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      FEVER OF UNDETERMINED ORIGIN IN PATIENTS WITH THE ACQUIRED IMMUNODEFICIENCY SYNDROME IN BRAZIL: REPORT ON 55 CASES Translated title: Febre de origem indeterminada em pacientes com a síndrome da imunodeficiência adquirida no Brasil: relato de 55 casos

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          Abstract

          The medical records of patients with AIDS admitted to a general hospital in Brazil from 1989 to 1997 were reviewed retrospectively with the aim at defining the frequency and etiology of fever of undetermined origin (FUO) in HIV-infected patients of a tropical country and to evaluate the usefulness of the main diagnostic procedures. 188 (58.4%) out of 322 patients reported fever at admission to hospital and 55 (17.1%) had FUO. Those with FUO had a mean CD4+ cell count of 98/ml. A cause of fever was identified for 45 patients (81.8%). Tuberculosis (32.7%), Pneumocystis carinii pneumonia (10.9%), and Mycobacterium avium complex (9.1%) were the most frequent diagnoses. Other infectious diseases are also of note, such as cryptococcal meningitis (5.5%), sinusitis (3.6%), Salmonella-S. mansoni association (3.6%), disseminated histoplasmosis (3.6%), neurosyphilis (1.8%), and isosporiasis (1.8%). Four patients had non-Hodgkin's lymphoma (7.3%). We conclude that an initial aggressive diagnostic approach should be always considered because biopsies (lymph node, liver and bone marrow) produced the highest yield in the diagnosis of FUO and the majority of the diagnosed diseases are treatable. The association of diseases is common and have contributed to delay the final diagnosis of FUO in most cases. In our study area the routine request of hemocultures for Salmonella infection and the investigation of cryptococcal antigen in the serum should be considered.

          Translated abstract

          Revisaram-se os prontuários médicos de pacientes com AIDS e febre de origem indeterminada (FOI) com o objetivo de definirem-se as causas de FOI em indivíduos HIV positivos em um país tropical e, ainda, determinar o valor dos procedimentos diagnósticos mais utilizados. Cento e oitenta e oito (58,4%) de 322 pacientes apresentavam febre à internação e 55 (17,1%) preencheram os critérios de FOI. A contagem média de CD4+ no grupo com FOI era de 98 células/ml. Definiu-se a causa da febre em 45 pacientes (81,8%). As seguintes doenças infecciosas predominaram como causa de FOI: Tuberculose (32,7%), pneumonia pelo Pneumocystis carinii (10,9%) e Mycobacterium avium complex (9,1%). Outras doenças infecciosas merecem destaque: meningite criptocócica (5,5%), sinusite (3,6%), associação Salmonella-S. mansoni (3,6%), histoplasmose disseminada (3,6%), neuro-sífilis (1,8%) e isosporíase (1,8%). No grupo das neoplasias, quatro pacientes (7,3%) apresentaram linfomas não-Hodgkin disseminados. As biópsias de linfonodos, de fígado e de medula óssea responsabilizaram-se pelo maior número de diagnósticos definitivos na presente casuística. A associação de doenças mostrou-se comum e atrasou o diagnóstico da febre na maioria dos casos. Em nossa região, a realização rotineira de hemoculturas visando identificar os indivíduos com salmonelose prolongada associada à esquistossomose e a pesquisa de antígeno circulante para Cryptococcus neoformans devem ser consideradas nos pacientes com AIDS e FOI.

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          Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature.

          Histoplasmosis is a serious opportunistic infection in patients with AIDS, often representing the first manifestation of the syndrome. Most infections occurring within the endemic region are caused by exogenous exposure, while those occurring in nonendemic areas may represent endogenous reactivation of latent foci of infection or exogenous exposure to microfoci located within those nonendemic regions. However, prospective investigations are needed to prove the mode of acquisition. The infection usually begins in the lungs even though the chest roentgenogram may be normal. Clinical findings are nonspecific; most patients present with symptoms of fever and weight loss of at least 1 month's duration. When untreated, many cases eventually develop severe clinical manifestations resembling septicemia. Chest roentgenograms, when abnormal, show interstitial or reticulonodular infiltrates. Many cases have been initially misdiagnosed as disseminated mycobacterial infection or Pneumocystis carinii pneumonia. Patients are often concurrently infected with other opportunistic pathogens, supporting the need for a careful search for co-infections. Useful diagnostic tests include serologic tests for anti-H. capsulatum antibodies and HPA, silver stains of tissue sections or body fluids, and cultures using fungal media from blood, bone marrow, bronchoalveolar lavage fluid, and other tissues or body fluids suspected to be infected on clinical grounds. Treatment with amphotericin B is highly effective, reversing the clinical manifestations of infection in at least 80% of cases. However, nearly all patients relapse within 1 year after completing courses of amphotericin B of 35 mg/kg or more, supporting the use of maintenance treatment to prevent recurrence. Relapse rates are lower (9 to 19%) in patients receiving maintenance therapy with amphotericin B given at doses of about 50 mg weekly or biweekly than with ketoconazole (50-60%), but controlled trials comparing different maintenance regimens have not been conducted. Until results of such trials become available, our current approach is to administer an induction phase of 15 mg/kg of amphotericin B given over 4 to 6 weeks, followed by maintenance therapy with 50 to 100 mg of amphotericin B given once or twice weekly, or biweekly. If results of a prospective National Institutes of Allergy and Infectious Disease study of itraconazole maintenance therapy document its effectiveness, alternatives to amphotericin B may be reasonable.
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            Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome.

            We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital. We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis. In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS. Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40). Flucytosine had to be discontinued in over half the patients because of cytopenia. Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs. 141 days; P less than 0.004). The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source. The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively). From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.
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              Tuberculous meningitis in patients infected with the human immunodeficiency virus.

              Tuberculosis is a frequent complication of human immunodeficiency virus (HIV) infection. We describe the clinical manifestations and outcomes of tuberculous meningitis in patients with HIV infection, and compare them with those in non-HIV-infected patients. We reviewed the records from 1985 through 1990 at two large referral hospitals in Madrid for patients who had Mycobacterium tuberculosis isolated from cerebrospinal fluid. Of 2205 patients with tuberculosis, 455 (21 percent) also had HIV infection, of whom 45 had M. tuberculosis isolated from the cerebrospinal fluid. Of the 37 HIV-infected patients with tuberculous meningitis for whom records were available, 24 (65 percent) had clinical or radiologic evidence of extrameningeal tuberculosis at the time of admission. In 18 of 26 patients (69 percent), a CT scan of the head was abnormal. In most patients, analysis of cerebrospinal fluid showed pleocytosis (median white-cell count, 0.234 x 10(9) per liter) and hypoglycorrhachia (median glucose level, 1.3 mmol per liter), but in 43 percent (15 of 35), the level of protein in cerebrospinal fluid was normal. In four patients with HIV infection, tuberculosis was only discovered after their deaths. Of the 33 patients who received antituberculous treatment, 7 died (in-hospital mortality, 21 percent). Illness lasting more than 14 days before admission and a CD4+ cell count of less than 0.2 x 10(9) per liter (200 per cubic millimeter) were associated with a poor prognosis. Comparison with tuberculous meningitis in patients without HIV infection showed that the presentation, clinical manifestations, cerebrospinal fluid findings, and mortality were generally similar in the two groups. However, of the 1750 patients without HIV infection, only 2 percent (38 patients) had tuberculous meningitis, as compared with 10 percent of the HIV-infected patients (P less than 0.001). HIV-infected patients with tuberculosis are at increased risk for meningitis, but infection with HIV does not appear to change the clinical manifestations or the outcome of tuberculous meningitis.
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                Author and article information

                Journal
                rimtsp
                Revista do Instituto de Medicina Tropical de São Paulo
                Rev. Inst. Med. trop. S. Paulo
                Instituto de Medicina Tropical (São Paulo, SP, Brazil )
                1678-9946
                January 1999
                : 41
                : 1
                : 27-32
                Affiliations
                [01] orgnameUFMG orgdiv1 Departamento de Clínica Médica, Faculdade de Medicina Brasil
                Article
                S0036-46651999000100006 S0036-4665(99)04100106
                10.1590/S0036-46651999000100006
                c61c85b1-a980-41c0-9e8b-632d3c3ba5df

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 23 June 1998
                : 16 December 1998
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 27, Pages: 6
                Product

                SciELO Brazil

                Categories
                AIDS

                Fever of undetermined origin,Fever,Acquired immunodeficiency syndrome,AIDS,Fever of unknown origin

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