Happy New Year from the DOLF Team! DOLF has been hard at work at our clinical trial sites and in the lab, and we are pleased to share a summary of our accomplishments of the past year.
Research Updates
Côte d’Ivoire (CDI)
2024 has been productive for DOLF projects in Côte d’Ivoire with completion of two important collaborative clinical trials and initiation of a new spin-off study.
Moxidectin combination therapies for Lymphatic Filariasis (LF). This three-year clinical trial wrapped up the last follow-up visits in July. We are grateful for our partnership with the Swiss Center for Scientific Research in Côte d’Ivoire (Centre Suisse de Recherches Scientifique en Côte d’Ivoire, CSRS), which conducted the work, and with Medicines Development for Global Health (MDGH), who donated moxidectin for the study. This study showed that moxidectin plus albendazole (MoxA) is much more effective than ivermectin plus albendazole (IA, the currently recommended mass treatment regimen for LF elimination programs in Africa). A manuscript reporting these results has been submitted for publication. In November, DOLF investigators Dr. Benjamin Koudou (CSRS), Dr. Catherine Bjerum (Case Western Reserve University) and Dr. Philip Budge (WashU) shared results of the study with government health officials and other stakeholders including community leaders and study participants in Agboville, Côte d’Ivoire (see photo).
MDGH-Mox-3002 in CDI. This large community study examines the safety of moxidectin plus albendazole in an area that is co-endemic for LF and onchocerciasis (river blindness). The study was sponsored by MDGH and was conducted by CSRS with technical assistance from DOLF. Over 850 children 4 to 11 years of age were enrolled and safety data were collected through three months post-treatment. Data from the study will help determine whether MoxA is safe for use as a regimen for mass drug administration for elimination of LF and onchocerciasis in Africa. Results from this study will be part of a dossier that will be considered by WHO.
Efficacy follow-up of MDGH-Mox-3002 participants. Many of the individuals treated in the MGDG-Mox-3002 study were found to be infected with microfilariae (larval worms) in blood (LF) or skin (onchocerciasis). In a DOLF-sponsored study and in collaboration with MDGH, CSRS will follow these infected individuals for two years post-treatment to compare the efficacy of MoxA vs. IA. Early results will be available in 2025, and final results will be available in 2026.
Liberia
Preparing to initiate the clinical trial at Bong-Mine Hospital in Bong Mines, Liberia (70 miles from the capital city Monrovia), proved to be an exciting and challenging task. In February 2024, Kurt Curtis and Kerstin Fischer travelled to Bong Mines to help set up the site with ophthalmology equipment and to begin training the laboratory team. Dr. Peter Fischer, Dr. Adebiyi Adeniran, and Lexi Dyer arrived a few weeks later to continue the general training for clinical trials and data management while the study ophthalmology consultant, Dr. Eric Kanza, traveled from the Democratic Republic of the Congo (DRC) to deliver the ophthalmology training and eye exam standardization. Site monitors from Ghana, Michael Ntiri and Margaret Williams, advised on regulatory requirements. The first study participants were enrolled on April 8 and since then, 286 participants in 20 cohorts were examined and treated once. Most participants received 3-month follow up visits in their village and 48 participants have received a follow-up exam and second treatment at 6 months in the hospital. Only mild or moderate adverse events were observed, and no treatment-associated serious adverse events were recorded. Despite extensive monitoring for adverse events in the eye, no ocular adverse events were noticed. The study has proceeded well, and preliminary safety results were reported in a latebreaker poster at the annual meeting of the ASTMH in New Orleans (see below for more details).
The study site at Bong Mines Hospital was completed in time for study initiation. The renovated rooms for the study participants have separate washrooms, and air conditioners were installed in the examination rooms and the main hall of the hospital ward. Wi-Fi was set up for the entire ward and the project offices. In July we added solar power systems to the hospital and the guesthouse to help reduce energy costs and reduce dependency on the availability of generator fuel. With this addition, 24-hour electricity is supplied to the entire hospital and the guest house. The guest house hosted many international project guests, and it was exciting to see the progress and improvements to the study infrastructure throughout the year. Visitors from WashU during the last year included Dr. Adebiyi Adeniran, Kurt Curtis, Lexi Dyer, Nicole Fetcho, Kerstin Fischer, Dr. Peter Fischer, Jennifer Klenke, Laura Peer and Dr. Gary Weil.
Indonesia
2024 was a busy year for field work in Belitung District, Indonesia, and for laboratory work at Universitas Indonesia in Jakarta. In Belitung District, Professor Tania Supali’s team screened almost 4,000 people in 13 villages for worm larvae. Despite two effective rounds of ivermectin plus DEC and albendazole (IDA) mass drug administration, more than 40 individuals infected with Brugia malayi, worm larvae transmitted through mosquitoes, were found. Although infected individuals mostly cleared worm larvae after treatment, new positive cases were continuously discovered. Together with WashU’s Makedonka Mitreva and her computational biology group, our population genomic work showed that parasites in humans and in animals (monkeys) belong to the same population. An exchange of B. malayi parasites between animals and humans is possible, if both are bitten by the same mosquito vectors.
In December, DOLF Postdoc Dr. Irina Diekmann traveled to Jakarta and helped screen thousands of potential mosquito vectors for filarial DNA using previously standardized assays. Overall, this study generated large data sets on compliance to intervention, and on the B. malayi infection rate in humans, animals and vectors. We are close to completing this puzzle and answering the question of how to eliminate lymphatic filariasis caused by zoophilic B. malayi.
Papua New Guinea (PNG)
Long-term impact of mass drug administration (MDA) with IDA on lymphatic filariasis in Bogia District (north coast of the PNG mainland). Prior studies showed that two rounds of MDA with IDA (ivermectin plus DEC and albendazole) had a huge impact on reducing W. bancrofti prevalence in Bogia Distric, PNG. Studies in progress are looking at the long-term outcome of IDA in that area with a focus on molecular xenomonitoring (detection of filarial DNA in mosquitoes), which is very sensitive for detecting LF persistence in low prevalence areas.
IDA roll-out in East New Britain (an island province in PNG with a population of >300,000). Surveys conducted before and after two rounds of MDA with IDA with high coverage show that W. bancrofti microfilaria prevalence has been reduced to less than 1% in almost all areas surveyed. Mop-up operations are needed for remaining hotspots. Cohort studies showed that IDA works very well in this region; those results suggest that LF persistence in areas with high baseline prevalence is due to incomplete MDA compliance. These studies also showed the superiority of model-based geostatistical sampling (MBGS) over population proportional sampling (PPS) for identifying areas at high risk for LF persistence after MDA. Studies in progress are using molecular xenomonitoring as a supplemental sampling strategy to document interruption of transmission following MDA. Dr. Christopher King (Case Western Reserve University) and colleagues are working with health authorities in PNG to use lessons from the ENB project to form a comprehensive monitoring and evaluation strategy for the government’s planned phased roll-out of IDA in the 12 remaining LF endemic provinces in the country.
Diagnostic/Biomarker Development
The Gates Foundation supported our efforts to develop novel diagnostics for filarial infections and this has led to some new discoveries. Dr. Sarah Greene developed an antigen ELISA that correlates with high parasite densities of L. loa. A similar test using a different target molecule was independently developed by Dr. Philip Budge. Dr. Lucia Sanchez di Maggio and Kerstin Fischer developed a strategy to assess the protein inventory of worm tissue in histological sections by combining laser capture micro dissection and mass spectrometry. The assay development for antigen tests for onchocerciasis and lymphatic filariasis has advanced and resulted in many promising targets. Because of these accomplishments, the group received a supplement from the Gates Foundation to outsource generation of monoclonal antibodies, which is now in progress.
International Meetings and Other Projects
Dr. Peter Fischer attended major international meetings on diagnostics of filarial infections in two European capital cities. The COR-NTD-supported meeting in Paris focused on the development and implementation of diagnostics for loiasis to support elimination of onchocerciasis and lymphatic filariasis in Central Africa. In London, a meeting brought together NTD specialists to support xenomonitoring of lymphatic filariasis for post-elimination surveillance.
Kerstin Fischer continued her collaboration with the University of Bonn on machine learning for histology of Onchocerca nodules and helped to assess Onchocerca volvulus nodules after treatment with the new drug emodepside for the organization Drugs for Neglected Diseases initiative (DNDi). Furthermore, the DOLF management team started the preparation of DOLF’s 15th Anniversary Symposium to be held from April 30 to May 2, 2025, in St. Louis, USA.
ASTMH Annual Meeting in New Orleans
The 2024 Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) was held in New Orleans, and the DOLF team was well represented. We kicked off the conference week with the DOLF Update Meeting and Investigators Meeting. Thirty of DOLF’s implementing, collaborating, and funding partners gathered to provide updates on the clinical trials and biomarker work across our global sites, and to lay the framework for future collaborations. At the ASTMH Annual Meeting, many DOLF team members presented and facilitated panels. Dr. Gary Weil participated in the panel The Role of Molecular Xenomonitoring in Transmission Risk Assessment and Post-Validation Surveillance After Mass Drug Administration for Lymphatic Filariasis; Dr. Philip Budge co-chaired the Filariasis – Epidemiology and Control session, and co-directed the symposium, Evaluating the Case for Loiasis as a Neglected Tropical Disease. Dr. Irina Diekmann and Dr. Sarah Greene, as well as DOLF implementing partners Dr. Tania Supali and Dr. Benjamin Koudou, presented on panels. Kurt Curtis, Dr. Irina Diekmann, Lexi Dyer, Kerstin Fischer, and Dr. Lucia Sanchez Di Maggio each presented scientific posters. We were proud to celebrate Dr. Irina Diekmann, who received the Honorable Mention for the Young Investigators Award for her research on lymphatic filariasis in macaques and other mammals in Indonesia, and what this might mean for LF elimination.
New Team Members
This year, DOLF welcomed three news team members: Abakar Gankpala, Research Technician; Kassandra Huneycutt, Research Administrator; and Laura Peer, Associate Director.
Publications
Five manuscripts reporting DOLF-sponsored research were published this year, with one in press, and many more in progress for publication in 2025. For the complete list of DOLF-sponsored publications, visit https://dolfproject.wustl.edu/publications/.
Leadership Changes at DOLF
DOLF’s founding Principal Investigator, Dr. Gary Weil, has announced his plan to retire at the end of the 2024-2025 academic year. He has transitioned to the role of Senior Advisor and will remained linked to the project as an emeritus professor. Dr. Peter Fischer has taken on the leadership role of DOLF Principal Investigator, and Dr. Philip Budge is the Director of Clinical Research. This new leadership structure is in place and will seamlessly lead the DOLF Project to continue and grow our work to end neglected tropical diseases into the future. We are grateful to Dr. Weil for his vision and leadership, and we look forward to celebrating his accomplishments in spring 2025. We will provide more details in early 2025.
Save the Date!
Please mark your calendar for DOLF’s 15th Anniversary Symposium at Washington University in St. Louis, USA, April 30-May 2, 2025. Keep an eye on our event page for more details to come soon!
The DOLF team wishes you the best in 2025!
| The DOLF Project’s work is supported by the Gates Foundation and the Barnes Jewish Hospital Foundation. |