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Master's Dissertation
DOI
https://doi.org/10.11606/D.5.2023.tde-21112023-132925
Document
Author
Full name
Fernanda Gurgel de Oliveira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Bermúdez, José Ernesto Vidal (President)
Gryschek, Ronaldo Cesar Borges
Kalichman, Artur Olhovetchi
Oliveira, Augusto César Penalva de
Title in Portuguese
Prevalência de antigenemia criptocócica, utilizando o teste de fluxo lateral em sangue periférico de PVHA com doença avançada e sintomas neurológicos: estudo de coorte prospectiva em pronto socorro de hospital terciário em São Paulo, Brasil
Keywords in Portuguese
Criptococose
Diagnóstico
Meningite criptocócica
Serviços médicos de emergência
Síndrome de imunodeficiência adquirida
Sistema nervoso central
Abstract in Portuguese
Introdução: O diagnóstico oportuno é fundamental no manejo da criptococose do sistema nervoso central (SNC) em pessoas que vivem com HIV/AIDS (PVHA). O objetivo desse estudo foi avaliar a prevalência da antigenemia criptocócica e da criptococose do SNC em PVHA e imunossupressão avançada que apresentaram sintomas neurológicos, utilizando o teste de fluxo lateral (LFA) em sangue periférico, realizado à beira-leito, sem a utilização de estrutura laboratorial, no pronto socorro (PS) de um serviço de referência em doenças infectocontagiosas em São Paulo, Brasil, além de descrever as principais características dessa população e propor um algoritmo de manejo inicial para esse perfil de pacientes. Métodos: Estudo de coorte prospetivo realizado no PS do Instituto de Infectologia Emilio Ribas (IIER), entre janeiro e setembro de 2020. Todos os pacientes incluídos foram submetidos ao LFA em sangue periférico, e aqueles com resultado positivo, foram submetidos à punção lombar para coleta de líquido cefalorraquidiano (LCR) e realização do LFA nesse material. O manejo diagnóstico e terapêutico dos casos incluídos seguiu as rotinas institucionais. Resultados: Durante o período do estudo, 497 PVHA foram admitidas no PS do IIER, dos quais 74 (14,9%) foram incluídos. A idade mediana (IIQ) foi de 40 (30-48) anos com predomínio do sexo masculino (62%). As medianas (IIQ) da contagem de linfócitos T CD4 e da carga viral do HIV foram 43 (20-130) células/ml e 36.401 (457-288055) cópias/ml, respectivamente. Todos os casos incluídos tinham diagnóstico prévio de infecção pelo HIV. O tempo entre o início dos sintomas e a admissão hospitalar teve uma mediana (IIQ) de 15 (6-39) dias. As principais manifestações neurológicas foram cefaleia (41/74, 55,4%), alteração da consciência (35/74, 47,3%) e déficit motor focal (31/74, 41,9%). A criptococose foi a causa mais frequente de meningoencefalite (11/15, 73,3%). Cinco (39%) de 13 pacientes com criptocococe do SNC tiveram coinfecções neurológicas. As prevalências de LFA positivo no sangue periférico (19/74) e de criptococose do SNC (13/74) foram de 25,7%; IC 95%, 15,5 a 40,1% e 17,6%; IC 95%, 9,4 a 30,0%, respectivamente. Entre os seis (8,1%) pacientes com LFA positivo no sangue periférico mas negativo no LCR, quatro (5,4%) apresentaram antigenemia criptocócica assintomática isolada, um (1,3%) foi classificado como antigenemia criptocócica sintomática e um (1,3%) apresentou criptococcemia. A mortalidade intra-hospitalar global foi de 20,3% (15/74), e não houve diferença estatisticamente significante entre os pacientes com LFA positivo e negativo em sangue periférico. Conclusão: As prevalências de antigenemia criptocócica e de criptococose do SNC, utilizando LFA no sangue periférico, foram elevadas. A criptococose foi a causa mais frequente de meningoencefalite e apresentou elevada mortalidade intrahospitalar. Finalmente, propomos um algoritmo de manejo no PS para PVHA com sintomas neurológicos
Title in English
Prevalence of cryptococcal antigenemia using lateral flow assay in peripheral blood of PLWHA with advanced disease and neurological symptoms: prospective cohort study in emergency department of tertiary hospital in São Paulo, Brazil
Keywords in English
Acquired immunodeficiency syndrome
Central nervous system
Cryptococcosis
Diagnosis
Emergency medical services
Meningitis cryptococcal
Abstract in English
Introduction: Timely diagnosis is crucial in the management of central nervous system (CNS) cryptococcal infection in people living with HIV/AIDS (PLWHA). The aim of this study was to evaluate the prevalence of cryptococcal antigenemia and CNS cryptococcosis in PLWHA with advanced immunosuppression presenting neurological symptoms, using point-of-care lateral flow assay (LFA) on peripheral blood without the need for laboratory facilities in the emergency department (ED) of a referral center for infectious diseases in São Paulo, Brazil. Additionally, we aimed to describe the main characteristics of this population and propose an initial management algorithm for this patient profile. Methods: A prospective cohort study was conducted in the ED of the Emilio Ribas Institute of Infectious Diseases (IIER) between January and September 2020. All included patients underwent LFA testing on peripheral blood, and those with positive results underwent lumbar puncture for cerebrospinal fluid (CSF) collection and LFA testing on CSF. Diagnostic and therapeutic management of the included cases followed institutional protocols. Results: During the study period, 497 PLWHA were admitted to the IIER ED, of whom 74 (14.9%) were included. The median age (IQR) was 40 (30-48) years, with a predominance of males (62%). The median (IQR) CD4 T-cell count and HIV viral load were 43 (20-130) cells/mL and 36,401 (457-288,055) copies/mL, respectively. All included cases had a prior diagnosis of HIV infection. The median (IQR) time between symptom onset and hospital admission was 15 (6-39) days. The main neurological manifestations were headache (41/74, 55.4%), altered consciousness (35/74, 47.3%), and focal motor deficit (31/74, 41.9%). Cryptococcosis was the most frequent cause of meningoencephalitis (11/15, 73.3%). Five (39%) out of 13 patients with cryptococcal CNS infection had neurological coinfections. The prevalence of positive LFA in peripheral blood (19/74) and CNS cryptococcosis (13/74) were 25.7% (95% CI, 15.5 to 40.1%) and 17.6% (95% CI, 9.4 to 30.0%), respectively. Among the six (8.1%) patients with positive LFA in peripheral blood but negative CSF, four (5.4%) had isolated asymptomatic cryptococcal antigenemia, one (1.3%) was classified as symptomatic cryptococcal antigenemia, and one (1.3%) had cryptococcemia. The overall in-hospital mortality rate was 20.3% (15/74), and there was no statistically significant difference between patients with positive and negative LFA in peripheral blood. Conclusion: The prevalence of cryptococcal antigenemia and CNS cryptococcosis, using LFA on peripheral blood, was high. Cryptococcosis was the most frequent cause of meningoencephalitis and had a high in-hospital mortality rate. Finally, we propose an ED management algorithm for PLWHA with neurological symptoms
 
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Publishing Date
2023-11-24
 
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