IMMRSE-U: Implementing Malaria MoleculaR SurveillancE in Uganda

The Bill & Melinda Gates Foundation has funded a new project, IMMRSE-U: Implementing Malaria MoleculaR SurveillancE in Uganda, an ambitious addition of genomic epidemiology to standard malaria surveillance. Dr. Jessica Briggs, Dr. Melissa Conrad, Dr. Bryan Greenhouse and Dr. Phil Rosenthal will be working with Drs. Isaac Ssewanywana and Sam Nsobya at IDRC (Infectious Diseases Research Collaboration), the Uganda Ministry of Health, and the African Center of Excellence in Bioinformatics to integrate malaria genomics into routine surveillance activities in Uganda. 

Uganda malaria reference center map

The grant will expand the use of genomic epidemiology to address malaria caused by P. falciparum in one of the highest burden areas of the world.  Building on UCSF’s extensive 20 year collaboration with IDRC, the award will fund sample collection from a network of 70 health facilities -the Uganda Malaria Surveillance Project (UMSP) -- and establish a state-of-the-art genomics facility at the Central Public Health Laboratory in Butabika, Uganda. Dr Briggs and the UCSF team will support our partner’s efforts to integrate genomic data by providing training and mentorship at UCSF and across our partner sites. The experience gained will inform the development of best practices for high burden areas, to create actionable, impactful information for use by the Ministry of Health and National Malaria Control Division. 

The technology to sequence parasite DNA has become less and less expensive, while the amount of blood needed for high quality sequencing results has become smaller and smaller. This study will use a technique called highly multiplex amplicon deep sequencing to pull out short sequences of important sections of the parasite genome, using only a dried blood spot as starting material. These sequences, or “amplicons,” allow us to genotype only the parts of the genome that contain useful information, e.g. sequences that confer antimalarial or diagnostic resistance, or are highly diverse and provide information about the parasite population. This allows our team to save money and computational power when compared to techniques like whole genome sequencing, while providing more sensitive detection of malaria parasites present in infections. The development of expertise in this technology in Uganda is vital, and this project will contribute by providing training to a cohort of Ugandan scientists in laboratory techniques, bioinformatics, and molecular epidemiology. 

Malaria molecular surveillance in this project will include surveillance for drug and diagnostic resistance. Antimalarial drug resistance, particularly to artemisinins, is of particular concern in Uganda where artemisinin-combination therapy (ACT) is the standard of care for uncomplicated malaria. Recent studies by our group and others have identified the emergence of artemisinin resistance in Uganda. By collecting genomic information twice yearly at locations across the country, our study will allow for increased monitoring of drug resistance mutations and provide a way to monitor their spread. In addition, we will monitor for HRP2/3 deletions, which allow malaria infections to escape detection by most rapid diagnostic tests. 

In addition, genomic data has the potential to enhance our ability to measure transmission intensity by measuring the heterogeneity of the malaria infections circulating among the human population. The project plans to combine molecular metrics derived from highly variable regions of the parasite genome with epidemiologic data collected at health facilities to better understand how molecular metrics can be used to enhance routine surveillance. This approach may improve geographic stratification of malaria transmission intensity, more efficiently monitor the impact of interventions over time, and provide detailed information regarding drivers of transmission in areas of low transmission to inform efforts at enhanced control and elimination. 

Our long association with the IDRC (Infectious Diseases Research Collaboration) and Makerere University has helped to develop the current malaria surveillance network and productive relationships with scientists and epidemiologists in Uganda. In this project, by involving the Ministry of Health at every step, we hope to ensure technical expertise is translated from the lab to the policy brief. In addition, we hope that this work provides opportunities for collaboration with Africa CDC and the NIH-funded African Center of Excellence in Bioinformatics (ACE) so that malaria genomics expertise continues to expand in Uganda. 

This new award aligns and builds off of Dr. Briggs’ previous Bill & Melinda Gates Foundation award, UnMASC: Uganda Malaria Actionable Surveillance in the time of Coronavirus. The Gates foundation has provided us the opportunity to create a sustained impact, building the pool of experts and sustaining the relationships that will create change.