Hematologic Malignancies in Malawi

By Sneha Makhijani

Illustration by Hannah Kennedy

Few people would have thought that it is possible to develop cancer by simply sharing their spoon of ice cream with a friend. However, the common human herpesvirus Kaposi’s sarcomaassociated herpes virus (KSHV) is transmitted through saliva (for instance on a spoon), sexual contact, or transfusion of contaminated blood or tissue. The virus hides in the body and does not usually cause problems unless the immune system is weakened in cases such as in those with human immunodeficiency virus (HIV). KSHV can cause multicentric Castleman disease (MCD) in some patients with HIV. MCD is a rare disease that presents with similar symptoms to lymphoma. The HIV/AIDS (acquired immune deficiency syndrome) epidemic greatly affected the African country of Malawi. The prevalence of HIV among adults is around 9% and before the link between HIV and cancer was well understood, many people living with HIV mysteriously suffered from lymphoma and other cancers. In 1990, the UNC Chapel Hill Institute for Global Health and Infectious Diseases, in collaboration with the Malawi Ministry of Health (MOH), formed UNC Project Malawi in order to focus Matthew Painschab, MD research and training around HIV and other sexually transmitted diseases (STDs). Since 1990, UNC Project Malawi has spearheaded treatment and research on HIV and STDs in Malawi with physicians like Dr. Matthew Painschab at the forefront. Dr. Painschab’s main research focus has been on HIV and its association with hematologic malignancies, specifically the two blood cancers leukemia and lymphoma. Dr. Painschab has always had a passion for public health and medicine as a first-generation college student with interests in biol-

Figure 1. A representative lymph node biopsy from a patient with multicentric Castleman disease in Malawi demonstrating a) the classic convulted germinal center surrounded by b) Kaposi sarcoma herpesvirus (KSHV)infected plasmablasts that stain brown for a protein made by KSHV.

ogy and international development. After completing a research fellowship in Puno, Peru during medical school, he pursued a career in oncology with a focus on global health. In his career, Dr. Painschab hopes to deliver cancer treatment and research that will have a tremendous impact on communities. He states, “[Standardized] treatment protocols go a long way in saving lives…so that the children and young ones don’t become orphans.” 1 During his Hematology/Oncology fellowship, he began to work with UNC Project Malawi, where he has further developed his interest and passion for his medical and research work. Dr. Painschab first became involved in research with UNC Project Malawi through his fellowship research mentor, Dr. Satish Gopal. Throughout his clinical career, Dr. Painschab’s primary area of research has focused on HIV-associated cancers and implementation of cancer care in low-resource settings. His main motivation for continuing his work with UNC Project Malawi has been to help treat citizens of Malawi suffering from HIV-associated cancers while also promoting awareness for, and educating the citizens of Malawi about the diseases and their prevention. Optimizing treatment and spreading awareness are two critical aspects of patient care in Malawi.

While working in Malawi, Dr. Painschab was exposed to MCD, one of the most common lymphoproliferative diseases treated and observed in the studies from UNC Project Malawi at the National Cancer Treatment Centre at Kamuzu Central Hospital in the capital city of Lilonge, Malawi. There are two types of MCD: idiopathic MCD, which has no known cause and is more frequently found in the U.S., and KSHV-associated MCD, which is more common in Sub-Saharan African populations due to the high prevalence of both KSHV and HIV in this region. For example, the U.S. National Cancer Institute has had approximately 60 cases of MCD over a 15-year period, referred from all over the United States. On the other hand, since starting to collect patient samples and recognize the disease seven years ago, Malawi has already seen over 35 cases. With new advancements in healthcare, Dr. Painschab and his fellow research team are able to improve MCD detection and are improving the diagnosis of MCD as it is thought to be underdiagnosed in the region. Further, Dr. Painschab and his team are also working on improving patient recovery after MCD. When the project first started, Dr. Painschab and his team found that patients in Malawi affected by MCD experienced symptoms characteristic of lymphoma, such as fevers, loss of appetite, weight loss, and night sweats. It was difficult to recognize MCD because it could have easily been mistaken for a plethora of diseases like tuberculosis and several forms of cancer. Tissue biopsies are a major diagnostic tool for confirming the presence of MCD in patients, and using new tissue biopsy facilities constructed by UNC Project Malawi, the team has been able to better diagnose and treat MCD. Since MCD is rare in high-income countries, it has not been extremely well-studied. KSHV is a common virus endemic to Sub-Saharan Africa. Up to 80% of the population is reportedly infected with KSHV, which can cause MCD, Kaposi sarcoma, or lymphoma in those with immunodeficiencies. MCD causes marked inflammation in the body which leads to severe anemia, extreme bleeding events (due to low platelets), and dangerously low blood pressure, ultimately resulting in high mortality rates without treatment. MCD can be controlled with chemotherapy, but relapses are common and new therapies, such as a medication called rituximab, are urgently needed and are being studied by the team at UNC Project Malawi.

Rituximab, an alternative to chemotherapy, is an antibody medication used to treat certain autoimmune diseases and some types of cancer. Rituximab has already worked well in high-income countries like in the U.S., but it has also shown promising results in low-income countries like Malawi, showing positive results in greater than 90% of treated cases. This medicine has side effects; for example, Malawian patients that had been treated with rituximab showed a much higher risk of malaria than nonrituximab patients. Dr. Painschab’s team is currently working on measuring the efficacy and side effects of rituximab for MCD in Malawi as this can have huge implications for many other diseases as well. Through the intersection of research and patient-care, Dr. Painschab makes a difference not in the lives of his patients both in the United States and in Malawi. He hopes that by studying HIV, lymphomas, and MCD, the team at UNC Project Malawi will make a difference in the field of medicine and help people throughout the world lead longer and healthier lives.

Figure 2. One of the UNC Project Malawi nurses preparing chemotherapy.

Figure 3. Kaplain-Meier survival curves showing time to disease relapse or death in patients with multicentric Castleman disease after treatment with a) chemotherapy and b) rituximab, demonstrating the clear superiority of rituximab.

References

1. Interview with Matthew Painschab, MD. 02/24/2021 2. Shin, D.-Y.; Jeon, Y.K.; Hong, Y.-S.; Kim, T.M.; Lee, S.-H.;

Kim, D.-W.; Kim, I.; Yoon, S.-S.; Heo, D.S.; Park, S.; et al.

Leuk. Lymphoma 2011, 52, 1517-22. 3. Gopal, S.; Fedoriw, Y.; Montgomery, N.D.; Kampani, C.;

Krysiak, R.; Sanders, M.K.; Dittmer, D.P.; Liomba, N.G.

Lancet 2014, 384, 1158. 13