Risa M. Webb

Epidemiologic and Molecular Characterization of an Outbreak of Candida parapsilosis Bloodstream Infections in a Community Hospital

ABSTRACT Candida parapsilosis is an important cause of bloodstream infections in the health care setting. We investigated a large C. parapsilosis outbreak occurring in a community hospital and conducted a case-control study to determine the risk factors for infection. We identified 22 cases of bloodstream infection with C. parapsilosis: 15 confirmed and 7 possible. The factors associated with an increased risk of infection included hospitalization in the intensive care unit (adjusted odds ratio, 16.4; 95% confidence interval, 1.8 to 148.1) and receipt of total parenteral nutrition (adjusted odds ratio, 9.2; 95% confidence interval, 0.9 to 98.1). Samples for surveillance cultures were obtained from health care worker hands, central venous catheter insertion sites, and medical devices. Twenty-six percent of the health care workers surveyed demonstrated hand colonization with C. parapsilosis, and one hand isolate was highly related to all case-patient isolates by tests with the DNA probe Cp3-13. Outbreak strain isolates also demonstrated reduced susceptibilities to fluconazole and voriconazole. This largest known reported outbreak of C. parapsilosis bloodstream infections in adults resulted from an interplay of host, environment, and pathogen factors. Recommendations for control measures focused on improving hand hygiene compliance.

Acute Flaccid Paralysis and West Nile Virus Infection

Acute weakness associated with West Nile virus (WNV) infection has previously been attributed to a peripheral demyelinating process (Guillain-Barré syndrome); however, the exact etiology of this acute flaccid paralysis has not been systematically assessed. To thoroughly describe the clinical, laboratory, and electrodiagnostic features of this paralysis syndrome, we evaluated acute flaccid paralysis that developed in seven patients in the setting of acute WNV infection, consecutively identified in four hospitals in St. Tammany Parish and New Orleans, Louisiana, and Jackson, Mississippi. All patients had acute onset of asymmetric weakness and areflexia but no sensory abnormalities. Clinical and electrodiagnostic data suggested the involvement of spinal anterior horn cells, resulting in a poliomyelitis-like syndrome. In areas in which transmission is occurring, WNV infection should be considered in patients with acute flaccid paralysis. Recognition that such weakness may be of spinal origin may prevent inappropriate treatment and diagnostic testing.

Clinical spectrum of muscle weakness in human west nile virus infection

Poliomyelitis has recently been identified as a cause of muscle weakness in patients with West Nile virus (WNV) infection. However, the clinical spectrum of WNV‐associated weakness has not been described. We reviewed data on 13 patients with WNV infection. Patients with muscle weakness were classified into one of three distinct groups based on clinical features. Group 1 comprised five patients who developed acute flaccid paralysis, four with meningoencephalitis and one without fever or other signs of infection. Paralysis was asymmetric, and involved from one to four limbs in individual patients. Electrodiagnostic studies confirmed involvement of anterior horn cells or motor axons. Group 2 involved two patients without meningoencephalitis who developed severe but reversible muscle weakness that recovered completely within weeks. Muscle weakness involved both lower limbs in one patient and one upper limb in the other. Group 3 consisted of two patients who experienced subjective weakness and disabling fatigue, but had no objective muscle weakness on examination. In addition to the three distinct groups, two other patients developed exaggerated weakness in the distribution of preexisting lower motor neuron dysfunction. We conclude that the clinical spectrum of WNV‐associated muscle weakness ranges from acute flaccid paralysis, with or without fever or meningoencephalitis, to disabling fatigue. Also, preexisting dysfunction may predispose anterior horn cells to additional injury from WNV. Awareness of this spectrum will help to avoid erroneous diagnoses and inappropriate treatment. Muscle Nerve 28: 302–308, 2003

An Investigation of Genital Ulcers in Jackson, Mississippi, with Use of a Multiplex Polymerase Chain Reaction Assay: High Prevalence of Chancroid and Human Immunodeficiency Virus Infection

In 1994, an apparent outbreak of atypical genital ulcers was noted by clinicians at the sexually transmitted disease clinic in Jackson, Mississippi. Of 143 patients with ulcers tested with a multiplex polymerase chain reaction (PCR) assay, 56 (39%) were positive for Haemophilus ducreyi, 44 (31%) for herpes simplex virus, and 27 (19%) for Treponema pallidum; 12 (8%) were positive for > 1 organism. Of 136 patients tested for human immunodeficiency virus (HIV) by serology, 14 (10%) were HIV-seropositive, compared with none of 200 patients without ulcers (P < .001). HIV-1 DNA was detected by PCR in ulcers of 6 (50%) of 12 HIV-positive patients. Multivariate analysis indicated that men with chancroid were significantly more likely than male patients without ulcers to report sex with a crack cocaine user, exchange of money or drugs for sex, and multiple sex partners. The strong association between genital ulcers and HIV infection in this population highlights the urgency of preventing genital ulcers in the southern United States.

West Nile poliomyelitis.

gen, and alpha fetoprotein, were negative. The x-ray films of the chest and computed tomography scan of the thorax and abdomen were normal. The patient was treated with subcutaneous heparin and diclophenac, and fever and migratory thrombophlebitis subsided. Because the patient had been working with manure several days before his initial symptoms, Q fever serologic testing was requested. The antibody levels measured by complement fixation (CF) against phase II Coxiella burnetii antigen was 1:512. By indirect immunofluorescence, the titers of IgM and IgG against phase I and II were 1:64 and 1:512 and 1:256 and >2,048, respectively. Antibody titers against Mycoplasma, Chlamydia, Legionella, enterovirus, and influenza were negative. Recovery was uneventful and the patient was asymptomatic during a follow-up visit 3 weeks later. Antiphospholipid antibodies were negative. Three months after the acute phase of the infection, new titers of antibodies (CF) against C. burnetii were 1:128. Two years after the episode the patient was asymptomatic. This patient is unique in that he had acute Q fever with migratory thrombophlebitis. A diagnosis of Trousseau’s syndrome associated with an occult malignancy was considered on admission, but it was excluded soon. The recent history of exposure to manure was the key for the clinical diagnosis. Although specific anti-coxiella treatment was not given, the patient followed a self-limited course, and both clinical and laboratory abnormalities promptly subsided. Microscopic vasculitis and thrombosis are commonly found in patients with other rickettsial infections (5), but vascular phenomena must be considered an exceptional event in patients with Q fever. However, thrombophlebitis and pulmonary embolisms have been occasionally reported (6–8). These unusual manifestations have been associated with aPL during the course of acute Q fever (7,8). Antibodies to phospholipids have been found in 80% of patients in a large series of acute Q fever (9). None of the patients in the study showed thrombotic events or cardiac valve involvement in contrast to patients with lupus or primary aPL syndrome in whom clinical manifestations attributed to aPL developed (9). This observation could be explained by the fact that aPL found in patients with lupus and primary aPL syndrome are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation, which has been characterized as a β2-glycoprotein I (apolipoprotein H). This glycoprotein seems to inhibit the activation of the contact phase system of the intrinsic pathway of blood coagulation (10). On the other hand, apolipoprotein H is not necessary for the aPL activity observed in patients with Q fever and other infectious diseases (10). According to these studies, the observation of low titers of aPL in the serum of our patient during the acute phase of Q fever must be seen as a finding of uncertain importance not necessarily associated with migratory thrombophlebitis. In short, migratory thrombophlebitis (Trousseau’s syndrome) should be added to the evergrowing list of unusual manifestations of Q fever.

Staphylococcus aureus bloodstream infections among patients undergoing electroconvulsive therapy traced to breaks in infection control and possible extrinsic contamination by propofol

Infectious complications associated with electroconvulsive therapy (ECT) are extremely unusual.When five of nine patients undergoing ECT at one facility on June 20, 1996 developed Staphylococcus aureus blood-stream infection (BSI), an investigation was initiated. A retrospective cohort study, a procedure review, and observational and microbiologic studies were performed. A case was defined as any patient who had ECT at Facility A from June 1, 1995 through June 20, 1996 and developed S. aureus BSI <30 days after ECT. The post-ECT S. aureus BSI rate was significantly greater on the epidemic day than the pre-epidemic period, (i.e., June 1, 1995 through June 19, 1996) (5 of 9 vs 0 of 54 patients, P < 0.001). All patients during the study period received propofol before ECT. Case patients were more likely than noncase patients to have higher maximum temperature after ECT (median 103.9[degree sign]F vs 100.0[degree sign]F, P < 0.03) and a greater time from preparation of intravenous medications to infusion (median 2.1 vs 1.1 h, P = 0.01). All case-patient S. aureus isolates were indistinguishable by pulsed field gel electrophoresis. Our investigation suggests that the ECT-associated S. aureus BSIs were associated with infection control breaks, which possibly led to the extrinsic contamination of propofol. Prevention of propofol-associated infectious complications requires aseptic preparation and use immediately before infusion. (Anesth Analg 1997;85:420-5)

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection

Background Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Decline in tuberculosis with 19 years of universal directly observed therapy in a comprehensive statewide program.

The Mississippi State Department of Health tuberculosis program serves a rural southeastern US state of 2.9 million people in an area of 121,489 km(2) (46,907 square miles). Statewide, directly observed therapy (DOT) began in 1986. To evaluate the programs effectiveness, trends in Centers for Disease Prevention and Control program indicators for 1981-2005 were compared and found to be significant (P < 0.0001). Inclusion of rifampin and pyrazinamide in the regimens was reviewed. An annual decline in cases and case rates began in 1990, falling by 65% by 2005. Successful DOT is feasible over a large geographic area.The Mississippi State Department of Health tuberculosis program serves a rural southeastern US state of 2.9 million people in an area of 121 489 km2 (46 907 square miles). Statewide, directly observed therapy (DOT) began in 1986. To evaluate the programs effectiveness, trends in Centers for Disease Prevention and Control program indicators for 1981-2005 were compared and found to be significant (P < 0.0001). Inclusion of rifampin and pyrazinamide in the regimens was reviewed. An annual decline in cases and case rates began in 1990, falling by 65% by 2005. Successful DOT is feasible over a large geographic area.

Chemotherapy of Tuberculosis

The management of tuberculosis (TB) can be a challenging process that has implications both for the affected patient and public health. Effective anti-TB chemotherapy both cures and renders the patient noncontagious. Biological factors specific to M. tuberculosis necessitate the use of multiple drugs for prolonged durations to adequately eradicate infection. Recommended regimens address the complexities of eliminating organisms from diverse reservoirs while preventing the emergence of drug resistance. First-line anti-TB therapy for drug susceptible disease effectively cures almost all patients within 6-9 months. The loss of first-line agents, due to resistance or intolerance, necessitates lengthy treatment courses, frequently 12-18 months or longer. Due to the long treatment times and the implications of missed doses, directly-observed therapy (DOT) is considered the standard of care. Drugs used for the treatment of TB have serious potential toxicities that require close monitoring and prompt response. A strong public health infrastructure and robust social supports are important elements to assure successful treatment. These numerous factors compel public health entities to take a lead role in the management of TB, either through the direct management of TB treatment or by assuring the activities of partner organizations.

The effect of estrogen on luteinizing hormone-releasing hormone binding sites in hypothalamic membranes

The binding sites for [125I]LHRH were characterized in membranes from the hypthalamus and the effect of estrogen on the binding characteristics was studied in ovariectomized female rats. The radioligand, [125I]LHRH, was found to bind specifically to membranes from the hypothalamus at a maximal level, with an optimal temperature of 0 degrees C and a pH between 7 and 8. The binding was enhanced by NaCl at a concentration of 0.1-0.2 M. The specifically bound [125I]LHRH was only displaced by LHRH, but not by sodium iodide (NaI), bovine serum albumin and other hormones, such as thyrotropin-releasing hormone, bradykinin, oxytocin, prolactin, luteinizing hormone and growth hormone. The divalent metal ions, copper (Cu2+) and mercury (Hg2+), inhibited the specific binding of [125I]LHRH completely, whereas magnesium (Mg2+) and calcium (Ca2+) caused a decrease in binding. As revealed from Scatchard plot analysis, the binding sites for [125I]LHRH in the hypothalamus had a dissociation constant of 0.40 +/- 0.03 microM and the maximum number of binding sites was 98.55 +/- 4.34 pmol/mg protein. Treatment of female rates (ovariectomized for 3 weeks) with 4 micrograms of estradiol benzoate caused a statistically significant decrease in the maximal number of binding sites without any significant effect on the dissociation constant. However, the direct addition of estradiol hemisuccinate to the membrane preparations had no statistically significant effect on the specific binding of [125I]LHRH. The present study provides the evidence that estrogen decreases the density of binding sites for [125I]LHRH in the hypothalamus in vivo.