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Malaria acquired in endemic areas poses a substantial risk to travelers arriving in or returning to the United States. Timely diagnosis and recognition of severe illness are crucial; however, many U.S.-based clinicians lack familiarity with this disease. We conducted a retrospective review of 100 cases of malaria in adults seen at a single urban university hospital during 2000-2017. Descriptive and analytical statistics were calculated, including logistic regression modeling case severity. Most of the patients presented with Plasmodium falciparum (76%), most commonly after travel from sub-Saharan Africa (94%) . Prior malaria experience was common (50%), but adherence to a prophylactic regimen was exceedingly rare (4%). Twenty-one patients had severe malaria, including 10 with cerebral malaria. Severity was predicted by high parasitemia, bandemia, hypoglycemia, and hypotension at the time of presentation. In 24 patients, the initial treatment regimen was changed, usually because of the appearance of clinical deterioration or drug toxicity. One patient required intravenous artesunate. All patients survived, although one suffered fetal loss. Among 30 patients initially evaluated at other institutions, 43% had been treated for an alternative diagnosis. The most common reasons for transfer of patients to our hospital were inadequate facilities and lack of expertise with malaria. There needs to be increased awareness among U.S.-based travelers and clinicians regarding malaria as a potentially lethal condition, emphasizing the use of appropriate prophylaxis. Our simple model of disease severity could serve frontline physicians when deciding which patients should be admitted to the intensive care unit or transferred for higher level care. more...

Background: Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission., Methods: We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk., Results: Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5-4.1); age 18-34 years, 10.8 (95% CI, 9.7-12.0); transgender women, 9.9 (95% CI, 6.9-14.0); Hispanics, 9.2 (95% CI, 7.2-11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1-8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL., Conclusions: STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation. more...

Health care-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are a burden on the health care system. Clinical laboratories play a key role in reducing this burden, as the timely identification of MRSA colonization or infection facilitates infection control practices that are effective at limiting invasive MRSA infections. The Xpert MRSA NxG assay recently received FDA clearance for the direct detection of MRSA from nasal swabs. This multicenter study evaluated the clinical performance characteristics of the Xpert MRSA NxG assay with prospectively collected rayon nasal swabs ( n = 1,103) and flocked swab (ESwab) nasal specimens ( n = 846). Culture-based identification methods and antimicrobial susceptibility testing were used as the reference standards for comparison. According to the reference method, the positivity rates for MRSA in the population evaluated were 11.1% (122/1,103) for rayon swabs and 11.6% (98/846) for flocked swabs. The overall sensitivity and specificity of the rayon swabs were 91.0% (95% confidence interval [CI], 84.6 to 94.9%) and 96.9% (95% CI, 95.7 to 97.8%), respectively, across eight testing sites. The flocked swab specimens were 92.9% sensitive (95% CI, 86.0 to 96.5%) and 97.6% specific (95% CI, 96.2 to 98.5%) for MRSA detection across six testing sites. The sensitivity and specificity of the combined flocked and rayon swab data were 91.8% (95% CI, 87.4 to 94.8%) and 97.2% (95% CI, 96.3 to 97.9%), respectively. The positive predictive value (PPV) for rayon swabs was 78.7%, versus 83.5% for ESwabs. The negative predictive values (NPVs) for rayon swabs and ESwab specimens were 98.9% and 99.1%, respectively. In conclusion, the Xpert MRSA NxG assay is a sensitive and specific assay for the direct detection of MRSA from nasal swab specimens., (Copyright © 2017 American Society for Microbiology.) more...

Background: Drug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC., Methods: We analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309). Using logistic regression, we assessed associations between patient characteristics and transmitted resistance to any antiretroviral., Results: Prevalence of TDR was 20.5%, of ADR 40.5%, and of CDR 45.1% in the respective analysis groups. From 2004 to 2013, TDR prevalence decreased for nucleoside and nucleotide analogue reverse transcriptase inhibitors (15.0 to 5.5%; p = 0.0003) and increased for integrase strand transfer inhibitors (INSTIs) (0.0-1.4%; p = 0.04). In multivariable analysis, TDR was not associated with age, race/ethnicity, HIV risk group, or years from HIV diagnosis., Conclusions: In this urban cohort of HIV-infected persons, almost half of participants tested had evidence of CDR; and resistance to INSTIs was increasing. If this trend continues, inclusion of the integrase-encoding region in baseline genotype testing should be strongly considered. more...

Background and Aims: Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients., Methods and Results: Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/μl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/μl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/μl, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/μl, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/μl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R(2) = 0.2611, p < 0.05; R(2) = 0.2722, p < 0.05; and R(2) = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R(2) = 0.26, p = 0.026)., Conclusions: Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.) more...

Context: Use of reference laboratories for selected laboratory testing (send-out tests) represents a significant source of laboratory costs. As the use of more complex molecular analyses becomes common in the United States, strategies to reduce costs in the clinical laboratory must evolve in order to provide high-value, cost-effective medicine., Objective: To report a strategy that employs clinical pathology house staff and key hospital clinicians in the effective use of microbiologic send-out testing., Design: The George Washington University Hospital is a 370-bed academic hospital in Washington, DC. In 2012 all requisitions for microbiologic send-out tests were screened by the clinical pathology house staff prior to final dispensation. Tests with questionable utility were brought to the attention of ordering clinicians through the use of interdisciplinary rounds and direct face-to-face consultation., Results: Screening resulted in a cancellation rate of 38% of send-out tests, with proportional cost savings. Nucleic acid tests represented most of the tests screened and the largest percentage of cost saved through screening. Following consultation, requested send-out tests were most often canceled because of a lack of clinical indication., Conclusions: Direct face-to-face consultation with ordering physicians is an effective, interdisciplinary approach to managing the use of send-out testing in the microbiology laboratory. more...

Tumor necrosis factor alpha (TNF-α) inhibitors are widely used for the treatment of various inflammatory conditions. They are associated with an increased risk for infections. We report a case of herpes simplex virus type 1 (HSV-1) encephalitis in a patient receiving etanercept and review the literature on TNF-α and TNF-α inhibitors, and their importance in the pathophysiology of herpes simplex encephalitis. more...

Atrial-esophageal fistula is a rare but often fatal complication of catheter radiofrequency ablation. Patients occasionally have bacteremia and have been misdiagnosed with endocarditis. Infectious diseases specialists are often consulted and need to be aware of this complication. We report a case of atrial-esophageal fistula after radiofrequency ablation that illustrates the salient features of this illness. more...

Leptin, the protein product of the obese gene (ob), is secreted by adipocytes. Circulating leptin levels correlate with fat mass in humans, including individuals infected with HIV. Leptin serves as an adipostatic hormone, a permissive factor for reproduction and a modulator of immune function. Leptin is a cytokine, and has been demonstrated to enhance CD4 cell proliferation and IL-2 secretion from CD4 cells in vitro. The role of leptin in HIV-positive patients treated with highly active antiretroviral therapy (HAART) has not been well defined. We haveevaluated leptin levels in HIV-infected individualsduringthe early phase of HAART. We measured plasma leptin levels in 15 antiretroviral-naive HIV positive patients at baseline and after 1 and 4 weeks of HAART. After the first week of therapy, mean leptin level and CD4 count were increased compared to baseline, 6.0 vs 7.2 ng/ml (p = 0.004) and 377 vs 432 cells/ul (p = 0.014), respectively. In contrast, mean body mass index (BMI) remained unchanged 27.0 vs 26.8 kg/m2 (p < 0.08). After four weeks of therapy, leptin and BMI values were unchanged compared to baseline, 6.0 vs 5.9 (p < 0.4) and 27.0 vs 26.9 (p < 0.5), respectively, whereas CD4 count continued to increase to 491 cells/ul (p < 0.012 compared to baseline). These data demonstrate an early transient increase in plasma leptin levels in HIV positive patients initiated on HAART, despite a lack of change in BMI. It is unclear if the transient increase in leptin is related to its role as a cytokine, a metabolic regulator, or reproductive factor. more...

Background: A recent resurgence of primary and secondary syphilis has been observed in certain population groups, particularly among persons infected with human immunodeficiency virus (HIV). Liver involvement is an infrequently recognized complication of early syphilis, with no previous reports among HIV-infected patients., Methods: We describe 7 cases of syphilitic hepatitis in HIV-positive individuals and review the literature., Results: At our institutions, all patients presented with a rash consistent with secondary syphilis. Each case was characterized by a conspicuous increase in serum alkaline phosphatase level (mean level +/- standard deviation, 905 +/- 523.6 IU/L) and milder elevations in serum transaminase levels. The mean CD4+ absolute T cell count was 317 cells/mm3, and the median rapid plasma reagin (RPR) titer was 1 : 128. There was a significant correlation between higher CD4+ cell counts and the RPR titers (R=0.93; P=.002). Symptomatic resolution and biochemical improvement, particularly a significant decrease in serum alkaline phosphatase levels (P=.02), occurred following antibiotic therapy., Conclusions: Hepatic dysfunction is not uncommon in HIV-infected persons and is attributable to multiple causes. In the appropriate clinical setting, syphilitic hepatitis is an easily diagnosed and reversible etiology of liver dysfunction. The recognition of this entity will prevent unnecessary evaluation of abnormal liver enzyme levels in HIV-positive patients. more...

Purpose: To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks., Method: A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events., Results: At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients., Conclusion: COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated. more...

Plasma lipid and lipoprotein levels were measured at baseline and after 8 weeks of highly active antiretroviral therapy among patients receiving delavirdine with or without a protease inhibitor (PI). In patients receiving nucleoside reverse transcriptase inhibitors (NRTI) plus delavirdine, there was a statistically significant increase in cholesterol and HDL levels, whereas those receiving NRTI plus a PI had no significant change in their HDL levels. When delavirdine was combined with a PI, there was a more dramatic increase in both cholesterol and HDL concentrations. more...

Objective: To survey the evolution over the past decade of attitudes and practices of obstetricians in maternal-fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV)-infected pregnant women., Methods: Directors of all 65 approved maternal-fetal medicine training programs were sent questionnaires, responses to which were to reflect the consensus among members of their faculties. Programs were stratified based upon the number of HIV-infected pregnant patients cared for in the previous year., Results: Responses reflect experience with over 1000 infected pregnant women per year, nearly one-quarter with advanced disease. Combination antiretroviral therapy was prescribed by all respondents, universally in the 2nd and 3rd trimesters. A three-drug regimen (often containing a protease inhibitor) was used more often by those who treated at least 20 HIV-infected pregnant patients per year than by those programs seeing a lower number of patients (80 vs 59%). Despite the known and unknown risks of the use of antiretrovirals during pregnancy, only half of all responding programs report adverse events to the Antiretroviral Pregnancy Registry; reporting was more common among the institutions seeing a higher number of patients (61 vs 45%). Seventy-eight percent of higher volume programs enroll their patients in clinical studies, usually multicenter, versus 35% of lower volume programs., Conclusions: Care for HIV+ pregnant women has dramatically changed over the past decade. Antiretroviral therapy is now universally prescribed by physicians involved in maternal-fetal medicine training programs. Given limited experience with these agents in the setting of pregnancy, it is essential for maternal-fetal medicine practitioners to actively report on adverse events and participate in clinical trials. more...

Objective: Comparison of stavudine (d4T), didanosine (ddI) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients., Design: Randomized, open-label., Setting: Fourteen HIV Clinical Research Centers., Patients: Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts > or = 200 x 10(6)/l and plasma HIV-1 RNA levels > or = 10,000 copies/ml., Interventions: Stavudine 40 mg and ddI 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV., Main Outcome Measures: The proportion of patients with plasma HIV-1 RNA levels < 500 copies/ml and < or = 50 copies/ml and changes in CD4 cell counts were compared., Results: In an analysis of the primary endpoint, 61% of patients on d4T + ddI + IDV and 45% of patients on ZDV + 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 < 500 copies/ml [95% confidence interval (CI) for the difference between proportions, 1.7-30.3%; P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels < 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddI + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% CI, -1.4% to 25.7%; P = 0.068). At 48 weeks 41% and 35% were < or = 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P > 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 x 10(6)/l cells for the d4T arm and 106 x 10(6)/l cells for the ZDV arm (P= 0.001). The occurrence of serious adverse events was not significantly different between arms., Conclusion: The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment. more...

Alterations in lipid metabolism have been associated with the use of protease inhibitors. Sequential lipid analyses were performed on serum samples from human immunodeficiency virus-infected antiretroviral-naive patients who received indinavir in combination with two nucleoside reverse transcriptase inhibitors. Serum levels of cholesterol, triglycerides, high-density lipoproteins (HDLs), and low-density lipoproteins (LDLs) were measured at baseline and at periodic intervals. After 48 weeks of indinavir therapy, mean serum levels +/- SD rose as follows: cholesterol, from 167.2 +/- 36.0 to 206.3 +/- 32.4 mg/dL (P < .0005); triglycerides, from 110.4 +/- 47.5 to 158.4 +/- 72.5 mg/dL (P < .0101); and LDLs, from 106.6 +/- 35.1 to 136.1 +/- 31.6 mg/dL (P = .0029). There was no significant change in the serum HDL fraction. Mean serum lipoprotein (a) levels +/- SD rose from 6.5 +/- 1.4 to 9.6 +/- 2.0 mg/dL after 30 weeks (P = .0695). Potential mechanisms for the noted increases include alterations in serum lipoprotein lipase activity or changes in hepatic lipid metabolism. The clinical significance of these changes remains to be determined. more...

Objective: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients., Design: A randomized, open-labeled, comparative trial., Setting: Outpatient clinics., Patients: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection., Interventions: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks., Main Outcome Measure: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium., Results: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups., Conclusions: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit. more...

We compared the efficacy of a 400-mg once-weekly dosage versus a 200-mg daily dosage of fluconazole for the prevention of deep fungal infections in a multicenter, randomized, double-blind trial of 636 human immunodeficiency virus-infected patients to determine if a less intensive fluconazole regimen could prevent these serious but relatively infrequent complications of AIDS. In the intent-to-treat analysis, a deep fungal infection developed in 17 subjects (5.5%) randomly assigned to daily fluconazole treatment and in 24 (7.7%) given weekly fluconazole during 74 weeks of follow-up (risk difference, 2.2%; 95% confidence interval [CI], -1.7% to 6.1%). Thrush occurred twice as frequently in the weekly versus daily fluconazole recipients (hazard ratio, 0.59; 95% CI, 0.40-0.89), and in a subset of patients evaluated, fluconazole resistance was infrequent. Fluconazole administered once weekly is effective in reducing deep fungal infections in patients with AIDS, but this dosage is less effective than the 200-mg-daily dosage in preventing thrush. more...

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels. more...

Three human immunodeficiency virus-infected subjects with progressive cytomegalovirus (CMV) retinitis despite prolonged antiviral therapy had buffy coat CMV isolates that were resistant to both ganciclovir and foscarnet. Genetic analysis of the resistant isolates showed that each contained a well-known ganciclovir resistance mutation in the viral UL97 phosphotransferase sequence, as well as a mutation (Ala to Val at codon 809, V809) in conserved region III of the DNA polymerase (Pol) sequence. A segment of the Pol sequence from one of the clinical isolates was transferred to CMV laboratory strain AD169 by homologous recombination. The recombinant virus containing V809 showed 6.3-fold increased foscarnet resistance and 2.6-fold increased ganciclovir resistance. Occurrence of the V809 mutation in 3 unrelated cases suggests that it is a clinically significant viral genetic marker for foscarnet resistance and decreased susceptibility to ganciclovir. more...

A wide variety of infectious agents has been associated with acute pancreatitis. Strict diagnostic criteria were developed to assess with relationship between individual microorganisms and acute pancreatitis. Pathologic or radiologic evidence of pancreatitis associated with well-documented infection was noted with viruses (mumps, coxsackie, hepatitis B, cytomegalovirus, varicella-zoster virus, herpes simplex virus), bacteria (Mycoplasma, Legionella, Leptospira, Salmonella), fungi (Aspergillus), and parasites (Toxoplasma, Cryptosporidium, Ascaris). Clues to the infectious nature of pancreatitis lay in the characteristic signs and symptoms associated with the particular infectious agent. How often these agents are responsible for idiopathic pancreatitis is unclear. more...

Background: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing., Methods: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex., Results: In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P = 0.03). Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin. Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P=0.03). Survival was similar in all three groups., Conclusions: For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated. more...

In a retrospective review of microbiology records at the George Washington University Hospital from 1980 through 1990, Mycobacterium kansasii bacteremia was identified in 10 patients; this finding represented 4.5% of nontuberculous mycobacterial blood cultures. M. kansasii was isolated from respiratory specimens from all 10 patients, and pulmonary parenchymal changes were noted in five patients. The median survival time was 14 weeks; however, only five patients received therapy with two or more drugs active against M. kansasii. more...

Background: Anterior segment findings in AIDS patients presenting with cytomegalovirus (CMV) retinitis have not been specifically addressed in the American literature., Methods: Our study evaluated 21 AIDS patients with CMV retinitis., Results: Nineteen (90%) of these patients exhibited corneal endothelial deposits concurrent with CMV retinitis. The endothelial deposits were microscopic, opaque, linear flecks arranged in a reticular-like fashion. Of 42 eyes evaluated, 32 (76%) demonstrated active CMV retinitis. Corneal endothelial deposits were noted in 26 (81%) of the 32 eyes with retinitis. These corneal endothelial deposits were absent in the eyes which did not have CMV retinitis., Conclusion: Meticulous examination of the retina of an HIV-positive or AIDS patient who presents with reticularly arranged, linear, flecked corneal endothelial deposits should be performed to ensure that the diagnosis of CMV retinitis can be ruled out. more...

Wasting syndrome is a common complication of HIV infection and is marked by progressive weight loss and weakness, often associated with fever and diarrhea. The pathophysiologic mechanisms responsible for this syndrome are not well defined, but it is clear that this is a multifactorial process in which the relative contribution of individual etiologic factors vary among patients. Considerations include inadequate diet, malabsorptive phenomena, metabolic derangements, and cytokine activity. The onset of opportunistic infections is often accompanied by a hypermetabolic state characterized by progressive weight loss. Potential cytokines that may promote weight loss in AIDS patients include tumor necrosis factor, interleukin-1, interleukin-6, and alpha-interferon. At present there is no effective treatment. Multiple therapeutic methods, including enteral and parenteral alimentation, appetite stimulants, recombinant growth hormone, and cytokine modulators, are currently being explored. more...

The CNS is an unusual site of ectopic infection in schistosomiasis. Cerebral lesions are caused primarily by Schistosoma japonicum, and spinal cord lesions are due primarily to Schistosoma mansoni and Schistosoma haematobium. S. haematobium is an unusual cause of cerebral mass lesions although schistosomal eggs can be frequently found in the brains of individuals in countries where S. haematobium is endemic. We describe a patient with a space-occupying cerebral lesion and schistosomal granulomas on pathological examination. S. haematobium was identified in urine and serologically. The cerebral lesion responded to therapy with praziquantel and corticosteroids. It has been postulated that granulomatous lesions develop following egg laying by errant worms migrating in the vicinity of the cerebral circulation or in response to eggs deposited from more distant sites by embolization. A species-specific serological diagnosis can be made by FAST (Falcon assay screening test)-ELISA with western blot confirmation. more...

Extrapulmonary pneumocystosis recently has been reported in a number of tissues. Most cases occurred in patients receiving aerosolized pentamidine prophylaxis. We report a case of disseminated pneumocystosis presenting as a large pleural effusion without apparent lung involvement where Pneumocystis carinii was the only pathogen identified. The absence of parenchymal lesions on chest x-ray film, the lack of hypoxemia and the minimal uptake of gallium all argue against significant lung involvement. The patient was successfully treated with chest tube drainage, intravenous and inhaled pentamidine and orally administered dapsone and trimethoprim. The addition of inhaled pentamidine to intravenously administered pentamidine may have increased pleural fluid levels substantially and its use coincided with the patient's improvement. more...

Objective: To determine attitudes and practices of obstetricians in maternal-fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV) infection and the use of zidovudine during pregnancy., Methods: We sent a questionnaire to the directors of all 78 approved maternal-fetal medicine fellowship programs. The responses, reflecting the consensus of the staffs of each program, were obtained and tabulated., Results: Although their programs annually provide care for more than 2100 pregnant women infected with HIV, less than 25% of all maternal-fetal medicine fellowship directors reported that their patients participate in multicenter studies of HIV infection complicating pregnancy. Nearly two-thirds of the infected women are excluded from such multicenter studies. More than 70% of all program directors believe that zidovudine should be offered to symptomatic pregnant women infected with HIV; one-half question whether zidovudine poses short-term fetal risks. Nevertheless, nearly half of all HIV-infected pregnant women they manage are excluded from trials of zidovudine therapy during pregnancy., Conclusions: Many HIV-infected pregnant women who receive care in clinics of maternal-fetal medicine fellowship programs are excluded from multicenter studies. Consideration should be given to creating a national registry for this important, currently unreported, clinical resource. more...

Sexually active travelers are at risk for a variety of STDs, including traditional venereal infections such as gonorrhea, chlamydial urethritis, syphilis, chancroid, and herpes simplex infection. More recently, hepatitis B, hepatitis C, and HIV-1 have also been described. Risk varies depending on the geographic area of travel and the type of sexual contact. Physicians should be aware of the prevalence of antimicrobial resistance of N. gonorrhoeae and H. ducreyi because this will affect empiric antibiotic therapy. Prevention should focus on proper and consistent usage of barrier contraceptives. more...

Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured in 22 AIDS patients who had detectable serum antigen at baseline after induction and maintenance therapy of foscarnet for cytomegalovirus retinitis in phase I/II multicenter trials. The HIV p24 antigen levels decreased from a baseline value of 199 +/- 236 (mean +/- SD) and 140 pg/mL (median) to 106 +/- 218 and 28 pg/mL after 14 days of foscarnet induction therapy (60 mg/kg every 8 h). During chronic foscarnet maintenance, there was a sustained decrease in mean HIV p24 antigen levels below pre-foscarnet therapy baseline concentrations for a median of 16 weeks after foscarnet induction. These results provide evidence for a sustained clinical antiretroviral effect of chronic foscarnet maintenance therapy, consistent with a recent report that foscarnet-treated AIDS patients live longer than ganciclovir-treated patients. more...

Note from Dr. Merle A. Sande--The role of Mycobacterium avium as a pathogen in the human immunodeficiency virus-infected population has been confusing and controversial to clinicians who care for AIDS patients. The organism is commonly isolated from respiratory secretions of patients with other infections and often seems part of the resident flora; even when isolated from the bone marrow or bloodstream, its impact on the course of AIDS and contribution to systemic diseases are unknown. However, an increasing subset of patients without other documented opportunistic infections or malignancies has symptoms that respond to therapy directed against M. avium. Studies are in progress to evaluate chemotherapeutic agents. Accordingly, the subject is here reviewed and guidelines offered to infectious disease clinicians by one with a long-standing interest in mycobacterial disease who has made numerous contributions to the field. more...

Two cases of invasive aspergillosis in AIDS patients are reported and previously reported AIDS-related cases are reviewed. Only one-half of all cases were diagnosed antemortem. Outcome is poor despite antifungal and surgical therapy. Normal phagocytic function is important in host defense against Aspergillus species. HIV-infected patients may have impaired phagocytic function as a result of antiretroviral therapy or treatment of opportunistic infection, or due to HIV infection itself. As the lifespans of HIV-infected patients are extended by antiretroviral therapy, an increasing awareness of Aspergillus infection as an opportunistic pathogen will be necessary. more...

We evaluated the clinical, immunologic, and virologic effects of oral treatment with ribavirin and isoprinosine for up to 3 months in asymptomatic, HIV-culture-positive homosexual men. Fifteen consecutive men received isoprinosine 4 g/day (1 g q.i.d.), and 800 (9 men) or 1,200 mg/day (6 men) of ribavirin. Five men in each ribavirin dosage group completed at least 2 months of treatment. No unexpected toxicities were observed. Eight minor HIV-related events occurred in six men while on study. All men remained HIV-positive, and time to positive culture decreased by at least 4 days in three men from each treatment group. Serum p24 levels did not change in two men who were p24 antigenemic and received 800 mg/day of ribavirin. Treatment was associated with a generalized lymphopenia affecting all lymphocyte subsets including CD4, which was partially reversible 1 month after stopping treatment. Most of the men remained anergic on DTHS skin testing. No improvements were noted in in vitro lymphoproliferative responses to antigens or in NK cell activity (which decreased significantly in the 1,200 mg/day ribavirin group). Although well tolerated at the doses employed, the combination of ribavirin and isoprinosine produced an unexpected generalized lymphopenia and did not exhibit HIV-suppressive or immunorestorative effects. more...

The health status of 239 Ethiopian refugees in the United States was evaluated. Over 70 per cent were males 15-30 years old. Positive PPDs (purified protein derivative of tuberculin) were observed in 72 per cent and 3.4 per cent had abnormal chest x-rays. One patient had active tuberculosis. Other laboratory abnormalities included: intestinal parasites (36.7 per cent), anemia (14.9 per cent), eosinophilia (14 per cent), positive syphilis serology (7.5 per cent), and hepatitis B surface antigenemia (9.4 per cent). The most prevalent intestinal parasites were Giardia lamblia, Trichuris trichiura, and Schistosoma mansoni. more...

The in vitro effects of thymosin fraction 5 (TF5) and lithium chloride (LiCl) on the ability of peripheral blood mononuclear cells (PBMC) obtained from 37 normal male donors and 33 male patients with AIDS-related complex (ARC) to respond to alloantigenic stimulation (mixed leukocyte reaction, MLR) and to produce interleukin 2 (IL-2) in response to mitogens were studied. TF5 significantly increased MLR responses in normal donors (P less than 0.01) and in a group of 33 ARC patients with depressed cellular immunity (P less than 0.05). Similar effects were observed when LiCl was added to the MLR assays in both the normal and the ARC patient groups. Furthermore, TF5 and LiCl exhibited additive immunoenhancing properties. In 10 normal donors TF5 enhanced phytohemaggutinin (PHA)-induced IL-2 production as well as IL-2 production in response to pokeweed mitogen (PWM) (P less than 0.02). TF5-mediated enhancement of IL-2 production by PBMC obtained from ARC patients was observed in response to both mitogens, i.e., PHA and PWM. Additionally, LiCl increased PHA-induced IL-2 production in both normal subjects and ARC patients. LiCl and TF5 together had an additive effect in the enhancement of IL-2 production in both groups of subjects. Our data extend previous observations regarding the immunoregulatory activities of TF5 and LiCl and provide evidence that PBMC obtained from ARC patients have the potential to respond in vitro to these agents. The significance of these findings is discussed. more...

Retrospective review of isolates of Capnocytophaga, a genus of capnophilic gram-negative bacilli, referred to the Massachusetts State Laboratory Institute in Boston revealed 31 patients with infection due to Capnocytophaga, 16 in nonimmunocompromised hosts. These infections included empyema (three patients), lung abscess (one), sinusitis (one), conjunctivitis (three), subphrenic abscess (one), wound (three), osteomyelitis (one), and bacteremia (three). Two of the wound infections were closed-fist injuries involving bone or soft tissue. Capnocytophaga was frequently isolated as part of a polymicrobial infection with other oral flora. There was only one death in the nonimmunocompromised group. In contrast, of 15 immunocompromised patients with 16 episodes of bacteremia due to Capnocytophaga, 87% had leukopenia and 73% had significant oral pathology such as gingivitis, mucositis, or ulceration. Five immunocompromised patients died. Thus, Capnocytophaga species may cause disease in both nonimmunocompromised and immunocompromised hosts. Isolation of this organism should suggest an oral source for infection. more...

An antibodylike paraprotein has been isolated from a patient with multiple myeloma and autoimmune hyperlipoproteinemia. The paraprotein bound to apolipoprotein B (apo B)-containing lipoproteins that formed macromolecular aggregates, and globules thought to be aggregated complexes of lipoproteins and reactive immunoglobulins were observed circulating within the retinal blood vessels of this patient. This binding specificity permitted purification of the paraprotein from both the agglutinated immune complexes and from the plasma. The protein is an IgA, kappa-immunoglobulin which exists primarily in a polymeric state. Capillary immunoprecipitation demonstrated reactivity with very low density lipoproteins (VLDL) and low density proteins (LDL), but not with high density lipoproteins (HDL). Delipidated apo B and apo E, but not apo A or apo C, formed precipitates with this immunoglobulin. In using a radioimmunoassay format, the affinity of the immunoglobulin was greatest for VLDL and decreases sequentially for intermediate density lipoproteins and LDL. No binding occurred with a dispersion of LDL lipids or with HDL. Deglycosylation did not change the binding to LDL. The apolipoproteins B and E bound with similar affinity, but no binding occurred with apo A-I or apo A-II. Weak binding appeared to occur with apo C. This paraprotein immunoprecipitated apo B-containing lipoproteins from all classes of vertebrates tested. Displacement of the lipids of LDL by Triton X-100 resulted in the formation of an apo B-Triton complex which, however, did not bind to the immunoglobulin; apparently the binding site on apo B was lost. Upon enzymatic digestion with the IgA-specific protease from Streptococcus sanguis the immunoglobulin was cleaved into Fc and Fab fragments, and the binding of LDL occurred only with the latter, consistent with the behavior of an immunoglobulin. The immunoreactivity of this paraprotein with apo B and apo E raises the interesting possibility that it may be binding to a site on these apolipoproteins which is reactive with the apo B, E receptor of the plasma membrane, a site which is conserved throughout the vertebrate phylum. more...

Ten homosexual men received oral lithium carbonate at doses that maintained their serum lithium concentrations between 0.5 and 1.5 mEq/L. Prior to treatment all patients had HIV isolated from PHA-activated peripheral blood lymphocytes (PBLs) using a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA) assay for detection, and had an absolute number of CD4 (helper) lymphocytes of less than 300/mm3. Eight of 10 patients developed symptoms of drug toxicity requiring discontinuation of the drug in 7 patients. Two patients completed only 4-5 weeks of lithium therapy, and 5 patients received 7-8 weeks. All patients remained culture positive for HIV during the trial, and viral titers as measured by the antigen capture assay were unchanged or increased. There were no significant changes in the absolute number of CD4 lymphocytes, CD4/CD8 ratio, or phytohemagglutinin (PHA) or tetanus toxoid induced proliferative responses. There was a significant decrease in mixed lymphocyte reaction (MLR). Lithium carbonate demonstrated no immunorestorative or antiviral activity when given in therapeutic doses. Drug toxicity limited therapy in the majority of patients. more...

Thirty-six incoming house officers and 20 incoming third-year medical students had conjunctival cultures taken before and after hospital exposure. The groups were divided evenly between contact-lens and noncontact-lens wearers. A decrease in incidence of positive conjunctival cultures was observed after hospital exposure. Within this group, a lower incidence of positive cultures was observed in contact-lens wearers compared with noncontact-lens wearers. The clinical records of corneal ulcer patients during a three-year period from October 1982 through October 1985 were also reviewed. Significant associated risk factors were identified, the largest of which was contact-lens wear. more...

Forty-two male homosexuals and/or hemophiliacs with depressed helper/suppressor T-cell ratios were treated with one of three different doses of thymosin fraction 5 (TF5, 30, 60, and 120 mg), or a single dose of thymosin Alpha One (TA1, 600 micrograms), by daily subcutaneous (SQ) administration for 10 weeks, followed twice weekly for 4 weeks. No major toxicity was noted for any of the preparations tested, although three subjects treated with TF5 had to discontinue therapy because of severe local skin reactions. Of the doses and preparations tested, only 60 mg TF5 was capable of significantly improving (p less than 0.02) mean T-cell lymphoproliferative responses to alloantigens (MLR) for six HTLV-III seropositive subjects who were abnormal prior to therapy. Peripheral blood lymphocytes from subjects treated with 60 mg TF5 also exhibited a transient restoration of mean mitogen-induced interleukin-2 (IL-2) production to normal. No effects were observed with any of the four treatment regimens on absolute helper T-cell numbers, NK activity, antibody titers to HTLV-III, or in the expression of a variety of surrogate markers for acquired immunodeficiency syndrome (AIDS). Four of the six seropositive subjects treated with 60 mg TF5 exhibited a return to depressed baseline MLR, after switching to twice weekly injections. With a median follow-up time of 20 months, six cases of AIDS developed. However, none of the five subjects whose MLR improved following treatment progressed to AIDS. We recommend daily subcutaneous (SQ) administration of 60 mg (40 mg/m2) TF5 for use in combined modality trials, along with drugs capable of suppressing replication of HTLV-III. more...

10 patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or lymphadenopathy syndrome (LAS) were given 200-250 mg ampligen, a mismatched double-stranded (ds) RNA with in-vitro antiviral activity against human immunodeficiency virus (HIV), twice a week for up to 18 weeks, without side-effects or toxicity. In all 9 patients who were positive for HIV RNA in peripheral blood mononuclear cells before therapy, levels became undetectable between days 10 and 40 of the start of therapy. 6 of the 7 patients with ARC or LAS also showed a progressive reduction in HIV load as measured by co-culture assays. All 10 patients had augmentation of delayed-type hypersensitivity skin reactions. Other changes noted during ampligen therapy included an increase in or maintenance of numbers of helper-inducer T lymphocytes, improvements in HIV-related symptoms, rises in titre of neutralising antibodies against HIV, and restoration of proper functioning of the natural lymphocyte antiviral dsRNA-dependent (2'-5'-oligoadenylate/RNA-ase L) pathway. Thus, in the short term, ampligen seems to have the dual ability to restore immunological function and to control HIV replication. more...

13 asymptomatic, HTLV-III/LAV-infected male homosexuals with generalized lymphadenopathy were treated with oral D-penicillamine. All patients had depressed T4/T8 ratios and 12 had impaired T-cell function. An escalating dose schedule was employed over 2-6 weeks with doses from 0.5 to 2 g/day. Generalized skin rashes developed in 4 patients which required discontinuation of therapy in one patient. Two patients developed mild transient elevations of hepatocellular enzymes. Reversible decreases in lymph node size, absolute lymphocyte counts, and T-cell lymphoproliferative responses were observed in the majority of patients without change in baseline T4/T8 ratios. All 10 patients treated for at least 2 weeks exhibited evidence for suppression of HTLV-III/LAV replication; complete inhibition of virus expression was seen in 60% of patients treated for 6 weeks. Three of the patients treated for 6 weeks remained culture negative for at least 6 weeks after stopping the drug. D-Penicillamine appears to be an effective drug for suppressing HTLV-III/LAV expression in vivo. Its potential role in the treatment of patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) will require further evaluation. more...

A 37-year-old homosexual man was evaluated for a one-week history of hematochezia. Results of a physical examination were remarkable only for grossly bloody stool. Sigmoidoscopy to 30 cm showed a friable mucosa compatible with an acute colitis, and a rectal biopsy specimen demonstrated an increased plasma cell infiltrate. Stool cultures subsequently yielded Aeromonas hydrophila; serum human T-cell lymphotropic virus type III antibody titer was positive. The patient responded to a course of treatment with sulfamethoxazole and trimethoprim with resolution of his symptoms and restoration of the bowel to a normal sigmoidoscopic appearance. Aeromonas hydrophila infection should be considered in the differential diagnosis of acute proctocolitis, particularly in patients with underlying immunodeficiency states. more...

A case of paranasal sinus mucormycosis in an immunocompetent patient is reported. After an extensive evaluation, no evidence of either diabetes mellitus or underlying immunologic abnormality was found. The combination of excisional surgery and amphotericin B therapy resulted in an excellent response. High-resolution axial and coronal computed tomography was useful in both planning treatment and monitoring the response to therapy. more...

Sonicated preparations of Giardia lamblia hydrolyze a variety of protein substrates including human immunoglobulin. Activity is increased by thiol-activating agents and inhibited by thiol proteinase inhibitors. About 55% of activity remains in the soluble fraction after high-speed centrifugation, and pretreatment with a nonionic detergent results in increased soluble activity. This suggests that the enzyme is membrane bound or associated with subcellular particles. Activity elutes as a major peak at 38,000 molecular weight by calibrated sieve chromatography. The favored sites of enzymatic cleavage of IgA1 are between the CH2 and CH3 domain and near the hinge region of the heavy chain. Similar cleavage patterns were identified using sonicated preparations of Entamoeba histolytica and Trichomonas vaginalis. more...