Person:
Meibalan, Elamaran

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Meibalan

First Name

Elamaran

Name

Meibalan, Elamaran
Author's Publications: search.filters.isAuthorOfPublication.bd5cf3d6-d94f-44f7-9efc-762f08e20ea5

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda
    (Nature Publishing Group, 2016) Chang, Hsiao-Han; Meibalan, Elamaran; Zelin, Justin; Daniels, Rachel; Eziefula, Alice C.; Meyer, Evan C.; Tadesse, Fitsum; Grignard, Lynn; Joice, Regina C.; Drakeley, Chris; Wirth, Dyann; Volkman, Sarah K.; Buckee, Caroline; Bousema, Teun; Marti, Matthias
    Artemisinin resistance is rapidly spreading in Southeast Asia. The efficacy of artemisinin-combination therapy (ACT) continues to be excellent across Africa. We performed parasite transcriptional profiling and genotyping on samples from an antimalarial treatment trial in Uganda. We used qRT-PCR and genotyping to characterize residual circulating parasite populations after treatment with either ACT or ACT-primaquine. Transcripts suggestive of circulating ring stage parasites were present after treatment at a prevalence of >25% until at least 14 days post initiation of treatment. Greater than 98% of all ring stage parasites were cleared within the first 3 days, but subsequently persisted at low concentrations until day 14 after treatment. Genotyping demonstrated a significant decrease in multiplicity of infection within the first 2 days in both ACT and ACT-primaquine arms. However, multiple clone infections persisted until day 14 post treatment. Our data suggest the presence of genetically diverse persisting parasite populations after ACT treatment. Although we did not demonstrate clinical treatment failures after ACT and the viability and transmissibility of persisting ring stage parasites remain to be shown, these findings are of relevance for the interpretation of parasite clearance transmission dynamics and for monitoring drug effects in Plasmodium falciparum parasites.
  • Thumbnail Image
    Publication
    Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow
    (American Association for the Advancement of Science, 2018) De Niz, Mariana; Meibalan, Elamaran; Mejia, Pedro; Ma, Siyuan; Brancucci, Nicolas M. B.; Agop-Nersesian, Carolina; Mandt, Rebecca; Ngotho, Priscilla; Hughes, Katie R.; Waters, Andrew P.; Huttenhower, Curtis; Mitchell, James; Martinelli, Roberta; Frischknecht, Friedrich; Seydel, Karl B.; Taylor, Terrie; Milner, Danny; Heussler, Volker T.; Marti, Matthias
    Transmission of Plasmodium parasites to the mosquito requires the formation and development of gametocytes. Studies in infected humans have shown that only the most mature forms of Plasmodium falciparum gametocytes are present in circulation, whereas immature forms accumulate in the hematopoietic environment of the bone marrow. We used the rodent model Plasmodium berghei to study gametocyte behavior through time under physiological conditions. Intravital microscopy demonstrated preferential homing of early gametocyte forms across the intact vascular barrier of the bone marrow and the spleen early during infection and subsequent development in the extravascular environment. During the acute phase of infection, we observed vascular leakage resulting in further parasite accumulation in this environment. Mature gametocytes showed high deformability and were found entering and exiting the intact vascular barrier. We suggest that extravascular gametocyte localization and mobility are essential for gametocytogenesis and transmission of Plasmodium to the mosquito.
  • Thumbnail Image
    Publication
    Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection
    (American Society for Microbiology, 2018) Obaldia, Nicanor; Meibalan, Elamaran; Sa, Juliana M.; Ma, Siyuan; Clark, Martha; Mejia, Pedro; Moraes Barros, Roberto R.; Otero, William; Ferreira, Marcelo U.; Mitchell, James; Milner, Danny; Huttenhower, Curtis; Wirth, Dyann; Duraisingh, Manoj; Wellems, Thomas E.; Marti, Matthias
    ABSTRACT Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of P. vivax stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of P. vivax and Plasmodium falciparum blood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP (Aotus sp.). Histological analyses of P. vivax parasites in organs of 13 infected NHP (Aotus and Saimiri species) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites.