Low Prevalence Settings Research Articles

“It was giving them a feeling that they're not alone in this”: Perspectives of caregivers and clinicians on a camp for UK adolescents with HIV

There are a number of challenges for adolescents living with perinatally acquired HIV (PAH), including adherence to antiretroviral medication and managing HIV stigma. Offering psychosocial interventions residentially (camps) is one approach offered to some adolescents with chronic illness as a way to reduce isolation, increase self-esteem and wellbeing, enhance medication adherence and increase condition- specific knowledge. There have been studies on the experiences of young people with HIV who have attended camps but no studies exploring the view of other key informants. Examining the perceptions of caregivers and clinicians of young people with PAH who have attended camps may provide a fuller picture of the experience and impact of camps for young people, allowing for corroboration or comparison between the views of different informants. We interviewed seven caregivers and eight clinicians of eleven young people who had attended a UK intensive support camp, analysing data using thematic analysis. These eleven young people had been sampled representatively. Participants referred to expectations that they had before the young person had attended camp, their perception of the young person's experience there, as well as the perceived impact of the camp. Perceived benefits of the camp covered social (relationships and communication), psychological (independence, empowerment, confidence), cognitive (HIV knowledge), and health behaviour (ART adherence) domains. The study revealed benefits of camps that corroborate the views of young people. Future studies could explore the similarities and differences in experiences between low and high HIV prevalence settings.

Deep-Learning Based Automated Detection Algorithm for Active Pulmonary Tuberculosis on Chest Radiographs: Diagnostic Performance in Systematic Screening of Asymptomatic Individuals

Background: Performance of deep-learning based automated detection (DLAD) algorithms in systematic screening for active pulmonary tuberculosis is unknown. We aimed to validate DLAD algorithm for detection of active pulmonary tuberculosis and any radiologicallyidentifiable relevant abnormality on chest radiographs (CRs) in this setting. Methods: We performed out-of-sample testing of a trained DLAD algorithm, using CRs from 19,686 asymptomatic individuals (male: 19,475, female: 211; mean ± standard deviation: 21.3 ± 1.9 years) as part of systematic screening for tuberculosis between January 2013 and July 2018. Area under the receiver operating characteristic curves (AUC) of DLAD for diagnosis of tuberculosis and any relevant abnormalities were measured. Accuracy measures including sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs) were calculated at predefined operating thresholds (high sensitivity threshold, 0·16; high specificity threshold, 0·46). Findings: All five CRs with active pulmonary tuberculosis were correctly classified as having abnormal findings by DLAD with specificities of 0·959 and 0·997, PPVs of 0·006 and 0·068, and NPVs of both 1·000 at high sensitivity and high specificity thresholds, respectively. With high specificity thresholds, DLAD showed comparable diagnostic measures for tuberculosis to the pooled radiologists (P values > 0·05). For the detection of any radiologically-identifiable relevant abnormality (n=28), DLAD showed AUC value of 0·967 (95% confidence interval, 0·938-0·996) with sensitivities of 0·821 and 0·679, specificities of 0·960 and 0·997, PPVs of 0·028 and 0·257, and NPVs of both 1·000 at high sensitivity and high specificity thresholds, respectively. Interpretation: In systematic screening for tuberculosis in a lowprevalence setting, DLAD algorithm demonstrated excellent diagnostic performance, comparable to the radiologists in the detection of active pulmonary tuberculosis. Funding Statement: This study was supported by the Seoul Research & Business Development Program (grant number: FI170002), and Lunit Inc. provided technical supports for this study. Declaration of Interests: There is a major research agreement between Seoul National University Hospital and Lunit Inc, in which roles of researchers and Lunit Inc. were described. However, the funder and Lunit Inc. did not have any role either in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the article for publication. Researchers (J.H.L., E.J.H., W.Y.L., S.L., J.R.A.) who controlled, manipulated and analyzed data, did not have any conflict of interest. Three authors (J.M.G., H.K., C.M.P.) received research grants from Lunit Inc. for outside of this study. Ethics Approval Statement: This retrospective study was approved by the institutional review board of The Armed Forces Medical Command of Korea, and the requirement for informed consent was waived.

Report of a Leprosy case in Singapore: an age-old disease not to be forgotten in developed countries with low-prevalence settings

Introduction Leprosy is rarely reported in developed countries with low-prevalence settings. Its diagnosis may be missed due to its low frequency in non-endemic regions, as well as its long incubation period. The report describes an imported leprosy case of a healthcare worker in Singapore.Case presentation A Filipino nursing personnel presented with a persistent non-tender erythematous plaque over his right upper back for many years despite topical treatment. He had the lesion before coming to Singapore but decided to seek medical consultation only after the lesion progressed with new erythematous papules developing over his face, trunk and upper limbs. Punch biopsies of skin lesions revealed fite-positive bacilli, which were identified to be Mycobacterium leprae by GenoType LepraeDR v1 assay (Hain LifeScience, Germany). No mutation was detected at rpoB (rifampicin), gyrA (ofloxacin) and folP1 (dapsone) gene targets. He was started on multi-drug therapy and responded to the treatment. The only prolonged close contact he had was his housemate who was screened and given a single dose of rifampicin as chemoprophylaxis.Conclusion In non-endemic settings, awareness is crucial in diagnosing leprosy. The availability of molecular testing and multi-disciplinary management are essential in the confirmation and control of this disease of public health importance.

Performance of an Ultra-Sensitive Assay Targeting the Circulating Anodic Antigen (CAA) for Detection of Schistosoma mansoni Infection in a Low Endemic Area in Brazil.

Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings, where the conventional parasitological methods are insensitive. We determined the accuracy of an up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay in urine and serum for Schistosoma mansoni diagnosis in low-prevalence settings in Ceará, Brazil, before and after praziquantel treatment. Clinical samples of a total of 258 individuals were investigated by UCP-LF CAA, point-of-care—circulating cathodic antigen (POC-CCA), soluble worm antigen preparation (SWAP)-ELISA and Kato-Katz (KK); a selection of 128 stools by real-time PCR technique. Three and 6-weeks after treatment, samples were collected and evaluated by detection Schistosoma circulating antigens (CAA and CCA). The UCP-LF CAA assays detected 80 positives (31%) with urine and 82 positives (31.8%) with serum. The urine POC-CCA and serum SWAP-ELISA assays detected 30 (11.6%) and 107 (40.7%) positives, respectively. The Kato-Katz technique revealed only 4 positive stool samples (1.6%). Among the 128 individuals with complete data records, 19 cases were identified by PCR (14.8%); Sensitivities and specificities of the UCP-LF CAA assays, determined versus a combined reference standard based on CCA/KK/PCR positivity, ranged from 60–68% to 68–77%, respectively. In addition only for comparative purposes, sensitivities of the different assays were determined vs. a comparative reference based on CAA/KK/PCR positivity, showing the highest sensitivity for the urine CAA assay (80%), followed by the serum CAA (70.9%), SWAP-ELISA (43.6%), PCR (34.5%), POC-CCA (29.1%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (3.6%). CAA concentrations were higher in serum than in urine and were significantly correlated. There was a significant decrease in urine and serum CAA levels 3 and 6-weeks after treatment. The UCP-LF CAA assays revealed 33 and 28 S. mansoni-infected patients at the 3- and 6-week post-treatment follow-up, respectively. The UCP-LF CAA assays show high sensitivity for the diagnosis of S. mansoni in low-endemicity settings. It detects a considerably higher number of infections than microscopy, POC-CCA or PCR. Also it shows to be very useful for evaluating cure rates after treatment. Hence, the UCP-LF CAA assay is a robust and promising diagnostic approach in low-transmission settings.

Children delivered via cesarean section had a lower risk of developing caries than those delivered vaginally in a low caries prevalence setting

Children delivered via cesarean section had a lower risk of developing caries than those delivered vaginally in a low caries prevalence setting

A model to promote the uptake of male circumcision as an HIV-preventive measure in high HIV and low male circumcision prevalence settings.

BackgroundHuman immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) remain the leading global burden of disease, especially in Southern Africa. As such, efforts to develop innovative preventive and curative measures continue to be a global priority. Of late, the World Health Organization recognised and recommended mass male circumcision (MC) as an adjunct HIV-preventive measure in 14 selected sub-Sahara African countries. However, despite efforts to promote the uptake of MC in these countries, the uptake remains significantly below set targets.AimThe purpose of this article is to describe the process that was followed in developing, describing and evaluating a model to promote the uptake of MC as an HIV-preventive measure in high HIV and low MC settings.SettingThe model is designed for all settings of high HIV and low MC prevalence.MethodA theory-generative, qualitative, exploratory, descriptive and contextual research design was used. The process involved four distinct steps, namely concept analysis, description of relationship statements, and description and evaluation of the model using the criteria of clarity, simplicity, generality, accessibility and importance.ResultsThe central concept was identified as ‘promote the uptake of MC’, and three integral constituents were identified for the process, such as transforming men’s mindsets about MC, facilitating accessibility and utilisation of MC services, and maintaining a supportive social system. These formed the basis for the model.ConclusionThe model provides a framework of reference for healthcare providers in promoting the uptake of MC as an HIV-preventive measure in high HIV and low MC settings.

A signal-to-cutoff ratio in the roche elecsys HIV Ag/Ab assay to predict confirmed HIV-1 infection in a low-prevalence setting

A signal-to-cutoff ratio in the roche elecsys HIV Ag/Ab assay to predict confirmed HIV-1 infection in a low-prevalence setting

Response to First-Line Antiretroviral Therapy Among PLHIV from a High-Risk, Low-Prevalence Setting

The study reports the response of first-line antiretroviral therapy (ART) by assessing CD4 and CD8 T-lymphocyte and viral load (VL) among Bangladeshi people living with HIV (PLHIV). This observational approach was conducted on 100 PLHIVs, grouped into therapy naive (n = 33), therapy initiators with CD4 T-cell count of <350 cells/µL (n = 33), and therapy receivers for >1 year prior to the study period (n = 34). Therapy initiators who continued the study (n = 20) were followed up after 12 and 24 weeks of therapy initiation. The CD4 and CD8 T-lymphocyte count estimation and (VL) were quantified. The mean CD4 T-lymphocyte count was significantly reduced among the therapy initiators in comparison to therapy naive and therapy receivers. Similar findings were observed for CD8 T-lymphocyte count among the study groups. The mean HIV-1 RNA VL among therapy initiators showed a significant decrease after 12 and 24 weeks, and 85% patients in this group obtained undetectable VL status indicating the good therapeutic outcome.

Mycobacterial Infections in Patients With Chronic Kidney Disease and Kidney Transplantation.

Patients with chronic kidney disease have impaired immunity that increases their risk of infection. Increased incidence of mycobacterial infections, in particular Mycobacterium tuberculosis, is described in patients undergoing hemodialysis and peritoneal dialysis as well as after kidney transplantation in low-prevalence and high-prevalence settings. Diagnosis of this infection can be challenging because of atypical presentations that may lead to treatment delay and, consequently, increased mortality; however, recent advances in molecular testing have improved diagnostic accuracy. It is imperative to try to identify those patients at increased risk and offer adequate prophylaxis. There are controversies and insufficient data regarding treatment agents, duration, and dosages. Most studies in nontuberculous mycobacteria are based on case series and retrospective studies.

The epidemiology of HCV infection in patients with advanced CKD/ESRD: A global perspective

Liver disease in patients with chronic kidney disease (CKD) is most commonly due to hepatitis C virus (HCV) and contributes to increased rates of mortality. Among the pre-dialysis population, the estimated prevalence of anti-HCV positivity is based on few, limited-size studies. In hemodialysis patients however, HCV remains very prevalent despite large declines in seropositivity rates in dialysis facilities in developed countries after preventive measures were adopted in the 1990s. Recent surveys indicate that the HCV seropositivity prevalence ranges from 1.4%-28.3%, and 4.7%-41.9%, among maintenance dialysis patients in developed and developing countries respectively. Although the full extent of dialysis unit-associated HCV transmission is unknown, outbreaks continue to occur, regardless of health system infrastucture. According to US Centers for Disease Control data, over 50% of health care-associated HCVoutbreaks reported from 2008 to 2015 occurred within dialysis facilities. Strict adherence to infection control procedures and routine serologic screening plays a pivotal role in preventing transmission of HCV within hemodialysis units, even in the setting of low HCV prevalence. With the advent of directly acting antivirals, cure of HCV-infected patients on maintenance hemodialysis will help reduce transmission within units and further lower the frequency of HCV infection.

766. Migration Flows and Increase of Extrapulmonary Tuberculosis in a Low Prevalence Setting: A Retrospective Analysis in Two Italian Centers

BackgroundExtrapulmonary tuberculosis (EPTB) represents 25% of Worldwide tuberculosis and it is more commonly associated with immunodepression. The purpose of this study was to determinate the burden of EPTB in a low TB prevalence setting.MethodsA retrospective evaluation of patients treated for TB at Tor Vergata Hospital and Terni Hospital (Italy) from January 2013 to November 2017 was done. Clinical charts, laboratory tests and radiological findings were reviewed and analysed. Data were elaborated using Yates’ method analysis, Fisher test and Pearson’s chi-square test.ResultsA total of 171 patients were enrolled from 2013 to 2017 in two Italian centers (Rome and Terni); 71% were males, with a mean age of 41.5 years. The number of TB diagnosis increased among the study period (6.6% in 2013 vs. 56% in 2017) and an increase of EPTB (23% in 2013 vs. 44% in 2017) was seen. Most commonly EPTB presented as generalized lymphadenitis (34%), osteomyelitis and spondylodiscitis (28%) and other sites localizations (31%). Statistical analysis revealed a significant correlation between geographical provenience and TB localization (P = 0.004). Extra European immigrants (76% Africans) resulted at higher risk of EPTB (OR 2.31; CI 95% 0.63–8.46), while being Caucasian showed a protective role toward EPTB development (P = 0.001). The risk of EPTB doubled in 2015–2017 respect 2013–2014.ConclusionFrom 2013 to 2017 an increase in TB admissions was documented with a significant higher number of EPTB cases, particularly in extra-European immigrants. The doubled risk in 2015–2017 was likely the consequence of the recent ongoing escalating levels of migration from African countries and may result as an emerging Public Health problem.Disclosures All authors: No reported disclosures.

793. Diagnostic Accuracy of Single vs. Multiple Gene Xpert for Discontinuation of Airborne Infection Isolation in Suspected Pulmonary Tuberculosis Patients at a US Safety-Net Hospital

BackgroundPatients suspected to have pulmonary tuberculosis (PTB) undergo serial sputum analysis under airborne infection isolation (AII). The US FDA approved the Cepheid GeneXpert-MTB-Rif® to support removing patients from AII. The FDA requires that “either one or two” separate sputum specimens be examined. To clarify this statement, the National Tuberculosis Controllers’ Association and the Association of Public Health Laboratories published guidelines that recommend that two sputum specimens be used and recommend that each institution examine their own data to determine whether one specimen is sufficient. Most patients in low prevalence settings do not have PTB yet are tested several times; an optimal testing strategy will reduce unnecessary isolation and related expenses. We sought to determine the diagnostic accuracy of a single vs. two sputum samples for Xpert MTB/RIF in discharging suspected PTB patients from AII.MethodsRetrospective review of patients admitted between September 2016 to January 2018 was undertaken to identify sensitivity, specificity, positive and negative predictive values, for MTB gene Xpert in comparison to Mycobacterial culture as the gold standard. We further analyzed whether a larger number of such tests improved diagnostic yield for PTB.ResultsOne hundred seventy-one patients, 17.5% of whom were HIV+, mostly of non-US origins (64%), provided 312 samples for Xpert MTB/RIF, of which 26 were Xpert-positive. These 26 samples came from 15 patients, 14 of whom were diagnosed using the first sample tested with Xpert MTB/RIF. Sensitivity and specificity of the first sample tested with Xpert MTB/RIF were more than those for the first two samples considered together or for all tested samples. Of these 15 positive cases, 13 were confirmed on sputum culture; 10 were positive from the first, one from the second, and two from the third sputum samples cultured.Test detailsSensitivitySpecificityPPVNPVFirst Sample PCR92.3% (63.97-99.81%)98.8% (95.74-99.85%)85.7%99.4%First + Second Sample PCR86.4% (65.09-97.09%)99.2% (97.16-99.90%)90.5%98.8%All Samples PCR88.9%99.3%92.3%98.9%ConclusionPatients suspected to have PTB at our facility can be rapidly and accurately discharged from AII after testing a single sputum sample for MTB/RIF Xpert.Disclosures All authors: No reported disclosures.

A new highly sensitive enzyme-linked immunosorbent assay for the detection of Plasmodium falciparum histidine-rich protein 2 in whole blood

BackgroundThe detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensitive Alere™ Malaria Ag P.f ELISA (HS ELISA) was developed to detect P. falciparum histidine-rich protein 2 (HRP2) in clinical whole blood specimens. In this study, the analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens from Karen village, Myanmar and Nagongera, Uganda.ResultsThe HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Additionally, the Z′-factor statistic of 0.862 indicates the HS ELISA as an excellent, reproducible assay, and the coefficients of variation for inter- and intra-plate testing, 11.76% and 2.51%, were acceptable. Against clinical whole blood specimens with concordant microscopic and PCR results, the HS ELISA showed 100% (95% CI 96.4–100) diagnostic sensitivity and 97.9% (95% CI 94.8–99.4) diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% (95% CI 88.4–100) and 88.9% (95% CI 70.8–97.6), respectively. The overall sensitivity and specificity for all 352 samples were 100% (CI 95% 96–100%) and 97.3% (CI 95% 94–99%).ConclusionsThe HS ELISA is a robust and reproducible assay. The findings suggest that the HS ELISA may be a useful tool as an affordable reference assay for new ultra-sensitive HRP2-based RDTs.

Treatment-refractory giardiasis: challenges and solutions.

Giardia is the commonest parasitic diarrheal pathogen affecting humans and a frequent cause of waterborne/foodborne parasitic diseases worldwide. Prevalence of giardiasis is higher in children, living in poor, low hygiene settings in developing countries, and in travelers returning from highly endemic areas. The clinical picture of giardiasis is heterogeneous, with high variability in severity of clinical disease. It can become chronic or be followed by post-infectious sequelae. An alarming increase in cases refractory to the conventional treatment with nitroimidazoles (ie, metronidazole) has been reported in low prevalence settings, such as European Union countries, especially in patients returning from Asia. In view of its relevance, we aim in this review to recapitulate present clinical knowledge about Giardia, with a special focus on the challenge of treatment-refractory giardiasis. We propose a working definition of clinically drug-resistant giardiasis, summarize knowledge regarding resistance mechanisms, and discuss its clinical management according to research-based evidence and medical practice. Advances in development and identification of novel drugs and potential non-pharmacological alternatives are also reviewed with the overall aim to define knowledge gaps and suggest future directions for research.

Healthcare-associated transmission of Panton-Valentine leucocidin positive methicillin-resistant Staphylococcus aureus: the value of screening asymptomatic healthcare workers

BackgroundThree patients hospitalised in the coronary care unit of a general district hospital (England, UK) were tested positive for Panton-Valentine leucocidin methicillin-resistant Staphylococcus aureus colonisation during their routine weekly screening for methicillin-resistant Staphylococcus aureus (MRSA). The isolates were indistinguishable and all three patients have previously had negative screening tests. The outbreak investigation team considered exploring the possibility of PVL-MRSA transmission from members of staff to the patients and potentially between members of staff.MethodAs part of the investigations, healthcare workers on coronary care unit and intensive care unit were screened for MRSA carriage.ResultsAmong 134 screened healthcare workers, five staff members (3.7%) were MRSA colonised. Among these isolates, four were Panton-Valentine leukocidin positive. However, only two healthcare workers had an indistinguishable isolate with the isolate identified among the colonised patients. Decolonisation treatment was offered to all colonised patients and healthcare workers.ConclusionIn low MRSA prevalence settings, healthcare workers may be a reservoir of MRSA and an important potential source of transmission to patients. Screening and decolonisation of colonised healthcare workers may provide a valuable strategy in managing linked hospital acquisitions and reduce the risk of occupationally acquired complications. MRSA mass screen of healthcare workers should be considered in transmission with a strain that has a potentially increased virulence, such as Panton-Valentine leucocidin methicillin-resistant Staphylococcus aureus.

Mini-Mental State Examination: diagnostic test accuracy study in primary care referrals.

To undertake a diagnostic test accuracy study of the Mini-Mental State Examination (MMSE) administered in primary care to patients who were subsequently referred to a cognitive disorders clinic in secondary care (n=72). MMSE scores from primary care were cross-classified with reference standard diagnoses made in secondary care, blind to MMSE score, in order to calculate standard measures of discrimination (including sensitivity and specificity, positive and negative predictive values). MMSE showed poor sensitivity (0.64) but better specificity (0.80) for diagnosis of any cognitive impairment at the index paper specified cut-off, with little additional benefit using a more stringent cut-off. These data suggest MMSE is not suitable for screening for cognitive impairment in the low prevalence setting of primary care.

Eliminating hepatitis C: The importance of frequent testing of people who inject drugs in high-prevalence settings.

Modelling suggests that more frequent screening of people who inject drugs (PWID) and an improved care cascade are required to achieve the WHO hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030. We determined the testing frequencies (2-yearly, annually, 6-monthly and 3-monthly) and retention in care required among PWID to achieve the HCV incidence reduction target through treatment as prevention in low (25%), medium (50%) and high (75%) chronic HCV prevalence settings. Mathematical modelling of HCV transmission among PWID, capturing testing, treatment and other features of the care cascade were employed. In low-prevalence settings, 2-yearly antibody testing of PWID was estimated to reach the elimination target by 2027-2030 depending on retention in care, with annual testing reducing the time by up to 3years. In medium-prevalence settings, if close to 90% testing coverage were achieved, then annual antibody testing of PWID would be sufficient. If testing coverage were lower (80%), 6-monthly antibody testing with at least 70% retention in care or annual HCV RNA/cAg testing would be required. In high-prevalence settings, even 3-monthly HCV RNA/cAg testing of PWID was unable to achieve the incidence reduction target. Thus, for geographical areas or subpopulations with high prevalence, WHO incidence targets are unlikely to be met without 3-monthly RNA/cAg testing accompanied by other prevention measures. Novel testing strategies, such as rapid point-of-care antibody testing or replacing antibody testing with RNA/cAg tests as a screening tool, can provide additional population-level impacts to compensate for imperfect follow-up or testing coverage.

Cytokine biomarkers for the diagnosis of tuberculosis infection and disease in adults in a low prevalence setting

ObjectiveAccurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. Methods193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α, IFN-γ, IP-10 and MIP-1β) responses, measured by Luminex multiplex immunoassay. ResultsThe background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected individuals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. ConclusionMycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected individual, and potentially between LTBI and active tuberculosis.

In-Hospital Surgery as a Risk Factor for Onset of AmpC-Producing Escherichia coli Blood Stream Infections

There has been a progressive rise in the incidence of blood stream infections (BSI) caused by multidrug-resistant Gram-negative organisms (MDR GN), which cause increased morbidity and mortality. For this reason, recent studies have focused on risk factors of acquisition of carbapenemase-producing Enterobacteriaceae and extended-spectrum beta-lactamase producers. However, there is limited data on risk factors for BSI caused by AmpC-producing Enterobacteriaceae (AmpC EC), especially in low prevalence settings such as Australia. This study was performed to identify risk factors for acquisition of AmpC E. coli, using a retrospective matched case control design over a 3-year period. Patients with BSI caused by AmpC E. coli were matched with controls (third generation cephalosporin susceptible E. coli) by age and site of infection (n = 21). There was no significant difference in age, sex, clinical outcome, time to onset of BSI, recent antibiotic use (last 3 months), comorbidities (type 2 diabetes mellitus, renal failure) intensive care unit admission, underlying hematological condition, immunosuppressant use, APACHE II score, or any recent urological procedures (within last 3 months) between the two groups. On univariate analysis, the AmpC E. coli group were more likely to have had a surgical procedure in hospital and lived in a residential aged care facility. On multivariate logistic regression analysis, a recent surgical procedure was associated with the onset of AmpC E. coli BSI (Odd’s Ratio (OR) 4.78, p = 0.034). We concluded that in a relatively low prevalence setting such as Australia, AmpC E. coli BSI is potentially associated with surgery performed in hospital due to previous antibiotic exposure and longer hospitalization.

Point-prevalence survey of carbapenemase-producing Enterobacteriaceae and vancomycin-resistant enterococci in adult inpatients in a university teaching hospital in the UK

Infections with carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant enterococci (VRE) are associated with increased morbidity and mortality, but the carriage rates of CRE and VRE among hospital inpatients are unknown. A point-prevalence survey was conducted to determine CPE and VRE carriage rates in hospitalized adults. Eight hundred and eighteen of 960 (85.2%) adult inpatients were invited to participate in the study. Of these, 595 patients (72.7%) consented and provided specimens. Of 540 samples tested, none were positive for CPE. One hundred and thirty of 540 (24.1%) samples were VRE positive, and 34 of 40 (85%) of wards had cases. Universal screening for CPE may not be cost-effective in low-prevalence settings, but targeted screening of high-risk patients should continue. The optimal screening strategy for VRE remains to be determined, as universal screening and isolation is not feasible in the study setting.