The extravascular compartment of the bone marrow: a niche for Plasmodium falciparum gametocyte maturation?

Abstract

Background: Plasmodium falciparum immature gametocytes accumulate in the bone marrow, but their exact location in this tissue remains unclear.

Methods: The stage and deposition pattern of gametocytes was analysed on histological sections of a bone marrow sample collected in a patient with subacute P. falciparum malaria.

Results: A majority (89%) of immature stages II to IV gametocytes and a minority (29%) of mature stage V gametocytes were observed in extravascular spaces.

Discussion and conclusion: These observations represent a valuable step towards understanding sequestration patterns of P. falciparum gametocytes and may ultimately lead to novel transmission-blocking interventions.

Figure 1

Gametocyte staging on Giemsa-stained smears (cytology, reference method) and on HES-stained sections (histology) from the same bone marrow biopsy sample described in this report. Leaf-shaped forms, hemi-ellipsoid forms, forms with at least one sharp extremity, and crescent forms with two rounded extremities, a concave and a convex border were counted as stage II, III, IV and V, respectively (columns II-V). A form with finely distributed pigment, but not falling into any of the previous categories, was categorized as undetermined stage (column U). Counting results appear on Table 1.

Figure 2

A (arrow and Ai insert) and B: HES-stained bone marrow sections showing immature gametocytes - elongated shape, pink and purple staining, finely distributed pigment – outside small vessels (vl) and in close contact with resident cells such as adipocytes (ad) or erythroblasts (e). The dotted line in A highlights the vessel wall. C: Mature stage V gametocyte close to a mature red blood cell (C, r) in the lumen of a vessel. D and E: Immunohistochemistry (antibodies revealed with peroxydase) showing gametocytes (arrows) distant from CD34-positive vascular structures (vl) or CD68-positive macrophages (mf).