Corina E. Gonzalez

Invasive aspergillosis in human immunodeficiency virus-infected children

BACKGROUND Aspergillosis is an uncommon yet serious opportunistic infection in patients with AIDS. It has been extensively reported in HIV-infected adult patients. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of aspergillosis in a large HIV-infected pediatric population. METHODS We reviewed the records of all 473 HIV-infected children followed in the Pediatric Branch of the National Cancer Institute for 9 years from 1987 through 1995 for the presence of Aspergillus infection. RESULTS Seven (1.5%) patients developed invasive aspergillosis during the study period. All patients had low CD4 counts reflecting severe immunosuppression. Sustained neutropenia (> 7 days) or corticosteroid therapy as a predisposing factor for invasive aspergillosis was encountered in only two patients (28%). Invasive pulmonary aspergillosis developed in five patients and cutaneous aspergillosis in two. The most common presenting features in patients with pulmonary aspergillosis were fever, cough and dyspnea. Patients with cutaneous aspergillosis were diagnosed during life and successfully treated with amphotericin B and surgery, whereas diagnosis of pulmonary aspergillosis was made clinically in only one patient. CONCLUSIONS Aspergillosis is an uncommon but highly lethal opportunistic infection in HIV-infected children. Invasive pulmonary aspergillosis should be considered in the differential diagnosis in febrile, HIV-infected children with persistent pulmonary infiltrates.

Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical manifestations and risk factors.

Background. Littleis known about the epidemiology and clinical features of esophageal candidiasis (EC) in pediatric AIDS. We therefore investigated the clinical presentation and risk factors of EC in a large prospectively monitored population of HIV-infected children at the National Cancer Institute. Patients and methods. We reviewed the records of all HIV-infected children (N = 448) followed between 1987 and 1995 for a history of esophageal candidiasis to characterize the epidemiology, clinical features, therapeutic interventions and outcome of esophageal candidiasis. To understand further the risk factors for EC in pediatric AIDS, we then performed a matched case-control analysis of 25 patients for whom control cases were available. Results. There were 51 episodes of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17 years; median CD4, count 11/&mgr;l), representing a frequency of EC of 8.0%. Concurrent oropharyngeal candidiasis (OPC) was the most common clinical presentation of EC (94%); other signs and symptoms included odynophagia (80%), retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%), dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%) or itraconazole (1%). A clinical response was documented in all 45 evaluable episodes. In 6 other cases, EC was a final event without contributing to the cause of death. By a conditional logistic regression model for matched data, the best predictor of EC was the presence of prior OPC (P < 0.0001), followed by CD4 count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P = 0.0013). The risks associated with low CD4 count were independent of that of prior OPC. Conclusion. EC in pediatric AIDS is a debilitating infection, which develops in the setting of prior OPC, low CD4 counts and previous antibiotics.

Lymphoid interstitial pneumonitis in pediatric AIDS. Natural history of the disease.

Lymphoid interstitial pneumonitis (LIP), as well as other conditions characterized by abnormal lymphoid proliferation, has been described with increased frequency in patients with HIV infection. Lymphoid interstitial pneumonitis is particularly common in pediatric AIDS and has been reported in up to 40% of vertically infected infants and children with pulmonary disease.1–4 Although it is known that LIP can cause significant morbidity, the natural history and pathogenesis of this condition are not well understood. Recent advances in the understanding of the pathogenesis of interstitial lung disease suggest that it may be a cytokine-mediated process, the initiation and perpetuation of which is dependent on immune responses to HIV antigens and direct effects of HIV and/or other pathogens such as EpsteinBarr virus (EBV).5,6 The natural history of pediatric HIV infection is that of a progressive disease leading to profound immunosuppression with continuous viral replication.7,8 This process entails changes in the host immunity that can definitely affect the course of lymphoid proliferations. Similarly, antiretroviral therapy, particularly highly active antiretroviral therapy (HAART), can also affect the course of these conditions. Because HIV-infected patients survive longer as a result of improved antiretroviral therapy and supportive care, long-term studies on the course of LIP and other lymphoid interstitial disorders (LPDs) are now possible.

Impact of chemotherapy for AIDS-related malignancies in pediatric HIV disease.

Children with the acquired immunodeficiency syndrome (AIDS) are at increased risk of developing a malignancy. Non-Hodgkin’s lymphoma (NHL) and Kaposi’s sarcoma are the most common malignancies associated with AIDS. Treatment of these conditions requires chemotherapy to effect disease control or cure. Chemotherapy, however, has been associated with profound and repetitive periods of myelosuppression as well as with infectious complications, which may be poorly tolerated by patients with AIDS. There is a paucity of information regarding the impact of chemotherapy on HIV disease, particularly on viral replication and immunity. The literature in pediatric AIDS is limited to case reports or short case series. In general, these studies show poor response rates to chemotherapy and short survival times, which may indicate that chemotherapy has a profound deleterious effect on HIV disease.1–4