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.

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.

A doença meningocócica invasiva (DMI) é um problema de saúde pública e continua causando importante mortalidade e morbidade. O sorotipo C é o mais frequente no Brazil. O espectro clínico da DMI é amplo (meningite, meningococcemia ou ambos) e a evolução clínica pode ser imprevisível. As principais características associadas a mortalidade são: idade acima de 50 anos, convulsões, choque, e meningococcemia sem meningite. Culturas de sangue devem ser obtidas imediatamente. Punção lombar pode ser realizada sem tomografia computadorizada (TC) prévia na maioria dos casos. Características clínicas podem ajudar a predizer pacientes com elevada probabilidade de apresentar TC alterada. Cultura e Gram no líquido cefalorraquiano devem ser sempre solicitadas. Aglutinação do látex apresenta sensibilidade muito variável. Reação em cadeia da polimerase é especialmente útil quando os outros métodos são negativos ou demorados. O uso de ceftriaxona não deve ser retardado enquanto se esperam os resultados do líquor ou TC. Dexametasona pode ser utilizada na meningite meningococóca. Suspeita precoce de DMI, antibiótico no primeira atendimento, antes da admissão hospitalar, transporte rápido para hospital, e estabilização em unidade de terapia intensiva reduz substancialmente a taxa de letalidade. Vacinas contra os sorotipos A, C, W-135, e Y estão disponíveis, entretanto, vacinas contra o sorotipo B são esperadas.

Invasive meningococcal disease (IMD) is a major public health and continues to cause substantial mortality and morbidity. Serotype C is the most frequent in Brazil. The clinical spectrum of IMD is broad (meningitis, meningococcemia or both) and the clinical evolution may be unpredictable. Main features associated with mortality are: age higher than 50 years old, seizures, shock, and meningococcemia without meningitis. Blood cultures should be obtained immediately. Lumbar puncture can be performed without previous computed tomography scan (CT) in most cases. Clinical features can be useful to predic patients where an abnormal CT scan is likely. Cerebrospinal fluid (CSF) culture and Gram stain should always be required. Latex agglutination sensitivity is highly variable. Polymerase chain reaction is specially useful when other methods are negative or delayed. Usually ceftriaxone should not be delayed while awaiting CSF study or CT. Dexamethasone can be used in meningococcal meningitis. Early suspicion of IMD and antibiotic in primary care before hospitalization, rapid transportation to a hospital, and stabilization in an intensive-care unit has substantially reduced the case-fatality rate. Vaccines against serotypes A, C, W-135, and Y are available while vaccines against serotype B are expected.

Latin America is the region with the third most AIDS-related cryptococcal meningitis infections globally. Highly active antiretroviral therapy (HAART) has reduced the number of infections; however, the number of deaths and the case-fatality rate continues to be unacceptable. In this review, we focus on the burden of AIDS-related cryptococcosis in Latin America and discuss potential strategies to reduce early mortality from Cryptococcus. In this review, we highlight the importance of: (1) earlier HIV diagnosis and HAART initiation with retention-in-care to avoid AIDS; (2) pre-HAART cryptococcal antigen (CRAG) screening with preemptive fluconazole treatment; (3) better diagnostics (e.g. CRAG testing); and (4) optimal treatment with aggressive management of intracranial pressure and induction therapy with antifungal combination. Implementation of these strategies can reduce cryptococcal-related deaths, improve care, and reduce healthcare costs.

Information about resistance profile of darunavir (DRV) is scarce in Brazil. Our objectives were to estimate the prevalence of DRV resistance mutations in patients failing protease inhibitors (PI) and to identify factors associated with having more DRV resistance mutations. All HIV-infected patients failing PI-based regimens with genotyping performed between 2007 and 2008 in a referral teaching center in São Paulo, Brazil, were included. DRV-specific resistance mutations listed by December 2008 IAS-USA panel update were considered. Two Poisson regression models were constructed to assess factors related to the presence of more DRV resistance mutations. A total of 171 HIV-infected patients with available genotyping were included. The number of patients with lopinavir, saquinavir, and amprenavir used in previous regimen were 130 (76%), 83 (49%), and 35 (20%), respectively. The prevalence of major DRV resistance mutations was 50V: 5%; 54M: 1%; 76V: 4%; 84V: 15%. For minor mutations, the rates were 11I: 3%; 32I: 7%; 33F: 23%; 47V: 6%; 54L: 6%; 74P: 3%; 89V: 6%. Only 11 (6%) of the genotypes had > 3 DRV resistance mutations. In the clinical model, time of HIV infection of > 10 years and use of amprenavir were independently associated with having more DRV resistance mutations. In the genotyping-based model, only total number of PI resistance mutations was associated with our outcome. In conclusion, the prevalence of DRV mutations was low. Time of HIV infection, use of amprenavir and total number of PI resistance mutations were associated with having more DRV mutations.

Recentemente, a reagudização da doença de Chagas (meningoencefalite e/ou miocardite) foi incluída na lista de doenças indicativas de aids no Brasil. Os autores relatam o caso de um paciente de 52 anos de idade, natural de área rural da Bahia e procedente de uma área urbana de São Paulo, sem história de doenças prévias e que apresentou meningoencefalite aguda. As sorologias e pesquisas parasitológicas diretas no sangue e no liquido cefalorraquideano (LCR) demonstraram presença de Trypanosoma cruzi, confirmando-se o diagnóstico mediante cultura do LCR. O teste rápido assim como os ELISA e Western Blot diagnosticaram infecção pelo vírus da imunodeficiência humana (HIV). Apesar do tratamento com benzonidazole e as medidas de suporte, o paciente faleceu 24 horas depois da admissão hospitalar. Em áreas endêmicas, a reagudização da doença de Chagas deve ser sempre considerada no diagnóstico diferencial das meningoencefalites e sua presença em pacientes com infecção pelo HIV é indicativa de aids.

Recently, reactivation of Chagas disease (meningoencephalitis and/or myocarditis) was included in the list of AIDS-defining illnesses in Brazil. We report a case of a 52-year-old patient with no history of previous disease who presented acute meningoencephalitis. Direct examination of blood and cerebrospinal fluid (CSF) showed Trypanosoma cruzi. CSF culture confirmed the diagnosis. Serological assays for T. cruzi and human immunodeficiency virus (HIV) were positive. Despite treatment with benznidazol and supportive measures, the patient died 24 hours after hospital admission. In endemic areas, reactivation of Chagas disease should always be considered in the differential diagnosis of meningoencephalitis among HIV-infected patients, and its presence is indicative of AIDS.