Rafi F. Dauar

Strategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin America

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.

BK virus associated meningoencephalitis in an AIDS patient treated with HAART

A severely immune-suppressed AIDS patient was suspected of suffering from BK virus (BKV) meningoencephalitis, after being studied for common causes of neurological complications of co-infectious origin. Polymerase chain reaction (PCR) and sequence analysis of cerebrospinal fluid and brain samples, confirmed the presence of BKV. His clinical condition improved along with the regression of brain lesions, after modifications on his antiretroviral regime. Five months after discharge, the patient was readmitted because of frequent headaches, and a marked inflammatory reaction was evidenced by a new magnetic resonance imaging (MRI). The symptoms paralleled a rising CD4+ lymphocyte count, and immune reconstitution syndrome was suspected. This is the first non-postmortem report of BKV meningoencephalitis in an AIDS patient, showing clinical and radiographic improvement solely under HAART.

Role of quantitative CSF microscopy to predict culture status and outcome in HIV-associated cryptococcal meningitis in a Brazilian cohort

This retrospective study aimed to evaluate the clinical, laboratory, and quantitative cerebrospinal fluid (CSF) cryptococcal cell counts for associations with in-hospital outcomes of HIV-infected patients with cryptococcal meningitis. Ninety-eight HIV-infected adult patients with CSF culture-proven cryptococcal meningitis were admitted between January 2006 and June 2008 at a referral center in Sao Paulo, Brazil. Cryptococcal meningitis was the first AIDS-defining illness in 69%, of whom 97% (95/98) had known prior HIV infection. The median CD4+ T-cell count was 39 cells/μL (interquartile range 17-87 cells/μL). Prior antiretroviral therapy was reported in 50%. Failure to sterilize the CSF by 7-14 days was associated with baseline fungal burden of ≥ 10 yeasts/μL by quantitative CSF microscopy (odds ratio [OR] = 15.3, 95% confidence interval [CI] 4.1-56.7; P < 0.001) and positive blood cultures (OR = 11.5, 95% CI 1.2-109; P = 0.034). At 7-14 days, ≥ 10 yeasts/μL CSF was associated with positive CSF cultures in 98% versus 36% with <10 yeasts/μL CSF (P < 0.001). In-hospital mortality was 30% and was associated with symptoms duration for >14 days, altered mental status (P < 0.001), CSF white blood cell counts <5 cells/μL (P = 0.027), intracranial hypertension (P = 0.011), viral loads >50,000 copies/mL (P = 0.036), ≥ 10 yeasts/μL CSF at 7-14 days (P = 0.038), and intracranial pressure >50 cmH(2)0 at 7-14 days (P = 0.007). In conclusion, most patients were aware of their HIV status. Fungal burden of ≥ 10 yeasts/μL by quantitative CSF microscopy predicted current CSF culture status and may be useful to customize the induction therapy. High uncontrolled intracranial pressure was associated with mortality.

Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture-proven case reported in Brazil.

Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV) infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT) showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.

CEREBRAL TUBERCULOMAS IN AIDS PATIENTS A forgotten diagnosis

The human immunodeficiency virus (HIV) infection epidemics increased the prevalence, multi-drug resistance and disseminated forms of tuberculosis. The central nervous system (CNS) tuberculosis has high mortality and morbidity, and it is usually divided into diffuse (meningitis) and localized (tuberculoma and abscess) forms. We report three cases of cerebral tuberculomas in AIDS patients: one with definitive diagnosis, confirmed with histopathology, and two with probable diagnosis, based on clinical information, radiological images, Mycobaterium tuberculosis isolation out of the CNS and adequate response to antituberculous treatment. Further, we discuss diagnostic, therapeutic and prognostic issues of tuberculomas, with emphasis in the distinction from cerebral tuberculous abscesses. Despite of their infrequent presentation, tuberculomas should be considered in the differential diagnosis of cerebral expansive lesions in patients with AIDS.

Importance of high IgG anti-Toxoplasma gondii titers and PCR detection of T. gondii DNA in peripheral blood samples for the diagnosis of AIDS-related cerebral toxoplasmosis: a case-control study

BACKGROUND Cerebral toxoplasmosis (CT) continues to cause significant morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in Brazil. In clinical practice, the initial diagnosis is usually presumptive and alternative diagnosis tools are necessary. Our objective was to evaluate whether the detection of high titers of IgG anti-Toxoplasma gondii and T. gondii DNA in blood samples are associated with the diagnosis of CT. METHODS In this case-control study we included 192 patients with HIV-1 infection: 64 patients with presumptive CT (cases) and 128 patients with other diseases (controls). Blood samples to perform indirect immunofluorescense reaction (IFI) to detect anti-T. gondii IgG antibodies and polymerase chain reaction (PCR) were collected before or within the first three days of anti-Toxoplasma therapy. Two multivariate logistic regression models were performed: one including the variable qualitative serology and another including quantitative serology. RESULTS In the first model, positive IgG anti-T. gondii (OR 4.7, 95% CI 1.2-18.3; p = 0.027) and a positive T. gondii PCR result (OR 132, 95% CI 35-505; p < 0.001) were associated with the diagnosis. In the second model, IgG anti-T. gondii titres > 1:1024 (OR 7.6, 95% CI 2.3-25.1; p = 0.001) and a positive T. gondii PCR result (OR 147, 95% CI 35-613; p < 0.001) were associated with the diagnosis. CONCLUSIONS Quantitative serology and molecular diagnosis in peripheral blood samples were independently associated with the diagnosis of CT in HIV-infected patients. These diagnostic tools can contribute to a timely diagnosis of CT in settings where Toxoplasma infection is common in the general population.

Cerebral mass lesion due to cytomegalovirus in a patient with AIDS: case report and literature review.

Cytomegalovirus (CMV) disease in acquired immunodeficiency syndrome (AIDS) patients most commonly presents as chorioretinitis and gastro-intestinal infection. Neurological involvement due to CMV may cause several clinical presentations: polyradiculitis, myelitis, encephalitis, ventriculo-encephalitis, and mononeuritis multiplex. Rarely, cerebral mass lesion is described. We report a 39 year-old woman with AIDS and previous cerebral toxoplasmosis. She presented with fever, seizures, and vulval ulcers. Her chest X-ray showed multiple lung nodules, and a large frontal lobe lesion was seen in a brain computed tomography scan. She underwent a brain biopsy through a frontal craniotomy, but her condition deteriorated and she died in the first postoperative day. Histopathological studies and immunohistochemistry disclosed CMV disease, and there was no evidence of cerebral toxoplasmosis, bacterial, mycobacterial or fungal infection. CMV disease should be considered in the differential diagnosis of cerebral mass lesion in AIDS patients. High suspicion index, timely diagnostic procedures (surgical or minimally invasive), and proper utilization of prophylactic and therapeutic medication could improve outcome of these patients.

Ring enhancing intracranial lesion responding to antituberculous treatment in an HIV-infected patient

Cerebral tuberculomas constitute a major differential diagnosis of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected patients in developing countries. We report the case of a 34-year old woman co-infected with HIV and possible disseminated tuberculosis (hepatitis, lymphadenopathy, and pleural effusion) who presented a large and solitary intracranial mass lesion. Despite extensive diagnostic efforts, including brain, ganglionar, and liver biopsies, no definitive diagnosis was reached. However, a trial with first-line antituberculous drugs led to a significant clinical and radiological improvement. Atypical presentations of cerebral tuberculomas should always be considered in the differential diagnosis of intracranial mass lesions in HIV-infected patients and a trial with antituberculous drugs is a valuable strategy to infer the diagnosis in a subset of patients.