Extrapulmonary and Disseminated Infections Due to Mycobacterium malmoense: Case Report and Review

Mycobacterium malmoense is a potentially pathogenic species that was first described in 1977. During the past decade M. malmoense has been recognized with increasing frequency as a pulmonary pathogen. More than 180 cases of M. malmoense infection have been reported. Most of these infections affected a previously damaged lung. Other infection sites included the skin, lymph nodes, and bursae. Five cases of disseminated infection have been reported. The antituberculous drugs associated with the most favorable susceptibility patterns are rifampin and ethambutol. Because of the slow growth of M. malmoense on conventional, egg-based bacteriologic media, the incubation time should be >6 weeks; special solid and liquid media are recommended. We report a case of disseminated pulmonary and gastrointestinal infection due to M. malmoense in a patient with AIDS, who was treated successfully with a combination of rifabutin (ansamycin), clofazimine, and isoniazid. In addition, we review the characteristics of extrapulmonary and disseminated infections due to M. malmoens

Nontoxigenic Corynebacterium diphtheriae Isolated from Intravenous Drug Users

During a prospective study 117 intravenous drug users were screened for infection with Corynebacterium diphtheriae. Nontoxigenic C. diphtheriae was found in 5 of 132 throat swab specimens and in 5 of 28 skin ulcer specimens taken from July 1991 to April 1992. When phenotypic and molecular typing methods were used, these 10 strains were shown to belong to a single clone. During the same period no strain was isolated from 200 controls. Clinical manifestations of infection were not clearly attributable to C. diphtheriae—no typical membranous pharyngitis was present. The presence of a single clone among homeless intravenous drug users in Zurich indicates the presence of C. diphtheriae in parts of the population with poor standards of hygiene and low socioeconomic statu

Is depression a risk factor for heart complaints?: Longitudinal aspects in the Zurich study

Background: The objective of this longitudinal study was to assess the association between major depression and heart complaints in a population of young and healthy adults. Methods: Starting at the age 20/21, participants of the Zurich Study underwent 6 structured, psychological interviews during a span of 20years. We evaluated longitudinal data from 277 persons who participated in all 6 interviews including questions about heart complaints. Results: Over 20years, heart complaints were reported by two thirds of participants, and the frequency of depression was 11.4%. At the age of 40/41, heart complaints were significantly associated with earlier heart complaints and major depression, both more often in women. Recurrent brief depression showed a tendency, but neither minor depression nor depressive symptoms were predictive for later heart complaints. Conclusions: This study suggests that major depression is a predictor for heart complaints at the age of 40 and that the severity of depressive disorder in younger age has an effect on subsequent heart complaints. Follow-up data will help to elucidate whether these subjective heart complaints show any correlation with a later coronary heart diseas

Attenuated and Nonproductive Viral Transcription in the Lymphatic Tissue of HIV-1-Infected Patients Receiving Potent Antiretroviral Therapy

Human immunodeficiency virus type 1 (HIV-1) RNA that persists in the lymphoid tissue of patients despite treatment with highly active antiretroviral therapy (HAART) may represent extracellular virions or intracellular RNAs residing within HIV-infected cells. To further characterize residual viral transcription, tonsil biopsy specimens from patients receiving long-term HAART, untreated patients, and patients undergoing 2 weeks of structured treatment interruption were analyzed by polymerase chain reaction quantification of virion-encapsidated RNA, intracellular unspliced HIV RNA (HIV UsRNA), multiply spliced HIV RNA encoding tat and rev (HIV MsRNA), and HIV DNA. Tonsil biopsy specimens from viremic patients harbored high amounts of virions, which primarily stemmed from local production, as indicated by a strong correlation of extracellular tonsillar RNA with intracellular HIV-1 nucleic acid levels but not with plasma viremia, and as shown by phylogenetic analysis of clonal env sequences from lymphoid tissue and plasma. In patients receiving HAART, intracellular HIV UsRNA persisted at significantly decreased levels, whereas HIV MsRNA and lymphoid virion levels were depleted. Thus, residual lymphoid HIV-1 RNA in patients receiving HAART indicates attenuated viral transcription in HIV-1-infected cells that lack virion productio

Equal Amounts of Intracellular and Virion‐Enclosed Hepatitis C Virus RNA Are Associated with Peripheral‐Blood Mononuclear Cells In Vivo

Background. Hepatitis C virus (HCV) replicating in peripheral‐blood mononuclear cells (PBMCs) may represent an extrahepatic viral reservoir. Quantitation of HCV RNA with regard to its subcellular distribution and longitudinal course is needed for better understanding of the largely unexplored in vivo dynamics and potential pathogenetic significance of HCV in PBMCs. Methods. Plasma and PBMCs from 30 patients coinfected with HCV and human immunodeficiency virus were evaluated in cross‐sectional and longitudinal analyses, for up to 40 months. Differential extraction of virion‐enclosed HCV RNA associated with cells was performed in parallel with extraction of total cellular HCV RNA. HCV RNA of either orientation was quantified by real‐time polymerase chain reaction. Results. HCV RNA was detected only in PBMCs from patients with viremia and at relatively stable quantities over time. Intracellular HCV RNA corresponding to ∼60% of total cellular HCV RNA was strongly correlated with virion‐enclosed HCV RNA but was only weakly associated with viral loads in plasma. In contrast, the ratio of HCV RNA load in PBMCs versus that in plasma was patient specific and stable over time. Conclusions. The substantial and patient‐specific amounts of intracellular HCV RNA found by the present study support a concept of low‐level replication in PBMCs. There was no evidence for persistent HCV infection in PBMCs after clearance of viremia in plasm

Predictive Value of Bronchoalveolar Lavage in Excluding a Diagnosis of Pneumocystis carinii Pneumonia During Prophylaxis with Aerosolized Pentamidine

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidin

Phase II Study of Vicriviroc versus Efavirenz (both with Zidovudine/Lamivudine) in Treatment-Naive Subjects with HIV-1 Infection

Background. Vicriviroc (VCV) is a CCR5 antagonist with nanomolar activity against human immunodeficiency virus (HIV) replication in vitro and in vivo. We report the results of a phase II dose-finding study of VCV plus dual nucleoside reverse-transcriptase inhibitors (NRTIs) in the treatment-naive HIV-1-infected subjects. Methods. This study was a randomized, double-blind, placebo-controlled trial that began with a 14-day comparison of 3 dosages of VCV with placebo in treatment-naive subjects infected with CCR5-using HIV-1. After 14 days of monotherapy, lamivudine/zidovudine was added to the VCV arms; subjects receiving placebo were treated with efavirenz and lamivudine/zidovudine; the planned treatment duration was 48 weeks. Results. Ninety-two subjects enrolled. After 14 days of once-daily monotherapy, the mean viral loads decreased from baseline values by 0.07 log10 copies/mL in the placebo arm, 0.93 log10 copies/mL in theVCV25 mg arm, 1.18 log10 copies/mL in the VCV 50 mg arm, and 1.34 log10 copies/mL in the VCV 75 mg arm (P < .001 for each VCV arm vs. the placebo arm). The combination-therapy portion of the study was stopped because of increased rates of virologic failure in the VCV 25 mg/day arm (relative hazard [RH], 21.6; 95% confidence interval [CI], 2.8-168.9) and the VCV 50 mg/day arm (RH, 11.7; 95% CI, 1.5-92.9), compared with that in the control arm. Conclusion. VCV administered with dual NRTIs in treatment-naive subjects with HIV-1 infection had increased rates of virologic failure, compared with efavirenz plus dual NRTIs. No treatment-limiting toxicity was observed. Study of higher doses of VCV as part of combination therapy is warrante

Cytomegalovirus Retinitis: Decreased Risk of Bilaterality with Increased Use of Systemic Treatment

Cytomegalovirus (CMV) retinitis may be treated systemically or intravitreally. We reviewed retrospectively patients with CMV retinitis, in order to determine whether systemic treatment was associated with less spread of CMV retinitis from one eye to the other. Of 222 cases, 92 patients had bilateral disease at onset of CMV retinitis, leaving 130 for analysis. Bilaterality occurred in 10 patients during 12,687 days of systemic treatment and in 34 during 14,791 days without systemic treatment (odds ratio [OR] = 2.92; confidence interval [CI], 1.44-5.90). Patients who had received systemic treatment for <50% of the follow-up period had a greater risk of bilaterality (OR = 3.7; CI, 2.79-4.54) than did the more intensively treated patients. CD4 cell levels also contributed to increased risk, but multivariate analysis showed that CD4 cell counts and treatment intensity were independent risk factors. CMV retinitis was more likely to become bilateral in patients who received less intravenous therapy. Local treatment can complete but does not replace systemically administered therap