ABSTRACT
SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcusspecies. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.
RESUMOA meningite criptocócica continua causando um substancial índice de óbitos em pacientes infectados por HIV em países de baixa e média renda. Ferramentas diagnósticas para detecção do antígeno capsular polissacarídico criptocócico (CrAg) em soro e líquor tais como o teste de aglutinação de látex (latex-CrAg) ou o imunoensaio (EIE) têm sido utilizadas por muitos anos. Técnicas diagnósticas mais aprimoradas seriam cruciais nas fases assintomática e sintomática da criptococose para reduzir a mortalidade. Recentemente, o ensaio de fluxo lateral para detecção do antígeno criptocócico (LFA CrAg) foi incluído no arsenal diagnóstico. Contrariamente aos outros testes, LFA CrAg é um ensaio imunocromatográfico em formato similar ao teste de gravidez, e requer pouca ou nenhuma infraestrutura laboratorial. Este teste preenche os critérios ASSURED (Affordable, Sensitive,Specific, User friendly,Rapid/ robust,Equipment-free,Delivered) da Organização Mundial da Saúde e pode ser utilizado em soro, plasma, sangue total ou líquor para o diagnóstico da criptococose. LFA CrAg tem melhor sensibilidade analítica para o C. gattii que o teste de látex-CrAg ou EIE. A prevenção da doença criptocócica constituiria uma nova aplicação do LFA CrAg, mediante a triagem de amostras de sangue para a identificação de infecção sub-clínica em pacientes infectados pelo HIV que não apresentam sintomas, possuem contagem de CD4 < 100 células/mL e não recebem terapia antirretroviral eficaz. A triagem de CrgA em amostras de plasma remanescente da contagem de CD4 pode identificar pacientes com infecção assintomática que precisam urgentemente de tratamento preemptivo com fluconazol, evitando assim a progressão para doença sintomática e/ou óbito.
Subject(s)
Humans , AIDS-Related Opportunistic Infections/diagnosis , Antigens, Fungal/immunology , Cryptococcus/immunology , Meningitis, Cryptococcal/diagnosis , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/mortality , Antigens, Fungal/blood , Chromatography, Affinity , Meningitis, Cryptococcal/blood , Meningitis, Cryptococcal/mortality , Point-of-Care Systems , Sensitivity and SpecificityABSTRACT
This study compared clinical manifestations, blood biochemistry and cerebrospinal fluid (CSF) results of HIV-positive and HIV-negative patients with cryptococcal meningitis. We collected 57 cases of cryptococcal meningitis from cytological specimens submitted to the Department of Tropical Pathology, Faculty of Tropical Medicine. Pertinent clinical data were analyzed retrospectively in 47 cases for clinical manifestations, laboratory features and outcomes of 38 HIV-positive and 9 HIV-negative patients. Headache was the most common symptom seen in all cases, of which 70.2% occurred with fever. CSF examination of both groups revealed elevated opening pressure. Increased CSF protein and depressed CSF glucose levels were seen in HIV-negative cases, which differed from HIV-positive cases, where a slight change was noted. CSF pleocytosis in HIV-positive patients was variable. Forty-eight percent of HIV-positive patients had CSF leukocyte counts below 20 cells/ mm3. None was found in the HIV-negative patients. Specific treatments with amphotericin B and fluconazole were given. Five fatal cases of cryptococcal meningitis were noted, all of which were HIV-positive. There were statistically significant differences in blood neutrophils, blood eosinophils, CSF leukocyte counts, CSF neutrophils, CSF lymphocytes, CSF glucose, and CSF total protein, in HIV-positive and HIV-negative patients (p = 0.050, p = 0.022, p = 0.002, p = 0.016, p = 0.047, p = 0.031, p = 0.009, respectively).
Subject(s)
Adolescent , Adult , Chi-Square Distribution , Female , HIV Seronegativity , HIV Seropositivity , Humans , Male , Meningitis, Cryptococcal/blood , Middle Aged , Retrospective Studies , Statistics, Nonparametric , Thailand/epidemiologyABSTRACT
La criptococosis es una micosis oportunista producida por la levadura capsulada Cryptococcus neoformans, que se observa cada vez con más frecuencia; la variedad clínica más común es la meningitis y se asocia sobre todo con pacientes de SIDA (95 por ciento). El diagnóstico de laboratorio de ser integral, las pruebas más útiles son: examen en fresco con tinta china y tinción de resaltado capsular; los medios de cultivo rutinarios para su aislamiento son el Sabouraud y el agar alpiste negro (Niger o Staib), es necesaria la identificación posterior de la cepa por medios bioquímicos (auxonograma y zimograma). La prueba inmunológica más efectiva para diagnóstico y monitoreo terapéutico es la determinación de antígeno criptococósico por aglutinación directa con partículas de látex (DACAD). El pronóstico del padecimiento es malo, y el mejor exquema de tratamiento es a base de anfotericina B más fluconazol
Subject(s)
Humans , Amphotericin B/therapeutic use , Biopsy , Cerebrospinal Fluid , Clinical Laboratory Techniques , Cryptococcosis/diagnosis , Cryptococcosis/epidemiology , Cryptococcosis/physiopathology , Meningitis, Cryptococcal/cerebrospinal fluid , Meningitis, Cryptococcal/bloodABSTRACT
The results of an open study of the efficacy of oral itraconazole therapy in 8 patients with cryptococcal meningitis are reported. Therapy is monitored by clinical response with culture, indian ink stain and cryptococcal antigen testing of CSF. Four (50%) of eight patients were cured, two (25%) had partial response, and two (25%) failed. One patient had a relapse but responded to retreatment. No toxicity was observed. Itraconazole is, therefore, suggested as a new treatment for cryptococcal meningitis.