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EDCTP portfolio: Senior Fellowships

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Dr Makhtar Niang is evaluating new diagnostic technology that could make it easier to identify asymptomatic malaria infections.

Identifying hidden malaria infections

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Despite some progress, more than 400,000 people die of malaria every year, the vast majority in sub-Saharan Africa. Nevertheless, with effective drugs and other control measures such as bednets available, the prospect of malaria elimination is increasingly being discussed.

A major obstacle to malaria elimination is likely to be the existence of asymptomatic infections. Parasite numbers may be so low that they do not cause symptoms, but they can still be transmitted via mosquitoes and cause new infections. The other major challenge with asymptomatic infections is that they may be beyond the limits of detection by commonly used rapid diagnostic tests.

The challenge

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In his EDCTP Senior Fellowship, Dr Makhtar Niang aims to test a new, highly sensitive malaria diagnostic suitable for community-based screening. The AnyMDx test detects parasite DNA using ‘loop-mediated isothermal amplification’ (LAMP) technology, which, unlike standard polymerase chain reaction (PCR) approaches, does not require repeated cycles of heating and cooling. It therefore requires less complex equipment and is significantly cheaper.

Dr Niang has spent his research career working on malaria, spending time in laboratories in Europe, the USA and Singapore before returning to Senegal to take up a position at the Institut Pasteur de Dakar. He has made important discoveries about the STEVOR family of proteins, which may play a key role in protecting the parasite from the host immune system.

In Senegal, his work has increasingly focused on low-level and asymptomatic malaria parasite infections. He identified the presence of a less common species of malaria parasite, Plasmodium vivax, in Senegal, and has undertaken an extensive study of asymptomatic infections in two test-bed villages, Dielmo and Ndiop. These studies found significant levels of asymptomatic infections, 7.6% and 9.5% respectively, at the two sites. Importantly, 98% of subsequent infections occurred in households affected by asymptomatic infections.

Dr Niang has already made significant contributions to malaria research, including through his collaborations with researchers in the extensive Institut Pasteur network and beyond. He also co-supervises a PhD student with EDCTP Senior Fellow Professor Faith Osier. Through his Senior Fellowship, he will strengthen his collaborations and undertake training at the Institut Pasteur, Paris, where his mentor, Professor Didier Ménard, is based.

The project

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Dr Niang’s project will provide important data on a diagnostic tool that could play an essential role in malaria elimination, which will depend on the ability to screen populations and identify all residual infections, including asymptomatic ones. His fellowship will also enable Dr Niang to consolidate his reputation in malaria research and nurture additional master’s and PhD students to build malaria research capacity.

Impact

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

Bringing antiretroviral drugs to children

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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

Despite some progress, more than 400,000 people die of malaria every year, the vast majority in sub-Saharan Africa. Nevertheless, with effective drugs and other control measures such as bednets available, the prospect of malaria elimination is increasingly being discussed.

A major obstacle to malaria elimination is likely to be the existence of asymptomatic infections. Parasite numbers may be so low that they do not cause symptoms, but they can still be transmitted via mosquitoes and cause new infections. The other major challenge with asymptomatic infections is that they may be beyond the limits of detection by commonly used rapid diagnostic tests.

watermark

In his EDCTP Senior Fellowship, Dr Makhtar Niang aims to test a new, highly sensitive malaria diagnostic suitable for community-based screening. The AnyMDx test detects parasite DNA using ‘loop-mediated isothermal amplification’ (LAMP) technology, which, unlike standard polymerase chain reaction (PCR) approaches, does not require repeated cycles of heating and cooling. It therefore requires less complex equipment and is significantly cheaper.

Dr Niang has spent his research career working on malaria, spending time in laboratories in Europe, the USA and Singapore before returning to Senegal to take up a position at the Institut Pasteur de Dakar. He has made important discoveries about the STEVOR family of proteins, which may play a key role in protecting the parasite from the host immune system.

In Senegal, his work has increasingly focused on low-level and asymptomatic malaria parasite infections. He identified the presence of a less common species of malaria parasite, Plasmodium vivax, in Senegal, and has undertaken an extensive study of asymptomatic infections in two test-bed villages, Dielmo and Ndiop. These studies found significant levels of asymptomatic infections, 7.6% and 9.5% respectively, at the two sites. Importantly, 98% of subsequent infections occurred in households affected by asymptomatic infections.

Dr Niang has already made significant contributions to malaria research, including through his collaborations with researchers in the extensive Institut Pasteur network and beyond. He also co-supervises a PhD student with EDCTP Senior Fellow Professor Faith Osier. Through his Senior Fellowship, he will strengthen his collaborations and undertake training at the Institut Pasteur, Paris, where his mentor, Professor Didier Ménard, is based.

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.

Dr Niang’s project will provide important data on a diagnostic tool that could play an essential role in malaria elimination, which will depend on the ability to screen populations and identify all residual infections, including asymptomatic ones. His fellowship will also enable Dr Niang to consolidate his reputation in malaria research and nurture additional master’s and PhD students to build malaria research capacity.

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