To study the pathogenesis of fatal cerebral malaria, we conducted autopsies in 31 children with this clinical diagnosis. We found that 23% of the children had actually died from other causes. The remaining patients had parasites sequestered in cerebral capillaries, and 75% of those had additional intra- and perivascular pathology. Retinopathy was the only clinical sign distinguishing malarial from nonmalarial coma. These data have implications for treating malaria patients, designing clinical trials and assessing malaria-specific disease associations.
The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
Pediatric cerebral malaria carries a high mortality rate in sub-Saharan Africa. We present our systematic analysis of the descriptive and quantitative histopathology of all organs sampled from a series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and control patients (without coma, or without malaria infection) who were clinically well characterized prior to death. We found brain swelling in all cerebral malaria patients and the majority of controls. The histopathology in patients with sequestration of parasites in the brain demonstrated two patterns: (a) the “classic” appearance (i.e., ring hemorrhages, dense sequestration, and extra-erythrocytic pigment) which was associated with evidence of systemic activation of coagulation and (b) the “sequestration only” appearance associated with shorter duration of illness and higher total burden of parasites in all organs including the spleen. Sequestration of parasites was most intense in the gastrointestinal tract in all parasitemic patients (those with cerebral malarial and those without).
AimsWe performed an audit to evaluate the impact of the COVID-19 pandemic-related delay in the diagnosis of major cancers at a Pathology Unit of a Secondary Care Hospital Network in Italy.MethodsA comparison was made among the number of first cellular pathological diagnoses of malignancy made from the 11th to the 20th week of the years 2018–2020.ResultsCancer diagnoses fell in 2020 by 39% compared with the average number recorded in 2018 and 2019. Prostate cancer (75%) bladder cancer (66%) and colorectal cancer (CRC; 62%) had the greatest decrease. CRC was identified as carrying a potentially important diagnostic delay.ConclusionsFor CRC corrective procedures (continuing mass screening tests; patient triage by family physicians; diagnostic procedures alternative to colonoscopy; predictive evaluation on biopsy samples) were advised. Our simple audit model is widely applicable to avoid pandemic-related delay in clinical diagnosis of cancer.
Background: Multiple studies have compared the performance of artificial intelligence (AI)ebased models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice.
Retinal haemorrhages increase in number with severity of Plasmodium falciparum malaria and occur in 35-40% of children with cerebral malaria. We performed clinical retinal examinations and histopathological examinations of retina, and parietal and cerebellar sections of the brains, in 33 children in Malawi who died with cerebral malaria, severe malaria anaemia, or coma of other causes. Haemorrhages were counted in a standardized fashion: the Spearman correlation coefficient between the number of haemorrhages in retina and brain was 0.741 for parietal tissue and 0.703 for cerebellar (P < 0.01 for both). Severity of haemorrhage in the retina correlates well with that in the brain. Retinal examination in cerebral malaria is a useful tool in predicting some of the pathophysiological processes occurring in the brain.
Children in sub-Saharan Africa continue to acquire and die from cerebral malaria, despite efforts to control or eliminate the causative agent, Plasmodium falciparum. We present a quantitative histopathological assessment of the sequestration of parasitized erythrocytes in multiple organs obtained during a prospective series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi, on pediatric patients who died from cerebral malaria and controls. After the brain, sequestration of parasites was most intense in the gastrointestinal tract, both in patients with cerebral malaria and those with parasitemia in other organs. Within cases of histologically defined cerebral malaria, which includes phenotypes termed "sequestration only" (CM1) and "sequestration with extravascular pathology" (CM2), CM1 was associated with large parasite numbers in the spleen and CM2 with intense parasite sequestration in the skin. A striking histological finding overall was the marked sequestration of parasitized erythrocytes across most organs in patients with fatal cerebral malaria, supporting the hypothesis that the disease is, in part, a result of a high level of total-body parasite sequestration.
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