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Menstrual toxic shock syndrome (TSS) emerged as a public health threat to women of reproductive age in 1979 80. We reviewed surveillance data for the period 1979 to 1996, when 5,296 cases were reported, and discuss changes in the epidemiologic features of TSS. [ABSTRACT FROM AUTHOR]

Synthesis of materials with desired structures, e.g., metal-organic frameworks (MOFs), involves optimization of highly complex chemical and reaction spaces due to multiple choices of chemical elements and reaction parameters/routes. Traditionally, realizing such an aim requires rapid screening of these nonlinear spaces by experimental conduction with human intuition, which is quite inefficient and may cause errors or bias. In this work, we report a platform that integrates a synthesis robot with the Bayesian optimization (BO) algorithm to accelerate the synthesis of MOFs. This robotic platform consists of a direct laser writing apparatus, precursor injecting and Joule-heating components. It can automate the MOFs synthesis upon fed reaction parameters that are recommended by the BO algorithm. Without any prior knowledge, this integrated platform continuously improves the crystallinity of ZIF-67, a demo MOF employed in this study, as the number of operation iterations increases. This work represents a methodology enabled by a data-driven synthesis robot, which achieves the goal of material synthesis with targeted structures, thus greatly shortening the reaction time and reducing energy consumption. It can be easily generalized to other material systems, thus paving a new route to the autonomous discovery of a variety of materials in a cost-effective way in the future.

Clearance of low-level viremia that persists in most HIV-1-positive individuals on antiretroviral therapy (ART) is an important milestone for efforts to cure HIV-1 infection. The level of persistent viremia on ART is generally below the lower limit of quantification (LOQ) of current FDA-cleared plasma HIV-1 RNA assays (20 to 40 copies/ml) but can be quantified by reverse transcriptase PCR (RT-PCR) assays with single-copy sensitivity. Such assays require multistep manual methods, and their low throughput limits the capacity to monitor the effects of interventions on persistent viremia. Recently, S. Bakkour, X. Deng, P. Bacchetti, E. Grebe, et al. (J Clin Microbiol 58:e01400-20, 2020, https://doi.org/10.1128/JCM.01400-20), reported the use of multiple replicates and Poisson statistics to infer HIV-1 RNA concentrations below the commercial LOQ of an automated platform (Hologic Panther Aptima). Here, we evaluate the detection and quantitation of low-level viremia using the following two adaptions of the automated platform: a multireplicate strategy (9×) and a concentrated single-replicate strategy in which 5 ml of plasma is concentrated by centrifugation (1×, concentrated). We compare these new methods to a recently reported manual integrase -targeting single-copy assay version 2 (iSCA v2). Using laboratory-generated HIV-1 RNA plasma samples at known concentrations, all three methods had similar sensitivity for HIV-1 RNA detection, although iSCA v2 was most sensitive (95% LOD, 2.3 copies/ml), 9× was marginally less sensitive (95% LOD, 3.0 copies/ml), and 1×, concentrated was least sensitive (95% LOD, 3.9 copies/ml). In contrast, for clinical plasma samples, 9× had greater sensitivity than iSCA v2 (82% of samples were quantifiable compared with 62% of samples by iSCA v2). These results support 9× as an acceptable high-throughput alternative to iSCA v2 for quantifying low-level viremia in individuals on ART., (Copyright © 2020 Jacobs et al.)

As a long-acting formulation of the nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV LA) has been proposed for use as preexposure prophylaxis (PrEP) and the prevalence of transmitted RPV-resistant viruses can be relatively high, we evaluated the efficacy of RPV LA to inhibit vaginal transmission of RPV-resistant HIV-1 in humanized mice. Vaginal challenges of wild-type (WT), Y181C, and Y181V HIV-1 were performed in mice left untreated or after RPV PrEP. Plasma viremia was measured for 7 to 10 weeks, and single-genome sequencing was performed on plasma HIV-1 RNA in mice infected during PrEP. RPV LA significantly prevented vaginal transmission of WT HIV-1 and Y181C HIV-1, which is 3-fold resistant to RPV. However, it did not prevent transmission of Y181V HIV-1, which has 30-fold RPV resistance in the viruses used for this study. RPV LA did delay WT HIV-1 dissemination in infected animals until genital and plasma RPV concentrations waned. Animals that became infected despite RPV LA PrEP did not acquire new RPV-resistant mutations above frequencies in untreated mice or untreated people living with HIV-1, and the mutations detected conferred low-level resistance. These data suggest that high, sustained concentrations of RPV were required to inhibit vaginal transmission of HIV-1 with little or no resistance to RPV but could not inhibit virus with high resistance. HIV-1 did not develop high-level or high-frequency RPV resistance in the majority of mice infected after RPV LA treatment. However, the impact of low-frequency RPV resistance on virologic outcome during subsequent antiretroviral therapy still is unclear. IMPORTANCE The antiretroviral drug rilpivirine was developed into a long-acting formulation (RPV LA) to improve adherence for preexposure prophylaxis (PrEP) to prevent HIV-1 transmission. A concern is that RPV LA will not inhibit transmission of drug-resistant HIV-1 and may select for drug-resistant virus. In female humanized mice, we found that RPV LA inhibited vaginal transmission of WT or 3-fold RPV-resistant HIV-1 but not virus with 30-fold RPV resistance. In animals that became infected despite RPV LA PrEP, WT HIV-1 dissemination was delayed until genital and plasma RPV concentrations waned. RPV resistance was detected at similar low frequencies in untreated and PrEP-treated mice that became infected. These results indicate the importance of maintaining RPV at a sustained threshold after virus exposure to prevent dissemination of HIV-1 after vaginal infection and low-frequency resistance mutations conferred low-level resistance, suggesting that RPV resistance is difficult to develop after HIV-1 infection during RPV LA PrEP., (Copyright © 2020 Melody et al.)

Strongylid nematodes in large terrestrial herbivores such as great apes, equids, elephants, and humans tend to occur in complex communities. However, identification of all species within strongylid communities using traditional methods based on coproscopy or single nematode amplification and sequencing is virtually impossible. High-throughput sequencing (HTS) technologies provide opportunities to generate large amounts of sequence data and enable analyses of samples containing a mixture of DNA from multiple species/genotypes. We designed and tested an HTS approach for strain-level identification of gastrointestinal strongylids using ITS-2 metabarcoding at the MiSeq Illumina platform in samples from two free-ranging non-human primate species inhabiting the same environment, but differing significantly in their host traits and ecology. Although we observed overlapping of particular haplotypes, overall the studied primate species differed in their strongylid nematode community composition. Using HTS, we revealed hidden diversity in the strongylid nematode communities in non-human primates, more than one haplotype was found in more than 90% of samples and coinfections of more than one putative species occurred in 80% of samples. In conclusion, the HTS approach on strongylid nematodes, preferably using fecal samples, represents a time and cost-efficient way of studying strongylid communities and provides a resolution superior to traditional approaches.

Background: Hand hygiene plays an important role in the prevention of Clostridium difficile (CD) infection (CDI). Patient hand hygiene (PHH) may be a potentially underused preventative measure for CDI. Patient mobility and acuity along with a lack of education present obstacles to PHH for the hospitalized patient. Surveys of patients at our institution showed a need for increased PHH opportunities. The objective of this study was to increase PHH and to examine if PHH affected CDI at our hospital., Methods: A biphasic, quasi-experimental study was performed to increase PHH through education for staff and to provide education, assistance, and opportunities to the patient for hand cleaning. PHH practice was assessed by patient surveys and analyzed by χ 2 test. PHH effect on CDI was determined by following health care facility-onset CD laboratory-identified events data analyzed by National Healthcare Safety Network standardized infection ratios (SIRs)., Results: PHH opportunities improved significantly (P < .0001) after staff and patient education. CD SIRs deceased significantly for 6 months (P ≤ .05) after the PHH intervention., Conclusions: PHH opportunities can be increased by providing education and opportunities for patients to clean their hands. PHH should be considered a relevant preventative measure for CDI in hospitalized patients., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Biodiversity conservation is one of the grand challenges facing society. Many people interested in biodiversity conservation have a background in wildlife biology. However, the diverse social, cultural, political, and historical factors that influence the lives of people and wildlife can be investigated fully only by incorporating social science methods, ideally within an interdisciplinary framework. Cultural hierarchies of knowledge and the hegemony of the natural sciences create a barrier to interdisciplinary understandings. Here, we review three different projects that confront this difficulty, integrating biological and ethnographic methods to study conservation problems. The first project involved wildlife foraging on crops around a newly established national park in Gabon. Biological methods revealed the extent of crop loss, the species responsible, and an effect of field isolation, while ethnography revealed institutional and social vulnerability to foraging wildlife. The second project concerned great ape tourism in the Central African Republic. Biological methods revealed that gorilla tourism poses risks to gorillas, while ethnography revealed why people seek close proximity to gorillas. The third project focused on humans and other primates living alongside one another in Morocco. Incorporating shepherds in the coproduction of ecological knowledge about primates built trust and altered attitudes to the primates. These three case studies demonstrate how the integration of biological and social methods can help us to understand the sustainability of human-wildlife interactions, and thus promote coexistence. In each case, an integrated biosocial approach incorporating ethnographic data produced results that would not otherwise have come to light. Research that transcends conventional academic boundaries requires the openness and flexibility to move beyond one's comfort zone to understand and acknowledge the legitimacy of "other" kinds of knowledge. It is challenging but crucial if we are to address conservation problems effectively.

Background: Peripherally inserted central catheters (PICCs) are a commonly used central intravenous (IV) access device, which can be associated with significant complications. Midline catheters (MCs) are peripheral IV access devices that may reduce the need for central lines and hence decrease central line-associated bloodstream infections. The objective of this study is to compare the utilization and safety of PICCs and MCs., Methods: This was a retrospective study comparing the use and outcomes of PICCs and MCs at a large academic medical center between January and May 2015. Data were collected using electronic medical records and IV team insertion data. Statistical software was used for analysis., Results: A total of 206 PICCs and 200 MCs were inserted in 367 patients within the study duration. Patients with MCs were more likely to have complications than those with PICCs (19.5% vs 5.8%, P < .0001)., Conclusions: MCs were associated with a higher risk of non-life-threatening complications versus PICCs, which showed fewer but more serious complications, including bacteremia. The decision to move toward more use of MCs is not without risk. Institutions should continue to review the utilization and safety data of IV catheter use to determine the most appropriate use of these devices., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Infection is one of the most serious complications following surgical placement of cardiac implantable electronic devices (CIEDs). Infection prevention efforts are necessary in reducing CIED infectious outcomes. These devices, however, are commonly inserted in higher risk patients, which may explain the ongoing risk of surgical site infection (SSI) in this population. The rates of CIED infection and utilization vary widely in the literature. The definitions of infection may also vary between clinical definitions and the National Healthcare Safety Network (NHSN) criteria., Methods: The primary objective of this study was to review patient data to identify risk factors for infection and readmission after CIED placement at an academic medical center. The secondary objectives were to compare the rates of SSI identified by NHSN criteria compared to that obtained by applying clinical infection definitions., Results: The overall rate of infection (SSI) was 1.9%, which was identical in both the clinical definition and NHSN reported data. The 30 day readmission rate and the 90 day readmission rate were 12.7% and 25.6% respectively with the most readmissions related to the patients' underlying medical conditions. A lower ejection fraction (EF) was identified as an independent risk factor for readmission, inpatient procedures, smoking and device infection were also significantly associated with readmission after CIED insertion., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Antimicrobial resistance is a worldwide concern of public health. Unfortunately, resistant bacteria are spreading to all ecosystems, including the strictly protected ones. We investigated antimicrobial resistance in gastrointestinal Enterobacteriaceae of wild mammals and people living within Dzangha-Sangha Protected Areas, Central African Republic, with an emphasis on extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance (PMQR) genes. We compare resistance genes found in microbiota of humans, gorillas habituated and unhabituated to humans and other wildlife. In gorillas, we additionally investigate the presence of ESBL resistant isolates after treatment by ceftiofur. We found a considerable prevalence of multiresistant Enterobacteriaceae isolates with ESBL and PMQR genes in humans (10% and 31%, respectively). Among wildlife the most significant findings were CTX-M-15-producing Klebsiella pneumoniae in a habituated gorilla and a multiresistant Escherichia coli isolate with gene qepA in an unhabituated gorilla. Other isolates from wildlife were mostly represented by qnrB-harboring Citrobacter spp. The relatedness of resistant E. coli was investigated in a PFGE-based dendrogram; isolates from gorillas showed less than 80% similarity to each other and less than 80% similarity to human isolates. No ESBL-producing isolates were found in animals treated by ceftiofur. Although we did not detect any bacterial clone common to wildlife and humans, we detected an intersection in the spectrum of resistance genes found in humans and gorillas, represented by blaCTX-M-15 and qepA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Enzymeimmunoassays (EIAs) allow researchers to monitor stress hormone output via measurement of fecal glucocorticoid metabolites (FGCMs) in many vertebrates. They can be powerful tools which allow the acquisition of otherwise unobtainable physiological information from both captive animals and wild animals in remote forest habitats, such as great apes. However, methods for hormone measurement, extraction and preservation need to be adapted and validated for field settings. In preparation for a field study of Western lowland gorillas (Gorilla gorilla gorilla) in the Central African Republic we used samples from captive gorillas collected around opportunistic stressful situations to test whether four different glucocorticoid EIAs reflected adrenocortical activity reliably and to establish the lag-time from the stressor to peak excretion. We also validated a field extraction technique and established a simple, non-freezer-reliant method to preserve FGCMs in extracts long-term. We determined the rate of FGCM change over 28 days when samples cannot be extracted immediately and over 12h when feces cannot be preserved immediately in alcohol. Finally, we used repeat samples from identified individuals to test for diurnal variation in FGCM output. Two group-specific assays measuring major cortisol metabolites detected the predicted FGCM response to the stressor reliably, whereas more specific cortisol and corticosterone assays were distinctly less responsive and thus less useful. We detected a lag time of 2-3 days from stressor to peak FGCM excretion. Our field extraction method performed as well as an established laboratory extraction method and FGCMs in dried extracts stored at ambient temperatures were as stable as those at -20 °C over 1 yr. Hormones in non-extracted feces in alcohol were stable up to 28 days at ambient temperatures. FGCMs in un-fixed gorilla feces deteriorated to almost 50% of the original values within 6h under field conditions. We detected no diurnal variation in FGCMs in samples from wild gorillas. Our study highlights the importance of thorough biological and immunological validation of FGCM assays, and presents validated, practical methods for the application of non-invasive adrenocortical monitoring techniques to field conservation contexts where it is crucially needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Inhaled amphotericin preparations have been used for prophylaxis against invasive aspergillosis in lung transplant recipients. However, no published data exist regarding the pharmacokinetic profile of amphotericin B lipid complex in lung transplant recipients., Methods: We prospectively determined the concentrations of amphotericin B in the epithelial lining fluid (ELF) and plasma after aerosolized nebulization (AeroEclipse), of amphotericin B lipid complex at 1 mg/kg every 24 hr for 4 days in 35 lung transplant recipients. One brochoalveolar lavage sample and a simultaneous blood sample were collected at various time points after the fourth dose from each subject. High-performance liquid chromatography and high-performance liquid chromatography-MS-MS were used to measure amphotericin B., Results: Concentrations of amphotericin B in ELF (median, 25-75 IQR) were at 4 hr (n=5) 7.20 μg/mL (1.3-17.6), 24 hr (n=6) 8.26 μg/mL (3.9-82.7), 48 hr (n=5) 2.15 μg/mL (1.4-5.5), 72 hr (n=4) 1.25 μg/mL (0.75-5.5), 96 hr (n=6) 0.86 μg/mL (0.55-1.4), 120 hr (n=4) 1.04 μg/mL (0.44-1.6), 144 hr (n=1), 4.25 μg/mL, 168 hr (n=3) 1.14 μg/mL, and 192 hr (n=1) 1 μg/mL. The plasma concentration of the drug remained below 0.08 μg/mL at all time points. During the study, the side effects noted included wheezing, coughing, and 12% decline in forced expiratory volume in 1 sec., Conclusions: We conclude that administration through aerosolized nebulization of amphotericin B lipid complex every 24 hr for 4 days in lung transplant recipients achieved amphotericin B concentrations in ELF above minimum inhibitory concentration of the Aspergillus nearly at 168 hr after the last inhaled dose and is well tolerated.

Background: Lung transplants, in particular, have the highest rate of infections among solid organ transplant recipients. However, there is no existing objective measure to predict the development of infections. We report the correlation between Cylex ImmuKnow (ng/mL ATP) values and various infectious syndromes in a large prospective cohort of lung transplant recipients., Methods: We followed up 175 lung transplants that developed 129 infectious episodes. Multiple logistic regression analysis was performed; generalized estimating equations were used to determine the odds ratio for infections., Results: The median ImmuKnow values in cytomegalovirus disease (49.3 ng/mL ATP), viral infection (70 ng/mL ATP), and bacterial pneumonia (92 ng/mL ATP) were significantly different from stable state (174.8 ng/mL ATP). The median ImmuKnow values of fungal disease (85 ng/mL ATP) and tracheobronchitis (123 ng/mL ATP) had a tendency to be lower than stable state (P=0.10), whereas patients with fungal colonization had comparable ImmunKnow values (167 vs. 174.8 ng/mL ATP). Of the patients colonized with fungus who subsequently developed fungal disease within 100 days, the median value of ImmuKnow was significantly lower than in those who did not develop fungal disease (22.5 vs. 183.5 ng/mL ATP; P<0.0001). Generalized estimating equation regression analysis showed ImmuKnow values less than or equal to 100 ng/mL ATP to be an independent predictor of infections (odds ratio 2.81)., Conclusions: Cylex ImmuKnow assay monitoring has the potential to identify the patients at risk of developing infection and those colonized with fungus that are at risk of developing disease.

Inadequate empirical antibiotic therapy for serious Pseudomonas aeruginosa infections has been linked to increased mortality. We performed a retrospective cohort study of consecutive patients with ventilator-associated pneumonia, bacteraemia or other sterile-site infections caused by P. aeruginosa occurring during Intensive Care Unit admissions. One hundred and fifty-eight episodes of serious infection with P. aeruginosa occurred in 140 patients. Empirical antibiotic therapy was microbiologically adequate in 67% of episodes of infection. Patients with P. aeruginosa isolates resistant to piperacillin/tazobactam or cefepime were more likely to have received these antibiotics in the month prior to the P. aeruginosa infection or to have had a Gram-negative bacillus resistant to these antibiotics isolated in the month prior to the P. aeruginosa infection. From these data, we have developed simple algorithms for empirical antibiotic choice in seriously ill patients with suspected P. aeruginosa infections based on prior antibiotic exposure and prior isolation of antibiotic-resistant organisms. Application of these algorithms would have improved the adequacy of empirical antibiotic therapy from 67% to 80-84%. Routine empirical addition of amikacin to the beta-lactam would have increased the adequacy of the antibiotics to 96%. We conclude that knowledge of the prior receipt of beta-lactam antibiotics with activity against P. aeruginosa and the isolation of Gram-negative bacilli resistant to such antibiotics in the recent past can readily increase the adequacy of empirical antibiotic therapy for suspected P. aeruginosa infections.

It is well established that grooming underpins sociality in group-living primates, and a number of studies have documented the stress-reducing effects of being groomed. In this study, we quantified grooming behaviour and physiological stress (assessed by faecal glucocorticoid analysis) in free-ranging Barbary macaques, Macaca sylvanus. Our results indicate that it is the giving rather than the receiving of grooming that is associated with lower stress levels. These findings shed important new light on the benefits of this key behaviour in primate social life.

Background: Surveillance studies have shown that <0.1% of coagulase-negative staphylococci are linezolid resistant; however, at our institution, 4% of such organisms were found to be resistant. We investigated the risk factors for and the epidemiological profile of linezolid-resistant coagulase-negative staphylococci., Methods: Susceptibility testing and pulsed-field gel electrophoresis were performed to analyze the genetic relatedness of both linezolid-resistant and linezolid-susceptible isolates. Clinical data were retrieved from medical records, and a case-case-control study was performed to identify unique risk factors for linezolid resistance., Results: Isolates recovered from 25 patients with linezolid-resistant coagulase-negative staphylococci were examined; all but 1 of the isolates were identified as Staphylococcus epidermidis, and all but 1 had a minimum inhibitory concentration of linezolid of >256 microg/mL. Pulsed-field gel electrophoresis showed that 21 (84%) of 25 linezolid-resistant isolates exhibited genetic relatedness, whereas linezolid-susceptible isolates were of diverse clones. Unique, independent predictors of linezolid resistance included receipt of linezolid in the 3 months preceding isolation of the coagulase-negative staphylococci (odds ratio, 20.6; 95% confidence interval, 5.8-73.0)., Conclusion: Linezolid-resistant coagulase-negative staphylococci have emerged at our institution and are predominately of a single clone. We believe that the most likely scenario to explain this emergence is that person-to-person spread of linezolid-resistant coagulase-negative staphylococci led to establishment of skin colonization with the strain. Subsequent use of linezolid was followed by selection of the linezolid-resistant strain, which then became the dominant skin flora. The potential for a parallel scenario involving clonal dissemination followed by selection of linezolid-resistant methicillin-resistant Staphylococcus aureus is a real possibility.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

After increasing from 1995 to 1999, invasive erythromycin-nonsusceptible Streptococcus pneumoniae rates per 100,000 decreased 53.6% in children from Baltimore, Maryland (US), from 1999 to 2001, which was partially attributed to strains related to the mefE-carrying England14-9 clone. The decline in infection rates was likely due to the pneumococcal 7-valent conjugate vaccine.

Background and Objective: Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak., Methods: A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed., Results: On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes., Conclusions: Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak

Adventure travel is becoming more popular, increasing the likelihood of contact with unusual pathogens. We investigated an outbreak of leptospirosis in "Eco-Challenge" multisport race athletes to determine illness etiology and implement public health measures. Of 304 athletes, we contacted 189 (62%) from the United States and 26 other countries. Eighty (42%) athletes met our case definition. Twenty-nine (36%) case-patients were hospitalized; none died. Logistic regression showed swimming in the Segama River (relative risk [RR]=2.0; 95% confidence interval [CI]=1.3 to 3.1) to be an independent risk factor. Twenty-six (68%) of 38 case-patients tested positive for leptospiral antibodies. Taking doxycycline before or during the race was protective (RR=0.4, 95% CI=0.2 to 1.2) for the 20 athletes who reported using it. Increased adventure travel may lead to more frequent exposure to leptospires, and preexposure chemoprophylaxis for leptospirosis (200 mg oral doxycycline/week) may decrease illness risk. Efforts are needed to inform adventure travel participants of unique infections such as leptospirosis.

We examined outbreak investigations conducted around the world from 1988 to 1999 by the Centers for Disease Control and Prevention's Epidemic Intelligence Service. In 44 (4.0%) of 1,099 investigations, identified causative agents had bioterrorism potential. In six investigations, intentional use of infectious agents was considered. Healthcare providers reported 270 (24.6%) outbreaks and infection control practitioners reported 129 (11.7%); together they reported 399 (36.3%) of the outbreaks. Health departments reported 335 (30.5%) outbreaks. For six outbreaks in which bioterrorism or intentional contamination was possible, reporting was delayed for up to 26 days. We confirmed that the most critical component for bioterrorism outbreak detection and reporting is the frontline healthcare profession and the local health departments. Bioterrorism preparedness should emphasize education and support of this frontline as well as methods to shorten the time between outbreak and reporting.

We investigated an outbreak of leptospirosis among athletes and community residents after a triathlon was held in Springfield, Illinois. A telephone survey was conducted to collect clinical information and data on possible risk factors, community surveillance was established, and animal specimens and lake water samples were collected to determine the source of the leptospiral contamination. A total of 834 of 876 triathletes were contacted; 98 (12%) reported being ill. Serum samples obtained from 474 athletes were tested; 52 of these samples (11%) tested positive for leptospirosis. Fourteen (6%) of 248 symptomatic community residents tested positive for leptospirosis. Heavy rains that preceded the triathlon are likely to have increased leptospiral contamination of Lake Springfield. Among athletes, ingestion of 1 or more swallows of lake water was a predominant risk factor for illness. This is the largest outbreak of leptospirosis that has been reported in the United States. Health care providers and occupational and recreational users of bodies of freshwater in the United States should be aware of the risk of contracting leptospirosis, particularly after heavy rains.

Background: Neisseria meningitidis is a leading cause of bacterial meningitis in US; new capsular type-specific conjugate vaccines offer an opportunity for improved control of meningococcal disease. We evaluated the relative burdens of invasive meningococcal disease in US and examined the projected impact of various meningococcal conjugate vaccination strategies on rates of meningococcal disease., Methods: Meningococcal disease incidence rates were determined from active, population-based surveillance in selected US areas. Models were created to determine impact of vaccination of infants, toddlers, adolescents or college students with meningococcal conjugate vaccines, with assumptions for vaccine coverage, efficacy and duration of protection. Although we examined possible conjugate vaccine formulations including serogroups A, C, Y and W-135, the final vaccine impact analysis excluded serogroups A and W-135. Outcome measures were cumulative meningococcal disease incidence, and incidence 10 years after initiating vaccination among 0-22-year-olds., Results: In models of serogroup C+Y meningococcal conjugate vaccination of infants, toddlers and adolescents, the cumulative incidence of meningococcal disease was reduced by 54, 48 and 25%, respectively; the toddler strategy had the greatest impact per dose. After 10 years of routine meningococcal conjugate vaccination, meningococcal disease could be reduced by 50% and deaths by 64%., Conclusions: Use of meningococcal conjugate vaccine could markedly reduce meningococcal disease incidence. Our data, along with vaccine formulation and vaccination program considerations, will be important in determining the optimal choice of vaccination strategy.

Context: Elevated rates of meningococcal disease were noted among 18- to 22-year-olds in the mid-1990s. However, national data on rates of meningococcal disease in US college students were not collected until 1998., Objectives: To determine rates of meningococcal disease in US college students and to identify risk factors for meningococcal disease in this population., Design, Setting, and Patients: Prospective surveillance study with nested case-control study of US college students with meningococcal infection from September 1, 1998, to August 31, 1999. Fifty state health departments and 231 college health centers participated., Main Outcome Measures: Incidence of and risk factors for meningococcal disease in US college students., Results: Ninety-six cases of meningococcal disease were identified. The incidence rate for undergraduates was 0.7 per 100 000 persons vs 1.4 per 100 000 for the general population of 18- to 23-year-old nonstudents (P<.001). Freshmen living in dormitories had the highest incidence rate at 5.1 per 100 000. Of the 79 case-patients for whom information was available, 54 (68%) had illness due to vaccine-preventable meningococcal serogroups. On multivariable analysis of case-control study data, freshmen who lived in dormitories had an elevated risk of meningococcal disease (matched odds ratio, 3.6; 95% confidence interval, 1.6-8.5; P =.003) compared with other college students., Conclusions: Freshmen who live in dormitories have an independent, elevated risk of meningococcal disease compared with other college students. Use of the currently available quadrivalent polysaccharide vaccine among college students could substantially decrease their risk of meningococcal disease.

New meningococcal vaccines are undergoing clinical trials, and changes in the epidemiologic features of meningococcal disease will affect their use. Active laboratory-based, population-based US surveillance for meningococcal disease during 1992-1996 was used to project that 2400 cases of meningococcal disease occurred annually. Incidence was highest in infants; however, 32% of cases occurred in persons >/=30 years of age. Serogroup C caused 35% of cases; serogroup B, 32%; and serogroup Y, 26%. Increasing age (relative risk [RR], 1.01 per year), having an isolate obtained from blood (RR, 4.5), and serogroup C (RR, 1.6) were associated with increased case fatality. Among serogroup B isolates, the most commonly expressed serosubtype was P1.15; 68% of isolates expressed 1 of the 6 most common serosubtypes. Compared with cases occurring in previous years, recent cases are more likely to be caused by serogroup Y and to occur among older age groups. Ongoing surveillance is necessary to determine the stability of serogroup and serosubtype distribution.

Elevated titers of anti-myelin basic protein (anti-MBP) are highly associated with acute idiopathic unilateral optic neuritis as well as acute relapses of multiple sclerosis (MS). During acute phases of optic neuritis, free/bound antibody ratios are generally above unity, with high titers of free anti-MBP and relatively low or undetectable values of bound antibody. Three to 5 months after the acute phase when the majority of patients have recovered, free/bound anti-MBP ratios are below unity with low titers of free antibody and relatively higher levels of bound anti-MBP. Anti-MBP purified from cerebrospinal fluid of patients with optic neuritis are neutralized by synthetic peptides of human MBP containing overall amino acid residues 61-106 and do not react with synthetic peptides corresponding to residues 1-60 and 107-170. Anti-MBP may either have multiple epitopes in the region corresponding to residues 61-106 or it may react with a discontinuous epitope in this range. The mechanism of the optic nerve demyelination may be associated with anti-MBP binding in situ to MBP in the 61-106 amino acid region.