Pathology of the Ruptured Spleen in Acute Vivax Malaria

Lubitz, Joseph M.

doi:10.1182/blood.v4.10.1168.1168

Cited by 28 publications

(12 citation statements)

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“…Indirect evidence points to accumulation of non-phagocytosed P . vivax iRBCs in the spleen in acute malaria [ 4 , 10 ], with supporting direct evidence from case reports [ 6 , 32 ]. Furthermore, early splenic rupture may occur more frequently in P .…”

Section: Discussionmentioning

confidence: 58%

“…The extent to which this occurs in early infection and in clinical disease is not clear. Indirect evidence points to accumulation of non-phagocytosed P. vivax iRBCs in the spleen in acute malaria [4,10], with supporting direct evidence from case reports [6,32]. Furthermore, early splenic rupture may occur more frequently in P. vivax compared to P. falciparum infection [33], which may suggest a greater tropism of this species for the spleen.…”

Section: Plos Medicinementioning

confidence: 80%

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Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study

et al. 2021

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Background Plasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum, which is known to undergo microvascular tissue sequestration, little is known about the behavior of P. vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life. Methods and findings To identify organ-specific changes during the early stages of P. vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P. vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P. falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species (n = 3 P. vivax; n = 4 P. falciparum). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume (P. vivax: +28.8% [confidence interval (CI) +10.3% to +57.3%], P. falciparum: +22.9 [CI −15.3% to +61.1%]) and radiotracer uptake (P. vivax: +15.5% [CI −0.7% to +31.7%], P. falciparum: +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P. vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow (P. vivax: +4.6% [CI −15.9% to +25.0%], P. falciparum: +3.2% [CI −3.2% to +9.6%]) or liver (P. vivax: +6.2% [CI −8.7% to +21.1%], P. falciparum: −1.4% [CI −4.6% to +1.8%]) following infection with either species. In participants with P. vivax, hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P. vivax infection compared to P. falciparum. The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity. Conclusions PET/MRI indicated greater splenic tropism and metabolic activity in early P. vivax infection compared to P. falciparum, supporting the hypothesis of splenic accumulation of P. vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.

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Section: Discussionmentioning

confidence: 58%

Section: Plos Medicinementioning

confidence: 80%

Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study

et al. 2021

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“…Splenic rupture is a life‐threatening but probably under‐reported complication in adults (Moses ; Kapland et al . ; Kitchen 1949a; Lubitz ; Imbert et al . ; Lacerda et al .…”

Section: Section 13: Severe Vivax Malariamentioning

confidence: 99%

Severe Malaria

2014

Tropical Med Int Health

465

354

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Fever and diarrhea developed in a 34-year-old Swiss man two weeks after his return from Madagascar. Before his visit he had not taken any prophylactic antimalarial drugs. Despite self-treatment with ciprofloxacin and metronidazole, he remained febrile. He also reported hematuria and dark urine. On admission, his temperature was 39.2°C and his vital signs and mental status were normal. The abdomen was tender, and the spleen was palpable 15 cm below the costal margin. The hemoglobin level was 12.4 g per deciliter, the hematocrit was 35 percent, the white-cell count was 8500 per cubic millimeter, and the platelet count was 15,000 per cubic millimeter. The creatinine level was 2.6 mg per deciliter (234 µmol per liter), the lactate dehydrogenase level was 1920 U per liter (normal, 187 to 443), and the bilirubin level was 11.5 mg per deciliter (197 µmol per liter); the results of other liver-function tests were in the normal range. Examination of blood smears showed severe infestation with Plasmodium falciparum, with 70 to 80 percent of red cells containing up to five parasites (small ring forms) per cell (long arrow in Panel A). Other features of P. falciparum that were present included chromatin dots (arrowheads in Panel A) and appliqué forms (short arrow in Panels A and B; Wright's stain, ¬1000). About 70 percent of the neutrophils contained hemozoin (shown in a band form [long arrows] in Panel B). The patient was treated with intravenous quinine sulfate and exchange transfusions, with dramatic improvement. The degree of parasitemia fell to 65 percent after the first exchange transfusion and to 8 percent after the second. The patient's course was complicated by acute renal failure, the acute respiratory distress syndrome, and spontaneous rupture of the spleen, necessitating continuous hemofiltration, mechanical ventilation, and laparotomy with splenectomy. Despite these complications , the patient was able to return home within three months and was well at the last follow-up visit.

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“…Splenectomy has also revealed the importance of the spleen in infections with Plasmodium vivax. In fact, pathological examinations of post-surgery spleens due to P. vivax infections revealed extensive remodelling, intense phagocytosis and local infarction (Lubitz, 1949). In addition, the P. vivax genome, like that of P. falciparum, contains subtelomeric multigene families putatively involved in antigenic variation (del Portillo et al, 2001;Carlton et al, 2008).…”

Section: Humansmentioning

confidence: 99%

The role of the spleen in malaria

Portillo

Ferrer

Brugat³

et al. 2012

Cellular Microbiology

182

158

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Summary The spleen is a complex organ that is perfectly adapted to selectively filtering and destroying senescent red blood cells (RBCs), infectious microorganisms and Plasmodium‐parasitized RBCs. Infection by malaria is the most common cause of spleen rupture and splenomegaly, albeit variably, a landmark of malaria infection. Here, the role of the spleen in malaria is reviewed with special emphasis in lessons learned from human infections and mouse models.

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Pathology of the Ruptured Spleen in Acute Vivax Malaria

Cited by 28 publications

References 5 publications

Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study

Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study

Severe Malaria

The role of the spleen in malaria

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