Marion L. Woods

Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease.

OBJECTIVES The objectives of this study were to test prospectively for an association between Chlamydia and atherosclerosis by comparing the incidence of the pathogen found within atherosclerotic plaques in patients undergoing directional coronary atherectomy with a variety of control specimens and comparing the clinical features between the groups. BACKGROUND Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue, but this association has not yet been regarded as established. METHODS Coronary specimens from 90 symptomatic patients undergoing coronary atherectomy were tested for the presence of Chlamydia species using direct immunofluorescence. Control specimens from 24 subjects without atherosclerosis (12 normal coronary specimens and 12 coronary specimens from cardiac transplant recipients with subsequent transplant-induced coronary disease) were also examined. RESULTS Coronary atherectomy specimens were definitely positive in 66 (73%) and equivocally positive in 5 (6%), resulting in 79% of specimens showing evidence for the presence of Chlamydia species within the atherosclerotic tissue. In contrast, only 1 (4%) of 24 nonatherosclerotic coronary specimens showed any evidence of Chlamydia. The statistical significance of this difference is a p value < 0.001. Transmission electron microscopy was used to confirm the presence of appropriate organisms in three of five positive specimens. No clinical factors except the presence of a primary nonrestenotic lesion (odds ratio 3.0, p = 0.057) predicted the presence of Chlamydia. CONCLUSIONS This high incidence of Chlamydia only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis that should be further studied.

DHEAS as an Effective Vaccine Adjuvant in Elderly Humans: Proof-of-Principle Studies

We have demonstrated that in aged mice, the titer of serum antibody induced against tetanus toxoid correlates with resistance to local paralysis caused by injection of tetanus toxin. Only mice immunized shortly after oral dosing with DHEAS demonstrated high serum antibody titers and complete protection from paralysis. These results became the basis for initiating proof-of-principle studies in human volunteers above age 65 using a licensed influenza vaccine and tetanus toxoid in two independent studies. The use of an oral delivery form of DHEAS before influenza vaccination was associated with a demonstrable increase in the number of individuals with a fourfold increase in HAI titers following vaccination. The overall mean increase in HAI titers was highest in the DHEAS-treated group. The use of DHEAS in the immunization of elderly subjects against tetanus toxoid, while unable to enhance the responses, was not a detriment to antibody response. We conclude that further studies will justify the use of DHEAS as an adjuvant for antigens that represent primary responses in the elderly.

Necrotizing group a streptococcal infections associated with streptococcal toxic shock syndrome

BACKGROUND Group A streptococci (GAS) cause a variety of life-threatening infectious complications, including necrotizing fasciitis (NF), purpura fulminans (PF), and streptococcal toxic shock syndrome (strepTSS), in which bacteremia is associated with shock and organ failure. METHODS We reviewed our experience in the management of patients with necrotizing GAS infections from 1991 to 1995. RESULTS Eight adult patients (6 NF, 2 PF) were identified. Patients presented with fever, leukocytosis, and severe pain, and rapidly developed shock and organ dysfunction. The diagnosis of strepTSS was confirmed in 6 cases. A total of 54 surgical procedures were required, including widespread debridements and amputations. Two patients died (25%). CONCLUSIONS Recognition of the need for aggressive diagnosis and surgical treatment of this most rapidly progressive surgical infection is necessary for successful management.

Artesunate is Ineffective in Controlling Valganciclovir-Resistant Cytomegalovirus Infection

To the Editor—Cytomegalovirus (CMV) disease is a common pathogen and represents a difficult clinical problem in transplant recipients. CMV-naive patients receiving a CMV-positive allograft may experience complications, such as retinitis, gastritis, colitis, and pneumonitis, which may force clinicians to reduce immunosuppressive agents, thereby risking rejection. However oral agents, such as valganciclovir, are effective in controlling such disease. Unfortunately, CMV resistance to oral valganciclovir is an emerging problem and poses particular management difficulties in renal transplant recipients, because alternative agents, such as foscarnet and cidofovir, are renal toxic [1]. Recently, the antimalarial agent arteseunate was reported as an effective agent against both wild-type and ganciclovir-resistant CMV [2]. Unlike ganciclovir, cidofovir, and foscarnet, artesunate is not nephrotoxic and is believed to inhibit viral replication via an alternate mechanism of action to DNA polymerase. We recently trialled artesunate in a renal transplant recipient with documented valganciclovir resistance mutations in CMV (suscepitible to cidofovir and foscarnet). Our CMV-naive, 47year-old female patient received a CMVpositive renal allograft 12 years previously and presented with a relapse of CMV colitis, with a high CMV load. She experienced 1 previous episode of CMV colitis documented with positive histopathology 2 years prior. Her medications at admission included oral valganciclovir (450 mg twice daily), diltiazem CD (240 mg twice daily), mycophenolate (1 g twice daily), prednisolone (10 mg daily), fenofibrate (48 mg daily), trandolapril (8 mg twice daily), pravastatin (80 mg daily), sertraline (50 mg twice daily), and esomeprazole (40 mg daily). Initial CMV quantitative polymerase chain reaction at admission was .1.1 3 10 copies/mL, exceeding the laboratory CMV disease threshold of 5000 copies/ mL. Her estimated glomerular filtration rate (modification of diet in renal disease formula) was 27 mL/min, thus limiting use of standard CMV antiviral agents. Initial therapy with CMV immunoglobulin and intravenous ganciclovir therapy failed to improve viral load. Immunosuppression was modulated by substituting mycophenolate with everolimus (.75 mg twice daily), and prednisolone therapy (10 mg daily) was continued. Intravenous artesunate (180 mg daily) was commenced, and the dosage was increased to 240 mg daily on day 7. A total of 20 days of intravenous artesunate therapy failed to significantly reduce CMV load on serial quantitative polymerase chain reaction assay. Subsequent therapy with foscarnet rapidly suppressed CMV load to undetectable levels. We found that artesunate was ineffective against this valganciclovir-resistant CMV strain. Alternate nonrenal toxic agents are needed for the treatment of these cases.

Extrinsic factors that put patients at risk of acquiring central nervous system infections

Although many host defenses, including physical barriers, phagocytic cells, and humoral elements, normally protect the central nervous system from microbial pathogens, a variety of extrinsic factors may compromise these defenses and put patients at risk of acquiring central nervous system infection. These risk factors include: (1) communication of the cerebrospinal fluid space with integumentary surfaces; (2) communication of the cerebrospinal fluid space with other body spaces through shunts; (3) suppurative foci contiguous to the central nervous system; (4) hematogenous spread of infectious agents; (5) new acquisition of infectious agents with a propensity for causing central nervous system infection; and (6) administration of certain antimicrobial or immunosuppressive drugs. Recognition that these factors are present and therefore that the patient is at risk allows monitoring for and prompt response to signs and symptoms of central nervous system infection.