EDCTP-funded projects are addressing diagnosis, treatment and prevention of neglected infectious diseases affecting sub-Saharan Africa.
A parallel session on Thursday morning (9 November) was dedicated to neglected infectious diseases, a wide range parasitic and other infections that cause considerable ill-health but rarely receive the attention they deserve.
Diagnosing visceral leishmaniasis
Visceral leishmaniasis (VL) is a potentially deadly parasitic infection of body tissues. Although diagnostics exist, they have drawbacks, including their safety and accuracy. Working with Dr Dawit Wolday (Mekelle University, Ethiopia), Dr Norbert van Dijk of the Amsterdam University Medical Centre in the Netherlands has found that an innovative new molecular test may provide a better alternative approach to diagnosis.
The group has developed a miniaturised PCR-based test that works directly on blood samples and incorporates an easy-to-read lateral flow immunoassay (dipstick) readout. This dbPCR-NALFIA test, an adapted version of a malaria diagnostic being assessed in an EDCTP trial, is easy to use even in resource-poor settings – it does not require a DNA extraction step, is portable, and utilises a relatively cheap and handheld solar-powered thermal cycler, so no laboratory facilities are needed.
In a laboratory evaluation, Norbert compared the dbPCR-NALFIA test with gold-standard PCR, using a range of stored samples from different countries. The test showed very high sensitivity (86–96%) and specificity (97–100%) and good agreement with PCR results. The next step, he suggested, was now large field evaluation in endemic countries.
Potential applications could include treatment monitoring in VL patients and diagnosis of immunocompromised people, where immunological tests may not perform well.
Treating soil-transmitted helminths
Dr José Munoz, Barcelona Institute for Global Health, Spain, working with colleagues in Ethiopia, Kenya and Mozambique, has been evaluating a refined version of albendazole treatment for soil-transmitted helminths, debilitating parasitic worm infections. Albendazole and similar compounds are widely used but show suboptimal efficacy against some species of worms and there is growing concern about drug resistance.
In a phase II/III trial, part of the EDCTP-funded STOP project, Dr Munoz and his team compared an enhanced form of albendazole treatment that includes ivermectin in a convenient fixed-dose combination (FDC) with the standard albendazole regimen. The phase II part of the trial showed that the FDC was safe in children and adolescents aged 5–17 years, and well-tolerated.
In the phase III study, the FDC showed excellent efficacy, 95% or higher, against Trichuris trichiura (whipworm), hookworm and Strongyloides (threadworm). However, the data for Strongyloides need to be interpreted with caution as the study was underpowered to deliver definitive findings for this parasite.
Through the STOP2030 project, the STOP Consortium has received EDCTP3 funding to take forward the next stage of development of the co-formulation and to prepare for implementation.
Covering the trypanosome family
In 2018, fexinidazole was approved for the treatment of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense, the most common cause of HAT. Dr Olaf Valverde Mordt of the Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland, described how, with colleagues from Malawi and Uganda, fexinidazole has now been shown also to be effective against a second form of HAT, caused by T. brucei rhodesiense (r-HAT).
r-HAT is an acute and potentially lethal condition mainly seen in eastern and southern Africa. Treatment of severe cases has relied on melarsoprol, a toxic arsenic-based drug that kills about 8% of patients it is given to.
A clinical trial in Malawi and Uganda found that fexinidazole was an effective treatment for r-HAT, with no deaths reported during the trial – achieving its primary end goal of non-inferiority to melarsoprol. Following a review of data by the European Medicines Agency (EMA), due to completed by the end of 2023, Olaf hopes that fexinidazole will be available for use against r-HAT in Africa as soon as 2024.
Dr Pytsje Hoekstra, Leiden University Medical Center (Netherlands): Development of a CAA/CCA duplex test for improved diagnosis of human schistosomiasis
Dr Nelly Mwageni, Catholic University of Health and Allied Sciences (Tanzania): Skin diseases and their frequency patterns in skin camps in PEP4LEP implementing districts in Tanzania, preliminary results
Dr Charlie Franck Alfred Compaoré, Institut de Recherche Pour Le Développement (Burkina Faso): Molecular diagnostic tests specificities and their contribution for HAT post-elimination monitoring in Burkina Faso and Côte d’Ivoire