June 1, 2021

Hidden malaria life cycle discovered in the spleen

Ground-breaking studies published last week in the New England Journal of Medicine and PLOS Medicine have found large numbers of malaria parasites hiding in the human spleen where they actively multiply in a previously unrecognised life cycle.

Until now, it was thought that once malaria parasites reached the blood stream, they circulated and multiplied only in the blood. New research, led by Indonesian PhD student Steven Kho at Australia’s Menzies School of Health Research (Menzies), Dr. Rintis Noviyanti, Dr Nurjati Siregar and Dr Leily Trianty at Jakarta’s Eijkman Institute for Molecular Biology and Dr Putu Ayu Indrashanti Wardani at Rumah Sakit Umum Daerah (RSUD) in Timika, Dr Enny Kenangalem and Dr Jeanne Rini Poesprodjo and their Research Team at the Yayasan Pengembangan Kesehatan dan Masyarakat Papua (YPKMP) with partners in Australia and France, found that in chronic malaria, concentrations of parasites were hundreds to thousands of times higher in the spleen than found in the circulating blood.

Dr Kho examined spleens from people in Papua, Indonesia who needed spleen removal following road accidents. He found that the patients generally had no symptoms of malaria before the accident, but 95 percent of patients had large numbers of live parasites hiding in the spleen.

“Our findings redefine the malaria life-cycle. Chronic malaria should be considered predominantly an infection of the spleen, with just a small proportion circulating in the blood,” Dr Kho said.

“Accumulation of parasites in the spleen was found with both major Plasmodium species causing malaria, but was particularly apparent in Plasmodium vivax, where over 98 percent of all the parasites in the body were hiding in the spleen”.

Figure. Patient's spleen tissue as examined by Transmission Electron Microscope (TEM) showing malaria parasites.

Dr Siregar says the research also found that the human spleen traps large numbers of very young red blood cells, called reticulocytes, which are the only type of red cell that Plasmodium vivax can infect.

“This makes the spleen a location in which the vivax malaria parasites can easily multiply” said Dr Siregar.

Co-author Dr Wardani says that until now the spleen has been mainly considered to be an organ that destroys malaria parasites and which parasites try to avoid.

“While the spleen does filter out and destroy some parasites, we now show it also provides a shelter for long-term persistence of parasites” explained Dr Wardani.

The research team emphasise the importance of the findings. Co-author Dr Trianty says that persistent infection of the spleen has major clinical and public health implications, including a significant contribution to anaemia.

” We also found that some people with large numbers of parasites hiding in the spleen do not have parasites detectable in the blood” said Dr Trianty.

“This suggests that malaria elimination programs relying on mass testing of blood and only treating those with detectable infection may not be capturing all infections in populations where malaria occurs. The study is continuing in Timika, Papua, to further explore this newly-discovered parasite population in the spleen” explained Co-author Dr Noviyanti.

“Malaria elimination requires joint efforts between various institutions with various expertise. Research into the parasite biology will generate knowledge needed to understand the basic mechanisms of this pathogen in evading the host immunity. These insights will facilitate the finding of the best approach and intervention to defeat malaria,” Dr Noviyanti said.

The papers are available here:

  1. Kho, et al. NEJM 2021 paper
  2. Kho, et al. PLoS Medicine 2021 paper