Chapel Hill, NC — Researchers with the UNC Institute for Global Health and Infectious Diseases (IGHID), in collaboration with the UNC Lineberger Comprehensive Cancer Center, and UNC Project-Malawi, found adults receiving rituximab as part of cancer treatment face a significantly higher risk of developing symptomatic malaria in an endemic region. Led by Matthew Painschab, MD, the study was published in eClinicalMedicine (The Lancet Discovery Science), highlighting an emerging safety concern as rituximab use expands across sub‑Saharan Africa.
Rituximab is an anti‑CD20 monoclonal antibody on the World Health Organization’s Essential Medicines List that has transformed care for B‑cell lymphomas and autoimmune diseases. While the immunosuppressive effects of rituximab are well documented, the impact of rituximab on malaria risk has never been studied in endemic regions—until now.
“Rituximab is used for many B-cell malignancies and autoimmune diseases, including rheumatoid arthritis, lupus, and autoimmune cytopenias, and its use is increasing globally,” said Painschab, assistant professor of hematology.
“However, our findings suggest rituximab may increase vulnerability to clinically significant malaria in adults living in endemic regions. As rituximab becomes more widely available in Africa, understanding this risk is essential for patient safety.”
Study Design and Findings
Researchers conducted a post-hoc analysis of 96 adults with diffuse large B‑cell lymphoma, the most common aggressive type of non-Hodgkin lymphoma, treated at Kamuzu Central Hospital in Lilongwe, Malawi, between 2013 and 2019. The analysis looked at participants who received CHOP chemotherapy, a cornerstone combination treatment of four drugs which work together to kill fast-growing cancer cells from different angles, and R‑CHOP (with Rituximab added).
Stored plasma samples were analyzed for HRP2 antigenemia (Histidine-Rich Protein 2 from Plasmodium falciparum malaria parasites) and malaria‑specific antibody responses over multiple time points. Among the 14 participants who developed symptomatic malaria, 24% were in the R‑CHOP group, compared with 8% in the CHOP group.
Participants receiving rituximab plus chemotherapy were 3.5 times more likely to develop symptomatic malaria than those receiving chemotherapy alone. HRP2 antigenemia, a marker of recent malaria infection, occurred at similar rates in both groups; however, patients on rituximab had significantly higher HRP2 concentrations, suggesting a greater parasite burden.
Jon Juliano, MD, MSPH, professor of medicine and co-founder of the IDEEL Lab (Infectious Disease Epidemiology and Ecology), recognizes that malaria’s impact on global health is intensifying in vulnerable settings.
“Malaria remains a major threat for public health, and it has been worsening in many areas of Africa over the last five years,” Juliano said. “Any understanding of populations that are at increased risk for infection will help us better treat patients and control transmission.”
The Kamuzu Central Hospital Lymphoma Study is the largest prospective of diffuse large B-Cell Lymphoma in sub-Saharan Africa and the first to demonstrate the safety and efficacy of rituximab in this setting. But the underlying pathogenesis of severe malaria is complex and influenced by both cellular and humoral immunity,the immune response mediated by B cells, involving the production of antibodies to fight against pathogens.
“Lymphoma patients often exhibit a suppressed cellular immune response and, therefore, it is possible that a patient may contract malaria infection with high parasite burden but develop less severe disease due to lower levels of inflammatory cytokines associated with severe disease,” explained Painschab. “These patients could be more susceptible to malaria infection without displaying severe malaria symptoms and complications; however, much more work is needed to understand the complex immunology of malaria in the setting of lymphoma and B-cell depletion.”
Implications for Care
The study underscores the need for prospective research to determine whether malaria prophylaxis should be recommended for patients receiving rituximab in endemic regions. As rituximab becomes more affordable and cancer care infrastructure expands, the number of patients exposed to this risk will continue to grow.
Future prospective studies explicitly designed to assess the risk of malaria and to determine the value and timing of antimalarial prophylaxis should be performed as rituximab and other B-cell depleting medication use becomes more widespread in areas where malaria remains endemic.
The study team also included Yuri Fedoriw, MD, IGHID Director of Global Cancer Pathology, Satish Gopal, MD, MPH (National Cancer Institute), and first author Luke Eastburg, MD, (Corewell Health Grand Rapids, Michigan/Former IGHID fellow).
UNC Institute for Global Health and Infectious Diseases
Established in 2007, the UNC Institute for Global Health & Infectious Diseases at the UNC School of Medicine started over 30 years ago with infectious disease physician researchers studying HIV in China and Malawi. Through the years, our work has expanded to include emerging pathogens, cancer, women’s health and vector-borne disease like malaria–shaping policy through evidence-based research around the world. At UNC-Chapel Hill, the Institute facilitates research excellence while nurturing emerging scientists to advance patient care and practice, addressing the most important global health issues of our time–through research, training and service.