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1.
Clin Infect Dis ; 73(Suppl_5): S382-S389, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910181

RESUMO

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. RESULTS: Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02-0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. CONCLUSIONS: Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors.


Assuntos
Desnutrição , Autopsia/métodos , Biópsia , Criança , Humanos , Lactente , Pobreza , Manejo de Espécimes
2.
Sci Transl Med ; 16(764): eadk9149, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259811

RESUMO

COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19. We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: "early death" (<15 days until death) and "late death" (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2+ macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2+ epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (TH17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, TH2 responses, and anti-inflammatory-mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes.


Assuntos
COVID-19 , Progressão da Doença , Pulmão , SARS-CoV-2 , Humanos , COVID-19/sangue , COVID-19/diagnóstico , Pulmão/patologia , SARS-CoV-2/isolamento & purificação , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Análise de Célula Única , Adulto , Brasil , Idoso
3.
Emerg Infect Dis ; 19(6): 981-4, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23735189

RESUMO

A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing.


Assuntos
Melioidose/diagnóstico , Antibacterianos/uso terapêutico , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/isolamento & purificação , Humanos , Lactente , Malaui , Masculino , Melioidose/tratamento farmacológico , Melioidose/microbiologia , Resultado do Tratamento
4.
Cell Microbiol ; 13(2): 198-209, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21029292

RESUMO

Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (EC(CM) ) or UM (EC(UM) ) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, EC(CM) displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with EC(UM) . The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in EC(CM) than in EC(UM) . These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria.


Assuntos
Células Endoteliais/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Fator de Necrose Tumoral alfa/imunologia , Encéfalo/imunologia , Micropartículas Derivadas de Células/metabolismo , Células Cultivadas , Quimiocina CCL2/biossíntese , Quimiocina CCL5/biossíntese , Humanos , Integrina beta3/biossíntese , Molécula 1 de Adesão Intercelular/biossíntese , Interleucina-6/biossíntese , Malária Falciparum/patologia , Plasmodium falciparum/patogenicidade , Molécula 1 de Adesão de Célula Vascular/biossíntese
5.
Methods Mol Biol ; 2470: 765-777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35881388

RESUMO

In this chapter we present the methods for using biopsies of skin or subcutaneous tissue to examine the interactions between parasitized red blood cells and endothelial cells in patients with malaria infection. Punch biopsy can be used to obtain all skin layers and needle biopsy to obtain subcutaneous tissue. Smears are useful for spreading vessels on a slide for immunofluorescence staining. Specimens can be fixed and embedded for sectioning and traditional histological or immunostaining techniques or confocal microscopy with three-dimensional reconstruction. Finally, endothelium can be dissociated, allowing individual cells to be isolated for culture and ex vivo assays or used for immunophenotyping.


Assuntos
Células Endoteliais , Malária , Adesão Celular , Eritrócitos , Humanos , Plasmodium falciparum , Pele , Tela Subcutânea
6.
J Infect ; 72 Suppl: S41-9, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27180312

RESUMO

Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/enzimologia , Resistência beta-Lactâmica , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , Proteínas de Bactérias/biossíntese , Criança , Colistina/administração & dosagem , Colistina/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Fosfomicina/administração & dosagem , Fosfomicina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , beta-Lactamases/biossíntese
7.
Mol Biochem Parasitol ; 166(2): 99-108, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19450727

RESUMO

Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection and represents a major cause of morbidity and mortality worldwide. The nature of the pathogenetic processes leading to the cerebral complications remains poorly understood. It has recently emerged that in addition to their conventional role in the regulation of haemostasis, coagulation factors have an inflammatory role that is pivotal in the pathogenesis of a number of acute and chronic conditions, including CM. This new insight offers important therapeutic potential. This review explores the clinical, histological and molecular evidence for the dysregulation of the coagulation system in CM, looking at possible underlying mechanisms. We discuss areas for future research to improve understanding of CM pathogenesis and for the development of new therapeutic approaches.


Assuntos
Fatores de Coagulação Sanguínea/imunologia , Coagulação Sanguínea , Malária Cerebral/sangue , Plasmodium falciparum/imunologia , Animais , Encéfalo/imunologia , Encéfalo/parasitologia , Encéfalo/patologia , Humanos , Malária Cerebral/imunologia , Malária Cerebral/parasitologia , Malária Cerebral/patologia
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