Elizabeth A. Talbot

Dynamic antibody responses to the Mycobacterium tuberculosis proteome

Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis (TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host–pathogen interactions leading to biomarker expression. Here we report a systems immunology approach integrating clinical data and bacterial metabolic and regulatory information with high-throughput detection in human serum of antibodies to the entire Mycobacterium tuberculosis proteome. Sera from worldwide TB suspects recognized approximately 10% of the bacterial proteome. This result defines the M. tuberculosis immunoproteome, which is rich in membrane-associated and extracellular proteins. Additional analyses revealed that during active tuberculosis (i) antibody responses focused on an approximately 0.5% of the proteome enriched for extracellular proteins, (ii) relative target preference varied among patients, and (iii) responses correlated with bacillary burden. These results indicate that the B cell response tracks the evolution of infection and the pathogen burden and replicative state and suggest functions associated with B cell-rich foci seen in tuberculous lung granulomas. Our integrated proteome-scale approach is applicable to other chronic infections characterized by diverse antibody target recognition.

Variability in the Hawthorne Effect With Regard to Hand Hygiene Performance in High‐ and Low‐Performing Inpatient Care Units

UNLABELLEDnOBJECTIVE. To determine the impact of known observers on hand hygiene performance in inpatient care units with differing baseline levels of hand hygiene compliance.nnnDESIGNnObservational study.nnnSETTINGnThree inpatient care units, selected on the basis of past hand hygiene performance, in a hospital where hand hygiene observation and feedback are routine.nnnPARTICIPANTSnThree infection control practitioners (ICPs) and a student intern observed hospital staff.nnnMETHODSnBeginning in late 2005, the 3 ICPs, who were well known to the hospital staff, performed frequent, regular observations of hand hygiene in all 3 inpatient care units of the hospital, as part of routine surveillance. During the study period (January-May 2007), a student intern who was unknown to the hospital staff also performed observations of hand hygiene in the 3 inpatient care units. The rates of hand hygiene compliance observed by the 3 ICPs were compared with those observed by the student intern.nnnRESULTSnThe 3 ICPs observed 332 opportunities for hand hygiene during 15 observation periods, and the student intern observed 355 opportunities during 19 observation periods. The overall rate of hand hygiene compliance observed by the ICPs was 65% (ie, in 215 of the 332 opportunities, the performance of proper hand hygiene by hospital staff was observed), and the overall rate of hand hygiene compliance observed by the student intern was 58% (ie, in 207 of the 355 opportunities, the performance of proper hand hygiene by hospital staff was observed) (P=.1 ). Both the ICPs and the student intern were able to distinguish between inpatient care units with a high rate of hand hygiene compliance (hereafter referred to as high-performing units) and those with a low rate (hereafter referred to as low-performing units). However, in the 2 high-performing units, the ICPs observed significantly higher compliance rates than did the student intern, whereas in the low-performing unit, both the ICPs and the student intern measured similarly low rates of hand hygiene compliance.nnnCONCLUSIONSnRecognized observers are associated with higher rates of hand hygiene compliance, even in a healthcare setting where such observations have become routine. This effect (ie, the Hawthorne effect) is more pronounced in high-performing units and insignificant in low-performing units. The use of unrecognized observers may be important for verifying high performance but is probably unnecessary for documenting poor performance. Moreover, the Hawthorne effect may be a useful tool for sustaining and improving hand hygiene compliance.

The safety of immunizing with tetanus-diphtheria-acellular pertussis vaccine (Tdap) less than 2 years following previous tetanus vaccination: experience during a mass vaccination campaign of healthcare personnel during a respiratory illness outbreak.

BACKGROUNDnTdap is recommended for health care personnel (HCP) aged <65 years who received tetanus diphtheria or tetanus toxoid immunization (Td/TT) ≥2 years earlier. During a medical center Tdap vaccination campaign, we assessed the safety of use of a Td/TT to Tdap interval <2 years in HCP. We also describe reactogenicity in HCP who were aged ≥65 years or pregnant.nnnMETHODSnHCP vaccinated with Tdap were surveyed to assess time since last Td/TT (≥2 years vs. <2 years), age, pregnancy status, and injection site adverse events (AEs) during the 2 weeks after Tdap. AE rates were calculated and compared by non-inferiority analysis using a predetermined margin of 10%. We searched clinic logbooks to assess for clinically important adverse events during the 2 months after Tdap.nnnRESULTSnOf the 4524 vaccinated HCP, 2221 (49.1%) completed a safety survey which met criteria for analysis. Non-inferiority analysis found that rates of moderate and/or severe injection site AEs were not significantly greater in those vaccinated <2 years than in those vaccinated ≥2 years after previous Td/TT. Three serious adverse events were reported during the 2 months after vaccination, none in persons who were ≥65 years, pregnant or received Td/TT <2 years before.nnnCONCLUSIONSnOur findings add to the body of evidence that a short interval between Td/TT and a single dose of Tdap is safe.

Use of alcohol-based hand sanitizers as a risk factor for norovirus outbreaks in long-term care facilities in northern New England: December 2006 to March 2007

BACKGROUNDnDuring December 2006 to March 2007, a substantial increase in norovirus illnesses was noted in northern New England. We sought to identify institutional risk factors for norovirus outbreaks in northern New England long-term care facilities (LTCFs).nnnMETHODSnState health departments in Maine, New Hampshire, and Vermont distributed surveys to infection preventionists at all LTCFs in their respective states. We collected information regarding facility attributes, routine staff use of alcohol-based hand sanitizer (ABHS) versus soap and water, facility cleaning practices, and occurrence of any acute gastroenteritis outbreaks during December 2006 to March 2007. Norovirus confirmation was conducted in public health laboratories. Data were analyzed with univariate and logistic regression methods.nnnRESULTSnOf 160 facilities, 91 (60%) provided survey responses, with 61 facilities reporting 73 outbreaks; 29 were confirmed norovirus. Facilities reporting that staff were equally or more likely to use ABHS than soap and water for routine hand hygiene had higher odds of an outbreak than facilities with staff less likely to use ABHS (adjusted odds ratio, 6.06; 95% confidence interval: 1.44-33.99).nnnCONCLUSIONnThis study suggests that preferential use of ABHS over soap and water for routine hand hygiene might be associated with increased risk of norovirus outbreaks in LTCFs.

Test characteristics of urinary lipoarabinomannan and predictors of mortality among hospitalized HIV-infected tuberculosis suspects in Tanzania.

Background Tuberculosis is the most common cause of death among patients with HIV infection living in tuberculosis endemic countries, but many cases are not diagnosed pre-mortem. We assessed the test characteristics of urinary lipoarabinomannan (LAM) and predictors of mortality among HIV-associated tuberculosis suspects in Tanzania. Methods We prospectively enrolled hospitalized HIV-infected patients in Dar es Salaam, with ≥2 weeks of cough or fever, or weight loss. Subjects gave 2 mLs of urine to test for LAM using a commercially available ELISA, ≥2 sputum specimens for concentrated AFB smear and solid media culture, and 40 mLs of blood for culture. Results Among 212 evaluable subjects, 143 (68%) were female; mean age was 36 years; and the median CD4 count 86 cells/mm3. 69 subjects (33%) had culture confirmation of tuberculosis and 65 (31%) were LAM positive. For 69 cases of sputum or blood culture-confirmed tuberculosis, LAM sensitivity was 65% and specificity 86% compared to 36% and 98% for sputum smear. LAM test characteristics were not different in patients with bacteremia but showed higher sensitivity and lower specificity with decreasing CD4 cell count. Two month mortality was 64 (53%) of 121 with outcomes available. In multivariate analysis there was significant association of mortality with absence of anti-retroviral therapy (pu200a=u200a0.004) and a trend toward association with a positive urine LAM (pu200a=u200a0.16). Among culture-negative patients mortality was 9 (75%) of 12 in LAM positive patients and 27 (38%) of 71 in LAM negative patients (pu200a=u200a0.02). Conclusions Urine LAM is more sensitive than sputum smear and has utility for the rapid diagnosis of culture-confirmed tuberculosis in this high-risk population. Mortality data raise the possibility that urine LAM may also be a marker for culture-negative tuberculosis.

Common Ground for the Control of Multidrug-Resistant Salmonella in Ground Beef

A strategy to combat multidrug-resistant (MDR) Salmonella in ground beef is urgently needed. A national multi-disciplinary meeting reviewed the epidemiology of MDR Salmonella infection and contamination in humans, animals, and retail meat. In spite of a recent overall decrease in human MDR Salmonella isolates, certain types, such as Salmonella enterica serotype Newport multidrug-resistant-AmpC strain and Salmonella enterica serotype Typhimurium definitive type (DT) 104, have persisted, and several recent large outbreaks of human infection have occurred. Key agencies that contribute to a safe ground beef supply were represented at the meeting and contributed to the discussion of possible control strategies from the farm to the table. Several of the control strategies suggested are unpopular to some, including restricting the use of antimicrobial agents in food animals, designation of multidrug-resistant Salmonella as an adulterant in ground beef, and improving the mechanisms for product trace-back investigations. Nevertheless, enhanced farm-based animal infection control, judicious veterinary and human antibiotic use, regulatory controls, and consumer practices will lead to important industry, veterinary, and public health outcomes.

Travel Medicine Research Priorities: Establishing an Evidence Base

BACKGROUNDnTravel medicine is the medical subspecialty which promotes healthy and safe travel. Numerous studies have been published that provide evidence for the practice of travel medicine, but gaps exist.nnnMETHODSnThe Research Committee of the International Society of Travel Medicine (ISTM) established a Writing Group which reviewed the existing evidence base and identified an initial list of research priorities through an interactive process that included e-mails, phone calls, and smaller meetings. The list was presented to a broader group of travel medicine experts, then was presented and discussed at the Annual ISTM Meeting, and further revised by the Writing Group. Each research question was then subject to literature search to ensure that adequate research had not already been conducted.nnnRESULTSnTwenty-five research priorities were identified and categorized as intended to inform pre-travel encounters, safety during travel, and post-travel management.nnnCONCLUSIONnWe have described the research priorities that will help to expand the evidence base in travel medicine. This discussion of research priorities serves to highlight the commitment that the ISTM has in promoting quality travel-related research.

Outbreak of Skin Infections in College Football Team Members Due to an Unusual Strain of Community-Acquired Methicillin-Susceptible Staphylococcus aureus

ABSTRACT We report a skin and soft-tissue infection outbreak among football team members due to a USA300 methicillin-susceptible Staphylococcus aureus (MRSA) strain with genes coding for Panton-Valentine leukocidin and the arginine catabolic mobile element. We postulate that the strain is a community-associated USA300 MRSA strain that lost methicillin resistance but retained important virulence factors.

Performance of the OraQuick HCV Rapid Antibody Test for Screening Exposed Patients in a Hepatitis C Outbreak Investigation

ABSTRACT During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.

Adapting and Implementing a Community Program to Improve Retention in Care among Patients with HIV in Southern Haiti: “Group of 6”

Objective. In Mozambique, a patient-led Community ART Group model developed by Médecins Sans Frontières improved retention in care and adherence to antiretroviral therapy (ART) among persons with HIV. We describe the adaptation and implementation of this model within the HIV clinic located in the largest public hospital in Haitis Southern Department. Methods. Our adapted model was named Group of 6. Hospital staff enabled stable patients with HIV receiving ART to form community groups with 4–6 members to facilitate monthly ART distribution, track progress and adherence, and provide support. Implementation outcomes included recruitment success, participant retention, group completion of monthly monitoring forms, and satisfaction surveys. Results. Over one year, 80 patients from nine communities enrolled into 15 groups. Six participants left to receive HIV care elsewhere, two moved away, and one died of a non-HIV condition. Group members successfully completed monthly ART distribution and returned 85.6% of the monthly monitoring forms. Members reported that Group of 6 made their HIV management easier and hospital staff reported that it reduced their workload. Conclusions. We report successful adaptation and implementation of a validated community HIV-care model in Southern Haiti. Group of 6 can reduce barriers to ART adherence, and will be integrated as a routine care option.