Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection.

BACKGROUND: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection. METHODS: We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks. RESULTS: Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients. CONCLUSION: HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.

Transplant-associated Ochroconis gallopava infections.

BACKGROUND: Ochroconis gallopava is a neurotropic dematiaceous mold that causes respiratory and central nervous system (CNS) infection in domestic poultry and in immunocompromised patients. We recently treated 3 solid organ transplant (SOT) recipients for pulmonary Ochroconis infections with successful outcome, prompting us to review the literature on this unique pathogen. METHODS: We reviewed all published cases of O. gallopava infections in SOT recipients and analyzed the impact of CNS infection on the outcome. RESULTS: In addition to the 3 new cases reported here, 9 published cases of Ochroconis infection were analyzed. The disease involved the lungs only in 5/12 (42%) of patients, brain in 6/12 (50%) patients, and lung and skin in 1 patient. Survival was significantly reduced with brain infection (33% vs. 100%; P<0.03; Fisher's exact test). CONCLUSIONS: O. gallopava may infect SOT recipients with a particular tropism for the CNS. Early recognition of O. gallopava pulmonary infection is important, as the prognosis is excellent before dissemination to the brain.

Control, immunoregulation, and expression of innate pulmonary host defenses against Aspergillus fumigatus.

The innate host defense system (IHDS) against Aspergillus fumigatus includes dedicated phagocytic cells (peripheral blood monocytes, monocyte derived macrophages, pulmonary alveolar macrophages, neutrophils, myeloid dendritic cells and natural killer cells), cytokines, chemokines, toll-like receptors, and antimicrobial peptides. During the past decade, the advances in the field of the IHDS have been enormous, allowing a better understanding of the immunopharmacological control, immunoregulation, and expression of innate host defense molecules against Aspergillus fumigatus.

Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation.

Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation were given respiratory syncytial virus (RSV) immune globulin (RSVIG) at the time of transplantation and again 3 weeks later. Antibody titers to RSV, human parainfluenza virus 3, measles, and influenza H1N1, H3N2, and B were measured prior to administration of RSVIG and 6 more times over the course of the subsequent 6 weeks. Baseline antiviral titers and increases in antibody after administration of RSVIG were extremely variable for all the viruses. In 18 patients in whom the baseline titers of antibody titers to RSV-F protein were 1:640-1:2048, there was a 7.7-fold initial increase in these titers after the first dose of RSVIG, compared with a 2.1-fold increase in 14 patients with baseline titers of 1:4096-1:20,840; increases in titers of antibody against the other viruses after the first dose of RSVIG reflected similar variability. The subset of patients with the lowest titers appear to receive the greatest benefit from administration of RSVIG.

High-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation.

We evaluated high-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation. One hundred and seventy-four consecutive patients who were at risk for CMV infection (either recipient or donor seropositive) and received either intensive chemoradiotherapy and a T cell-depleted stem cell transplant followed by delayed add-back of donor T cells (TCDT: n = 98), or a non-myeloablative preparative regimen followed by an unmanipulated peripheral blood stem cell transplant (NMT: n = 76) from an HLA-identical sibling donor were studied. All received high-dose acyclovir (HDACV) from day - 7 for 3 months post-transplant in conjunction with weekly CMV pp65 antigenemia monitoring and pre-emptive treatment with intravenous immunoglobulin (not CMV-specific) and ganciclovir. The actuarial probabilities of developing pp65 antigenemia were 83 +/- 4% after TCDT and 41 +/- 6% after NMT (P < 0.00001) with reactivation occurring earlier in the TCDT group (the median 36 days vs 55 days). We observed no reactivation of CMV in seronegative recipients with a seropositive donor (n = 23). A total of 11 patients (5 in TCDT, 6 in NMT) developed CMV disease within 400 days after transplantation, and one death was clearly attributable to CMV interstitial pneumonitis (IP). This strategy was associated with effective control of CMV antigenemia in the majority of patients and near-complete eradication of fatal CMV IP.

Outbreak of human parainfluenza virus 3 infections in a hematopoietic stem cell transplant population.

Clinical manifestations and epidemiological features are described for a cluster of 12 cases of human parainfluenza virus 3 (HPIV3) infection that occurred among 64 allogeneic hematopoietic stem cell transplant (SCT) recipients in an 11-week period during spring 2000. Upper respiratory symptoms predominated. Pneumonia occurred in 3 patients and was a contributing factor in the death of 1 patient. Exposure histories and molecular analysis of HPIV3 isolates suggested that both community acquired and nosocomially transmitted infections occurred during this outbreak. A chain of transmission within the outpatient clinic appeared to have occurred in 4 outpatients and to have extended to 2 hospitalized patients. Molecular epidemiology was useful in discerning routes of transmission in this outbreak.

Hypercalcemia and T-cell lymphoma with acquired immunodeficiency syndrome: occurrence without human T-cell leukemia virus-I.

We describe the case of a patient with acquired immunodeficiency syndrome (AIDS) who had a CD4 cell count of 60/microL, bilateral hilar adenopathy, and hypercalcemia. Transbronchial biopsy showed T-cell anaplastic large cell lymphoma. Serology was negative for human T-cell leukemia virus-I (HTLV-I). This appears to be the first case of T-cell anaplastic large cell lymphoma occurring in an AIDS patient with hypercalcemia who was seronegative for HTLV-I.

In utero sonographic diagnosis of vesicoureteral reflux by percutaneous vesicoinfusion.

Vesicoureteral reflux affects approximately 1% of newborns. Although most affected children show only sonographic evidence of renal pelvic dilatation, others may show overt hydronephrosis, indistinguishable from that seen in fetuses with obstructive uropathy. Hydronephrosis secondary to fetal vesicoureteral reflux cannot be differentiated on ultrasound examination from that resulting from lower obstructive uropathy with or without reflux. As renal damage from vesicoureteral reflux may occur in up to 70% of cases, early identification and possible in utero treatment of these fetuses may be warranted. We report a sonographic technique, vesicoinfusion, for diagnosis of vesicoureteric reflux in utero. The accurate identification of vesicoureteral reflux in utero may have important diagnostic, prognostic and therapeutic implications.