DNDi 15th Anniversary and launch of a special collection on Neglected Diseases and Innovation in South Asia with The BMJ

DNDi celebrated its 15th anniversary and organized a stakeholders meeting at India International Centre, New Delhi in collaboration with Indian Council of Medical Research (ICMR). Prof. Balram Bhargava, Secretary, Department of Health Research & Director General, ICMR, Dr Renu Swarup, Secretary, Department of Bio Technology, GoI, Dr Shekhar C Mande, Secretary, DSIR and Director General, Council of Scientific & Industrial Research, Leena Menghaney, Head, South Asia, MSF Access Campaign were among the participants, as were about 100 DNDi partners, including key policy makers, public and private sector representatives, pharmaceutical industry partners, the Bill and Melinda Gates Foundation, Tata Trust, MSF, and international NGOs. DNDi spoke about the organization’s achievements in the field of neglected diseases and discussed new opportunities for R&D and innovation for neglected patients.

On the occasion, DNDi launched a special collection of articles entitled ‘Neglected Diseases and Innovation in South Asia’ published by The BMJ (formerly The British Medical Journal). The collection brings together over 30 authors from across South Asia and the globe to identify research priorities and recommendations for action to improve the health of neglected patients in the region. The collection maps progress in the control or elimination of neglected diseases such as lymphatic filariasis and kala-azar, examines disease burden and gaps in access to treatment for snakebite envenoming in the region, and highlights the growing challenge of antimicrobial resistance.

The unifying theme of the collection is innovation in diagnostics and treatment, and the need to create solutions for neglected patients that are effective, relevant, locally feasible, and sustainable. India has a unique role to play given its high disease burden and expertise in end-to-end solutions, from drug discovery and clinical studies, through to regulation, manufacture, and distribution. The articles highlight the notable successes of public health programmes in neglected diseases in South Asia and identify areas where research and supportive policy are needed to sustain plans for control or elimination. Authors also called for a comprehensive policy for neglected diseases research in India to foster innovation in drugs, diagnostics, and vaccines, critical to addressing the evolving needs of elimination programmes.

Elimination of vector-borne diseases: current gaps and the need for new tools

DNDi and ICMR-National Institute of Malaria Research, New Delhi, organized a day-long symposium to address different aspects of neglected tropical diseases that have been targeted for elimination – namely lymphatic filariasis, visceral leishmaniasis (VL), and malaria. Experts discussed the gaps in the elimination programme and research for new tools, and identified opportunities to overcome them.   

Though visceral leishmaniasis cases in India have decreased, there is still a need for better tools – e.g., better diagnostics for visceral leishmaniasis relapse and post-kala-azar dermal leishmaniasis (PKDL), and better treatments, including for PKDL and HIV-VL coinfection. Experts recommended the development of algorithms for cost-effective management of febrile illness in endemic regions. It was felt that the definition of death due to visceral leishmaniasis needs to be clearly defined so it can be accurately captured in outcome assessments. There was also agreement on the need to focus on the role of asymptomatic leishmania infection in transmission.

Challenges to lymphatic filariasis elimination include failure of drug dosage and lack of drug monitoring and management of hotspots. A promising new combination therapy for lymphatic filariasis known as IDA that combines a single dose of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) appears to be highly effective, and its safety has been evaluated in large community-based studies in several locations. Morbidity management and disability prevention (MMDP) coverage for lymphatic filariasis needs to reach to 100% of people living in at-risk areas.

In the field of malaria, experts focused on unmet medical needs related to resistance, prevention of relapse, transmission blocking, severe malaria, single-dose cures, and chemoprevention. New treatments to prevent relapse of P. vivax malaria are in development. Discussions were held on the challenges of effective vector control and many novel interventions. A panel discussion on improving surveillance for malaria elimination considered strategies including public-private partnership models.

Hope for new treatment regimen for neglected patients with HIV-VL co-infection in India   

DNDi was a technical partner in an MSF-sponsored study in Bihar state to evaluate treatments with liposomal amphotericin B (LAmB) monotherapy and a combination of LAmB and miltefosine that will provide key evidence to national and regional decision-makers on the best treatment for patients with HIV-VL coinfection. Findings from the study will also inform the national road map for visceral leishmaniasis elimination in India.

Existing treatments for visceral leishmaniasis in HIV co-infected patients are not based on evidence from the region, and more effective treatment regimens are needed. The diagnosis of visceral leishmaniasis is also a challenge in low-income settings where there is a lack of awareness about the disease, poor access to early diagnosis and referral for appropriate treatment and stigma around HIV.

Previous Indian treatment guidelines for visceral leishmaniasis did not differentiate treatment of HIV-VL co-infected patients from that of other patients presenting with visceral leishmaniasis. A total of 150 patients have been enrolled in the study, and the results will be published and presented to the World Health Organization and the Indian government to inform potential policy change.

Clinical trial for PKDL patients in South Asia

A Phase II study of LAmB monotherapy and a combination of LAmB and miltefosine is ongoing in India and Bangladesh to assess safety and efficacy for treating PKDL. This study primarily aims to improve current treatment options for PKDL patients in South Asia.

A total of 126 patients were recruited in the study in India and Bangladesh by the end of 2019. If the proposed regimen proves to be safe and efficacious, it may be possible to provide PKDL patients with shorter-duration treatments, which in turn may increase adherence to treatment.

The results of this trial will be presented to the Kala-azar National Control Programme of the Indian Ministry of Health and could lead to national policy change for PKDL treatment, if supported by the evidence.

The partners in this project in India are Kala Azar Medical Research Centre, Institute of Medical Sciences, Banaras Hindu University, and Rajendra Memorial Research Institute of Medical Sciences, and in Bangladesh, International Centre for Diarrhoeal Disease Research, Dhaka and SK Hospital, Mymensingh.

The Lead Optimisation Consortium in India (LOCI)

With many world-class research institutions and global pharmaceutical organizations, India is rich in both scientific expertise and drug discovery capabilities. To engage with this ecosystem further and to uncover new potential treatments for diseases of significant relevance to India, DNDi has initiated the Lead Optimisation Consortium in India (LOCI) with relevant stakeholders in the country. Initially, partners will work together to discover and optimize new pre-clinical drug candidates for leishmaniasis. With this initiative, we also hope to foster cross-regional and cross-institutional collaboration across the Indian drug discovery ecosystem and deepen our engagement within the country.

LOCI brings together DNDi, IIT Gandhinagar, and the Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management at Narsee Monjee Institute of Management Studies (NMIMS). The collaboration plans to expand to other institutes in India with the purpose of engaging students and young researchers to apply their talents to discovering molecules for potential new treatments for neglected tropical diseases.

Refresher training on revised clinical trial rules in India 

India’s New Drug and Clinical Trials Rules were revised in March 2019. DNDi organized a training for its clinical staff, including Ethics Committee members at the sites where DNDi conducts clinical trials, to apprise them of all the changes. Since its inception in 2003, DNDi has integrated capacity strengthening in all its projects.

The two-day training was organized at Rajendra Prasad Medical Research Institute (RMRI), Patna in September. Around 60 participants from RMRI, Kala Azar Medical Research Centre in Muzaffarpur, MSF, and DNDi attended this training, which was well received. Participants were trained on the revised regulatory framework and requirements for clinical trials in India as per International Conference on Harmonisation Good Clinical Practice (ICH-GCP) and Indian regulations. The new changes bring better clarity, define responsibilities, stress accountability, and harmonize requirements for imports and clinical trials.

Photo credits: Kishore Pandit-DNDi, DNDi, Maneesh Agnihotri-DNDi, Ranjan Rahi