Dr Alexander Kwarteng

Ghana

EDCTP portfolio: Career Development Fellowships

Dr Alexander Kwarteng aims to identify the bacteria that likely aggravate the condition of patients suffering from lymphoedema due to lymphatic filariasis.

Impact of secondary bacterial infection on filarial lymphoedema

Filarial infections affect more than 150 million people in the tropics. One of the major forms is lymphoedema caused by Wuchereria bancrofti in Africa. The chronicity and morbidity of lymphatic filariasis (LF) are associated with the longevity of the adult worm (>5 years) and the production of millions of microfilariae, which populate the blood. Existing WHO control programmes rely on mass administration of mainly microfilaricidal drugs (MDA) that have the potential to reduce microfilariae loads in infected humans and, thus, transmission by the insect vector.

Several challenges, however, may impede sustainable control and there have been calls to search for an alternative and effective approach to understanding the pathogenesis of lymphoedema and offering a possible option of providing support for individuals with this stage of lymphatic filariasis.

The challenge

Dr Kwarteng’s project will address lymphoedema caused by Wuchereria bancrofti. Morbidity is imposed not by microfilariae, but by adult worms that induce an alteration of the lymphatic vessels where they reside, causing both vessel obstruction and dilatation. This results in lymphatic pathology, with two manifestations being hydrocele and lymphoedema. Furthermore, exogenous bacteria that enter through skin lesions are believed to aggravate lymphoedema through secondary infections.

Therefore, Dr Kwarteng hypothesises that exogenous bacteria are major mediators of lymphedema and that this could lead to complementary chemotherapy approaches against lymphatic filariasis. This is very important as current WHO control programmes can target transmission with the existing microfilaricidal drugs, but morbidity from lymphoedema and hydrocele (from which more than 40 million people suffer), cannot be sufficiently addressed by antifilarial chemotherapy. Moreover, the bacteria which are believed to contribute to lymphoedema progression in Ghana remain to be studied.

The project

Africa bears one-third of the lymphatic filariasis cases. Current chemotherapy used for mass drug administration programmes (diethylcarbamazine, ivermectin and albendazole), shows no or only partial macrofilaricidal effect. Therefore, it is not able to target the adult worms. The results of this project potentially will have a great impact on the possibilities to support patients suffering from lymphoedema.

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

Filarial infections affect more than 150 million people in the tropics. One of the major forms is lymphoedema caused by Wuchereria bancrofti in Africa. The chronicity and morbidity of lymphatic filariasis (LF) are associated with the longevity of the adult worm (>5 years) and the production of millions of microfilariae, which populate the blood. Existing WHO control programmes rely on mass administration of mainly microfilaricidal drugs (MDA) that have the potential to reduce microfilariae loads in infected humans and, thus, transmission by the insect vector.

Several challenges, however, may impede sustainable control and there have been calls to search for an alternative and effective approach to understanding the pathogenesis of lymphoedema and offering a possible option of providing support for individuals with this stage of lymphatic filariasis.

Dr Kwarteng’s project will address lymphoedema caused by Wuchereria bancrofti. Morbidity is imposed not by microfilariae, but by adult worms that induce an alteration of the lymphatic vessels where they reside, causing both vessel obstruction and dilatation. This results in lymphatic pathology, with two manifestations being hydrocele and lymphoedema. Furthermore, exogenous bacteria that enter through skin lesions are believed to aggravate lymphoedema through secondary infections.

Therefore, Dr Kwarteng hypothesises that exogenous bacteria are major mediators of lymphedema and that this could lead to complementary chemotherapy approaches against lymphatic filariasis. This is very important as current WHO control programmes can target transmission with the existing microfilaricidal drugs, but morbidity from lymphoedema and hydrocele (from which more than 40 million people suffer), cannot be sufficiently addressed by antifilarial chemotherapy. Moreover, the bacteria which are believed to contribute to lymphoedema progression in Ghana remain to be studied.

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.

Africa bears one-third of the lymphatic filariasis cases. Current chemotherapy used for mass drug administration programmes (diethylcarbamazine, ivermectin and albendazole), shows no or only partial macrofilaricidal effect. Therefore, it is not able to target the adult worms. The results of this project potentially will have a great impact on the possibilities to support patients suffering from lymphoedema.

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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