title: Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in bone marrow.
abstract: Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as bone marrow have never been assessed by molecular techniques, which are more sensitive than optical microscopy. We quantified P falciparum sexual stages in bone marrow (n = 174) and peripheral blood (n = 70) of Mozambican anemic children by quantitative polymerase chain reaction targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n = 136) and peripheral blood (n = 25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P < .001), as were transcript levels (P < .001 for both stages). In contrast, mature gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence interval 1.49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24-17.25) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as the relationship between hematological disturbances and gametocyte development in this tissue.
authors: Barcelona Centre for International Health Research (CRESIB), Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain;
authors: Ruth
authors: R
authors: Aguilar
authors: Ariel
authors: A
authors: Magallon-Tejada
authors: Ariel H
authors: AH
authors: Achtman
authors: Cinta
authors: C
authors: Moraleda
authors: Regina
authors: R
authors: Joice
authors: Pau
authors: P
authors: Cisteró
authors: Connie S N
authors: CS
authors: Li Wai Suen
authors: Augusto
authors: A
authors: Nhabomba
authors: Eusebio
authors: E
authors: Macete
authors: Ivo
authors: I
authors: Mueller
authors: Matthias
authors: M
authors: Marti
authors: Pedro L
authors: PL
authors: Alonso
authors: Clara
authors: C
authors: Menéndez
authors: Louis
authors: L
authors: Schofield
authors: Alfredo
authors: A
authors: Mayor
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000235:genetics / Q000469:parasitology; D000818:Animals; D001853:Bone Marrow / Q000469:parasitology* / Q000473:pathology; D002648:Child; D016054:DNA, Protozoan / Q000032:analysis; D005260:Female; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000235:genetics / Q000469:parasitology; D008297:Male; D025202:Molecular Diagnostic Techniques; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D016054:DNA, Protozoan