15 host proteins were identified that could distinguish with high sensitivity and specificity between viral and bacterial pneumonia in African children.

In his fellowship study, Dr Sande proposes to validate the results from the previous study. He will use an independent retrospective cohort of infants and children who were previously admitted to a hospital with severe pneumonia and whose airway samples were archived in a biobank. By measuring the expression levels of the candidate biomarker proteins in these samples, it is hoped to select the three that are most discriminative of pneumonia aetiology for further testing in a prospective cohort.

The project

If successful, the results of this study will contribute to the fight against AMR by providing clinicians with a robust tool for guiding decisions to administer antibiotics, specifically in cases of acute pneumonia in children.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Over 90% of the mortality attributed to pneumonia infection occurs in developing countries and pneumonia is second only to malaria as a cause of infant and early childhood mortality in sub-Saharan Africa.

The treatment of pneumonia depends on whether its aetiology is viral or bacterial. Care of most viral pneumonia infections is restricted to symptomatic management. On the other hand, antibiotics are an effective way of treating bacterial pneumonia and timely administration of antimicrobial therapy usually has a positive clinical outcome. In developed countries, these infections are often diagnosed using sophisticated platforms. However, these platforms are generally unavailable in typical health facilities in low-resource countries, where the toll of pneumonia infection is greatest.

The lack of these diagnostic platforms means that clinicians in these settings do not have sufficient clinical information to determine whether antibiotic treatment is appropriate. This has led to the widespread presumptive use of antibiotics as empiric treatment for pneumonia, Antibiotics are being administered to vast numbers of children with viral pneumonia who do not need them. This overuse of antibiotics has been implicated in the alarming spread of antimicrobial resistance (AMR), which is estimated to be the leading cause of paediatric death by 2050 if corrective measures are not devised.

To address this problem, Dr Sande aims to validate host-level biomarkers that can rapidly and reliably distinguish viral and bacterial pneumonia and that be formulated into a rapid point-of-care test. In a previous study of airway proteomics, 15 host proteins were identified that could distinguish with high sensitivity and specificity between viral and bacterial pneumonia in African children.

In his fellowship study, Dr Sande proposes to validate the results from the previous study. He will use an independent retrospective cohort of infants and children who were previously admitted to a hospital with severe pneumonia and whose airway samples were archived in a biobank. By measuring the expression levels of the candidate biomarker proteins in these samples, it is hoped to select the three that are most discriminative of pneumonia aetiology for further testing in a prospective cohort.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

If successful, the results of this study will contribute to the fight against AMR by providing clinicians with a robust tool for guiding decisions to administer antibiotics, specifically in cases of acute pneumonia in children.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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