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Background: Individual-based models (IBMs) are useful to simulate events subject to stochasticity and/or heterogeneity, and have become well established to model the potential (re)emergence of pathogens (e.g., pandemic influenza, bioterrorism). Individual heterogeneity at the host and pathogen level is increasingly documented to influence transmission of endemic diseases and it is well understood that the final stages of elimination strategies for vaccine-preventable childhood diseases (e.g., polio, measles) are subject to stochasticity. Even so it appears IBMs for both these phenomena are not well established. We review a decade of IBM publications aiming to obtain insights in their advantages, pitfalls and rationale for use and to make recommendations facilitating knowledge transfer within and across disciplines.Methods: We systematically identified publications in Web of Science and PubMed from 2006-2015 based on title/abstract/keywords screening (and full-text if necessary) to retrieve topics, modeling purposes and general specifications. We extracted detailed modeling features from papers on established vaccine-preventable childhood diseases based on full-text screening.Results: We identified 698 papers, which applied an IBM for infectious disease transmission, and listed these in a reference database, describing their general characteristics. The diversity of disease-topics and overall publication frequency have increased over time (38 to 115 annual publications from 2006 to 2015). The inclusion of intervention strategies (8 to 52) and economic consequences (1 to 20) are increasing, to the detriment of purely theoretical explorations. Unfortunately, terminology used to describe IBMs is inconsistent and ambiguous. We retrieved 24 studies on a vaccine-preventable childhood disease (covering 7 different diseases), with publication frequency increasing from the first such study published in 2008. IBMs have been useful to explore heterogeneous between- and within-host interactions, but combined applications are still sparse. The amount of missing information on model characteristics and study design is remarkable.Conclusions: IBMs are suited to combine heterogeneous within- and between-host interactions, which offers many opportunities, especially to analyze targeted interventions for endemic infections. We advocate the exchange of (open-source) platforms and stress the need for consistent "branding". Using (existing) conventions and reporting protocols would stimulate cross-fertilization between research groups and fields, and ultimately policy making in decades to come. [ABSTRACT FROM AUTHOR]

Background: There is an established correlation between maternal education and reduction in childhood mortality. One proposed link is that an increase in maternal education will lead to an increase in health care access and vaccine uptake. Vaccinations are a central preventative child health tool, therefore demonstrating the importance of understanding factors that can improve coverage. This review aims to establish if there is a correlation between increasing maternal education and vaccine uptake and if this varies between continents, setting and time.Methods: An electronic database search was conducted using Medline Ovid, Embase and The Cochrane Library using a combination of keywords and appropriate MeSH terms for maternal education and child vaccination. Bibliographies were also hand searched. Data was extracted and entered onto a Microsoft Excel spreadsheet and analysed using STATA 13.0 software. The primary outcome of effect size of maternal education on completion of childhood vaccinations was analysed at different levels. Secondary outcomes were explored using subgroup analyses of differences between continents, rural or urban settings, and dates.Results: The online search yielded 3430 papers, 37 were included in this study. The analysis showed increasing child vaccination uptake with increasing maternal education. Overall, analysis showed that the odds of full childhood vaccination were 2.3 times greater in children whose mother received secondary or higher education when compared to children whose mother had no education. There was large variability in the effect size between the studies included.Conclusions: Improving maternal education is important for increasing childhood vaccination uptake and coverage. Further research is needed in higher income countries.Trial Registration: PROSPERO Registration No: CRD42016042409 . [ABSTRACT FROM AUTHOR]

Background: Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M. pneumoniae (MRMP) strains have become more common. In this study, we assessed the efficacy of tetracyclines and fluoroquinolones in MRMP treatment in children through a systematic review and meta-analysis.Methods: Two reviewers individually searched 10 electronic databases (Medline/Pubmed, Embase, the Cochrane Library, and core Korean, Chinese, and Japanese journals) for papers published from January 1, 1990 to March 8, 2018. The following data for each treatment group were extracted from the selected studies: intervention (tetracyclines and fluoroquinolones/comparator), patient characteristics (age and sex), and outcomes (fever duration, hospital stay length, treatment success rate, and defervescence rates 24, 48, and 72 h after starting treatment).Results: Eight studies involving 537 participants were included. Fever duration and hospital stay length were shorter in the tetracycline group than in the macrolide group (weighted mean difference [WMD] = - 1.45, 95% confidence interval [CI]: - 2.55 to - 0.36, P = 0.009; and WMD = - 3.33, 95% CI: - 4.32 to - 2.35, P < 0.00001, respectively). The therapeutic efficacy was significantly higher in the tetracycline group than in the macrolide group (odds ratio [OR]: 8.80, 95% CI: 3.12-24.82). With regard to defervescence rate, patients in the tetracycline group showed significant improvement compared to those in the macrolide group (defervescence rate after 24 h, OR: 5.34, 95% CI: 1.81-15.75; after 48 h, OR 18.37, 95% CI: 8.87-38.03; and after 72 h, OR: 40.77, 95% CI: 6.15-270.12). There were no differences in fever improvement within 24 h in patients in the fluoroquinolone group compared to those in the macrolide group (OR: 1.11, 95% CI: 0.25-5.00), although the defervescence rate was higher after 48 h in the fluoroquinolone group (OR: 2.78, 95% CI: 1.41-5.51).Conclusion: Tetracyclines may shorten fever duration and hospital stay length in patients with MRMP infection. Fluoroquinolones may achieve defervescence within 48 h in patients with MRMP infection. However, these results should be carefully interpreted as only a small number of studies were included, and they were heterogeneous. [ABSTRACT FROM AUTHOR]

Background: Though home-based human immunodeficiency virus (HIV) counseling and testing (HBHCT) is implemented in many sub-Saharan African countries as part of their HIV programs, linkage to HIV care remains a challenge. The purpose of this study is to test an intervention to enhance linkage to HIV care and improve HIV viral suppression among individuals testing HIV positive during HBHCT in rural Uganda.Methods: The PATH (Providing Access To HIV Care)/Ekkubo Study is a cluster-randomized controlled trial which compares the efficacy of an enhanced linkage to HIV care intervention vs. standard-of-care (paper-based referrals) at achieving individual and population-level HIV viral suppression, and intermediate outcomes of linkage to care, receipt of opportunistic infection prophylaxis, and antiretroviral therapy initiation following HBHCT. Approximately 600 men and women aged 18-59 who test HIV positive during district-wide HBHCT in rural Uganda will be enrolled in this study. Villages (clusters) are pair matched by population size and then randomly assigned to the intervention or standard-of-care arm. Study teams visit households and participants complete a baseline questionnaire, receive HIV counseling and testing, and have blood drawn for HIV viral load and CD4 testing. At baseline, standard-of-care arm participants receive referrals to HIV care including a paper-based referral and then receive their CD4 results via home visit 2 weeks later. Intervention arm participants receive an intervention counseling session at baseline, up to three follow-up counseling sessions at home, and a booster session at the HIV clinic if they present for care. These sessions each last approximately 30 min and consist of counseling to help clients: identify and reduce barriers to HIV care engagement, disclose their HIV status, identify a treatment supporter, and overcome HIV-related stigma through links to social support resources in the community. Participants in both arms complete interviewer-administered questionnaires at six and 12 months follow-up, HIV viral load and CD4 testing at 12 months follow-up, and allow access to their medical records.Discussion: The findings of this study can inform the integration of a potentially cost-effective approach to improving rates of linkage to care and HIV viral suppression in HBHCT. If effective, this intervention can improve treatment outcomes, reduce mortality, and through its effect on individual and population-level HIV viral load, and decrease HIV incidence.Trial Registration: NCT02545673. [ABSTRACT FROM AUTHOR]

Background: Studies measuring contact networks have helped to improve our understanding of infectious disease transmission. However, several methodological issues are still unresolved, such as which method of contact measurement is the most valid. Further, complete network analysis requires data from most, ideally all, members of a network and, to achieve this, acceptance of the measurement method. We aimed at investigating measurement error by comparing two methods of contact measurement - paper diaries vs. wearable proximity sensors - that were applied concurrently to the same population, and we measured acceptability.Methods: We investigated the contact network of one day of an epidemiology conference in September 2014. Seventy-six participants wore proximity sensors throughout the day while concurrently recording their contacts with other study participants in a paper-diary; they also reported on method acceptability.Results: There were 329 contact reports in the paper diaries, corresponding to 199 contacts, of which 130 were noted by both parties. The sensors recorded 316 contacts, which would have resulted in 632 contact reports if there had been perfect concordance in recording. We estimated the probabilities that a contact was reported in a diary as: P = 72 % for <5 min contact duration (significantly lower than the following, p < 0.05), P = 86 % for 5-15 min, P = 89 % for 15-60 min, and P = 94 % for >60 min. The sets of sensor-measured and self-reported contacts had a large intersection, but neither was a subset of the other. Participants' aggregated contact duration was mostly substantially longer in the diary data than in the sensor data. Twenty percent of respondents (>1 reported contact) stated that filling in the diary was too much work, 25 % of respondents reported difficulties in remembering contacts, and 93 % were comfortable having their conference contacts measured by sensors.Conclusion: Reporting and recording were not complete; reporting was particularly incomplete for contacts <5 min. The types of contact that both methods are capable of detecting are partly different. Participants appear to have overestimated the duration of their contacts. Conducting a study with diaries or wearable sensors was acceptable to and mostly easily done by participants. Both methods can be applied meaningfully if their specific limitations are considered and incompleteness is accounted for. [ABSTRACT FROM AUTHOR]

Background: Globally it is estimated that 480 000 people developed multidrug-resistant tuberculosis (MDR-TB) in 2014 and 190 000 people died from the disease. Successful treatment outcomes are achieved in only 50 % of patients with MDR-TB, compared to 86 % for drug susceptible disease. It is widely held that delay in time to initiation of treatment for MDR-TB is an important predictor of treatment outcome. The objective of this review was to assess the existing evidence on the outcomes of multidrug- and extensively drug-resistant tuberculosis patients treated early (≤4 weeks) versus late (>4 weeks) after diagnosis of drug resistance.Methods: Eight sources providing access to 17 globally representative electronic health care databases, indexes, sources of evidence-based reviews and grey literature were searched using terms incorporating time to treatment and MDR-TB. Two-stage sifting in duplicate was employed to assess studies against pre-specified inclusion and exclusion criteria. Only those articles reporting WHO-defined treatment outcomes were considered for inclusion. Articles reporting on fewer than 10 patients, published before 1990, or without a comparison of outcomes in patient groups experiencing different delays to treatment initiation were excluded.Results: The initial search yielded 1978 references, of which 1475 unique references remained after removal of duplicates and 28 articles published pre-1990. After title and abstract sifting, 64 papers underwent full text review. None of these articles fulfilled the criteria for inclusion in the review.Conclusions: Whilst there is an inherent logic in the theory that treatment delay will lead to poorer treatment outcomes, no published evidence was identified in this systematic review to support this hypothesis. Reports of programmatic changes leading to reductions in treatment delay exist in the literature, but attribution of differences in outcomes specifically to treatment delay is confounded by other contemporaneous changes. Further primary research on this question is not considered a high priority use of limited resources, though where data are available, improved reporting of outcomes by time to treatment should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Colonization with Staphylococcus aureus is a well-defined risk factor for disease in hospitals, which can range from minor skin infections to severe, systemic diseases. However, the generalizability of this finding has not been thoroughly investigated outside of the hospital environment. We aimed to assess the role of S. aureus colonization as a risk factor for disease in the community.Methods: We performed a meta-analysis of observational studies and searched PubMed for articles published between December 1979 and May 23, 2016. We included cohort, cross-sectional, and case-control studies that reported quantitative estimates of both S. aureus colonization and disease statuses of all study subjects. We excluded studies on recently hospitalized subjects, long-term care facilities, surgery patients, dialysis patients, hospital staff, S. aureus outbreaks, and livestock-associated infections. Our meta-analysis was performed using random-effects analysis to obtain pooled odds ratios (ORs) to compare the odds of S. aureus disease with respect to S. aureus colonization status.Results: We identified 3477 citations, of which 12 articles on 6998 subjects met the eligibility criteria. Overall, subjects colonized with S. aureus were more likely to progress to disease than those who were non-colonized: (OR 1.87, 95% CI 1.21-2.88, n = 7 studies). We observed a larger effect with methicillin-resistant S. aureus colonization (7.06, 4.60-10.84, n = 7 studies). However, the methicillin-sensitive S. aureus colonization was not associated with greater odds of disease (1.20, 0.69-2.06, n = 4 studies). Heterogeneity was present across studies in all of the subgroups: S. aureus (I2 = 95.0%, χ2 = 120.3, p < 0.001), MRSA (I2 = 92.8%, χ2 = 82.8, p = p < 0.001), and MSSA (I2 = 86.3%, χ2 = 21.8, p < 0.001).Conclusions: While the majority of papers individually support the assumption that colonization is a risk factor for S. aureus disease in the general population, there is marked heterogeneity between studies and further investigation is needed to identify the major sources of this variance. There is a shortage of literature addressing this topic in the community setting and a need for further research on colonization as a focus for disease prevention. [ABSTRACT FROM AUTHOR]

Background: Knowledge of HIV status can be important in reducing the risk of HIV exposure. In a European sample of men-who-have-sex-with-men (MSM), we aimed to identify factors associated with HIV serostatus disclosure to the most recent anal intercourse (AI) partner. We also aimed to describe the impact of HIV serostatus disclosure on HIV exposure risks.Methods: During 2013 and 2014, 4901 participants were recruited for the bio-behavioural Sialon-II study in 13 European cities. Behavioural data were collected with a self-administered paper questionnaire. Biological specimens were tested for HIV antibodies. Factors associated with HIV serostatus disclosure with the most recent AI partner were examined using bivariate and multilevel multivariate logistic regression analysis. We also describe the role of serostatus disclosure for HIV exposure of the most recent AI partner.Results: Thirty-five percent (n = 1450) of the study participants reported mutual serostatus disclosure with their most recent AI partner or disclosed having HIV to their partner. Most of these disclosures occurred between steady partners (74%, n = 1077). In addition to the type of partner and HIV diagnosis status, other factors positively associated with HIV serostatus disclosure in the multilevel multivariate logistic regression model were recent testing, no condom use, and outness regarding sexual orientation. Disclosure rates were lowest in three south-eastern European cities. Following condom use (51%, n = 2099), HIV serostatus disclosure (20%, n = 807) was the second most common prevention approach with the most recent AI partner, usually resulting in serosorting. A potential HIV exposure risk for the partner was reported by 26% (111/432) of HIV antibody positive study participants. In 18% (20/111) of exposure episodes, an incorrect HIV serostatus was unknowingly communicated. Partner exposures were equally distributed between steady and non-steady partners.Conclusions: The probability of HIV exposure through condomless AI is substantially lower after serostatus disclosure compared to non-disclosure. Incorrect knowledge of one's HIV status contributes to a large proportion of HIV exposures amongst European MSM. Maintaining or improving condom use for anal intercourse with non-steady partners, frequent testing to update HIV serostatus awareness, and increased serostatus disclosure particularly between steady partners are confirmed as key aspects for reducing HIV exposures amongst European MSM. [ABSTRACT FROM AUTHOR]

Background: Preventing respiratory tract infections (RTIs) could have profound effects on quality of life, primary care workload, antibiotic prescribing and stewardship. We aimed to identify factors that increase and decrease RTI acquisition within Organisation for Economic Cooperation and Development (OECD) member countries.Methods: Systematic search of Medline, Embase, Cochrane and ISI Web of Knowledge for studies conducted up to July 2020 reporting predisposing factors for community RTI acquisition. Pooled odds ratios were calculated using a random-effects model.Results: 23 studies investigated risk factors associated with community-acquired pneumonia (n = 15); any RTI (n = 4); influenza like illness (n = 2); and lower RTI (n = 2). Demographic, lifestyle and social factors were: underweight BMI (pooled odds ratio (ORp 2.14, 95% CI 1.58 to 2.70, p = 0.97); male sex (ORp 1.30, 95% CI 1.27 to 1.33, p = 0.66); contact with pets (ORp 1.35, 95% CI 1.16 to 1.54, p = 0.72); contact with children (ORp 1.35, 95% CI 1.15 to 1.56, p = 0.05); and ex-smoking status (ORp 1.57, 95% CI 1.26 to 1.88, p = 0.76). Health-related factors were: chronic liver condition (ORp 1.30, 95% CI 1.09 to 1.50, p = 0.34); chronic renal condition (ORp 1.47, 95% CI 1.09 to 1.85, p = 0.14); and any hospitalisation in previous five years (ORp 1.64, 95% CI 1.46 to 1.82, p = 0.66).Conclusions: We identified several modifiable risk factors associated with increased likelihood of acquiring RTIs in the community, including low BMI, contact with children and pets. Modification of risk factors and increased awareness of vulnerable groups could reduce morbidity, mortality and antibiotic use associated with RTIs.Prospero Registration: CRD42019134176. [ABSTRACT FROM AUTHOR]

Background: Little is known about the management of methicillin-resistant Staphylococcus aureus (MRSA) carriers in the German outpatient sector and about the impact of MRSA on their daily life. Reimbursement for MRSA related costs in the German outpatient sector is available since 2012, but its impact has not been studied yet. The aim of the study was to analyze the outpatient management of MRSA carriers from both, physicians' and MRSA carriers' perspective.Methods: Paper-based questionnaires were mailed to physicians providing outpatient care and to MRSA carriers in 2013. MRSA carriers were recruited among patients tested positive for MRSA during a hospital stay in 2012. General practitioners, specialists for internal medicine, urologists, and dermatologists working in the outpatient catchment areas of the hospitals were contacted.Results: Out of 910 MRSA carriers 16.5 % completed the questionnaires; among 851 physicians 9.5 % participated. 27.3 % of the responding MRSA carriers stated that no healthcare professional had ever talked to them about MRSA. 17.4 % reported self-stigmatization in terms of restricting social contacts; 47.3 % remembered decolonization and 33.3 % reported that their MRSA status was checked after discharge. Physicians displayed heterogeneous attitude and activity towards MRSA (number of applied decolonization and MRSA screenings). A minority (15.2 %) were satisfied with the reimbursement of costs, 35.9 % reported full agreement with the general recommendations for the handling of MRSA carriers.Conclusions: MRSA carriers appear not well informed; (self-) stigmatization is occurring and should be tackled. Greater awareness of MRSA as a problem in the outpatient sector could lead to a better handling of MRSA carriers. [ABSTRACT FROM AUTHOR]

Background: Nosocomial infections are the most common complication during inpatient hospital care. An increasing proportion of these infections are caused by multidrug-resistant organisms (MDROs). This report describes an intervention study which was designed to address the practical problems encountered in trying to avoid and treat infections caused by MDROs. The aim of the HARMONIC (Harmonized Approach to avert Multidrug-resistant Organisms and Nosocomial Infections) study is to provide comprehensive support to hospitals in a defined study area in north-east Germany, to meet statutory requirements. To this end, a multimodal system of hygiene management was implemented in the participating hospitals.Methods/design: HARMONIC is a controlled intervention study conducted in eight acute care hospitals in the 'Health Region Baltic Sea Coast' in Germany. The intervention measures include the provision of written recommendations on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) and multi-resistant Gram-negative bacteria (MRGN), supplemented by regional recommendations for antibiotic prescriptions. In addition, there is theoretical and practical training of health care workers (HCWs) in the prevention and handling of MDROs, as well as targeted and critically gauged applications of antibiotics. The main outcomes of the implementation and analysis of the HARMONIC study are: (i) screening rates for MRSA, VRE and MRGN in high-risk patients, (ii) the frequency of MRSA decolonization, (iii) the level of knowledge of HCWs concerning MDROs, and (iv) specific types and amounts of antibiotics used. The data are predominantly obtained by paper-based questionnaires and documentation sheets. A computer-assisted workflow-based documentation system was developed in order to provide support to the participating facilities. The investigation includes three nested studies on risk profiles of MDROs, health-related quality of life, and cost analysis. A six-month follow-up study investigates the quality of life after discharge, the long-term costs of the treatment of infections caused by MDROs, and the sustainability of MRSA eradication.Discussion: The aim of this study is to implement and evaluate an area-wide harmonized hygiene program to control the nosocomial spreading of MDROs. Comparability between the intervention and control group is ensured by matching the hospitals according to size (number of discharges per year/number of beds) and level of care (standard or maximum). The results of the study may provide important indications for the implementation of regional MDRO management programs. [ABSTRACT FROM AUTHOR]

Background: To combat emerging drug resistance in the Greater Mekong Sub-region (GMS) the World Health Organization and GMS countries have committed to eliminating malaria in the region by 2030. The overall approach includes providing universal access to diagnosis and treatment of malaria, and sustainable preventive measures, including vector control. Topical repellents are an intervention that can be used to target residual malaria transmission not covered by long lasting insecticide nets and indoor residual spraying. Although there is strong evidence that topical repellents protect against mosquito bites, evidence is not well established for the effectiveness of repellents distributed as part of malaria control activities in protecting against episodes of malaria. A common approach to deliver malaria services is to assign Village Health Volunteers (VHVs) to villages, particularly where limited or no services exist. The proposed trial aims to provide evidence for the effectiveness of repellent distributed through VHVs in reducing malaria.Methods: The study is an open stepped-wedge cluster-randomised controlled trial randomised at the village level. Using this approach, repellent (N,N-diethyl-benzamide - 12% w/w, cream) is distributed by VHVs in villages sequentially throughout the malaria transmission season. Villages will be grouped into blocks, with blocks transitioned monthly from control (no repellent) to intervention states (to receive repellent) across 14 monthly intervals in random order). This follows a 4-week baseline period where all villages do not receive repellent. The primary endpoint is defined as the number of individuals positive for Plasmodium falciparum and Plasmodium vivax infections diagnosed by a rapid diagnostic test. Secondary endpoints include symptomatic malaria, Polymerase Chain Reaction (PCR)-detectable Plasmodium spp. infections, molecular markers of drug resistance and antibodies specific for Plasmodium spp. parasites.Discussion: This study has been approved by relevant institutional ethics committees in Myanmar and Australia. Results will be disseminated through workshops, conferences and peer-reviewed publications. Findings will contribute to a better understanding of the optimal distribution mechanisms of repellent, context specific effectiveness and inform policy makers and implementers of malaria elimination programs in the GMS.Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12616001434482 ). Retrospectively registered 14th October 2016. [ABSTRACT FROM AUTHOR]

Background: People who inject drugs (PWID) are most at risk of hepatitis C virus infection in Australia. The introduction of transient elastography (TE) (measuring hepatitis fibrosis) and direct acting antiviral medications will likely alter the experience of living with hepatitis C. We aimed to explore positive and negative influences on wellbeing and stress among PWID with hepatitis C.Methods: The Treatment and Prevention (TAP) study examines the feasibility of treating hepatitis C mono-infected PWID in community settings. Semi-structured interviews were conducted with 16 purposively recruited TAP participants. Participants were aware of their hepatitis C seropositive status and had received fibrosis assessment (measured by TE) prior to interview. Questions were open-ended, focusing on the impact of health status on wellbeing and self-reported stress. Interviews were voice recorded, transcribed verbatim and thematically analysed, guided by Mishel's (1988) theory of Uncertainty in Illness.Results: In line with Mishel's theory of Uncertainty in Illness all participants reported hepatitis C-related uncertainty, particularly mis-information or a lack of knowledge surrounding liver health and the meaning of TE results. Those with greater fibrosis experienced an extra layer of prognostic uncertainty. Experiences of uncertainty were a key motivation to seek treatment, which was seen as a way to regain some stability in life. Treatment completion alleviated hepatitis C-related stress, and promoted feelings of empowerment and confidence in addressing other life challenges.Conclusion: TE scores seemingly provide some certainty. However, when paired with limited knowledge, particularly among people with severe fibrosis, TE may be a source of uncertainty and increased personal stress. This suggests the need for simple education programs and resources on liver health to minimise stress. [ABSTRACT FROM AUTHOR]

Background: To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or advanced presenters (CD4 count < 200/µL or AIDS event at enrolment).Methods: We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time.Results: Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status.Conclusions: A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities. [ABSTRACT FROM AUTHOR]

Background: People who inject drugs (PWID) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Treatment of PWID is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. New direct-acting antiviral medications are available for HCV with high cure rates and few side effects. The life expectancy and economic benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients. The purpose of this study is to evaluate the effectiveness of directly observed therapy and group treatment compared with self-administered individual treatment in a large, urban opioid agonist therapy clinic setting in the Bronx, New York.Methods/design: In this randomized controlled trial 150 PWID with chronic HCV were recruited from opioid agonist treatment (OAT) clinics and randomized to one of three models of onsite HCV treatment in OAT: 1) modified directly observed therapy; 2) group treatment; or 3) control - self-administered individual treatment. Participants were age 18 or older, HCV genotype 1, English or Spanish speaking, treatment naïve (or treatment experienced after 12/3/14), willing to receive HCV treatment onsite, receiving methadone or buprenorphine at the medication window at least once per week, and able to provide informed consent. Outcomes of interest include adherence (as measured by self-report and electronic blister packs), HCV treatment completion, sustained virologic response, drug resistance, and cost-effectiveness.Discussion: This paper describes the design and rationale of a randomized controlled trial comparing three models of care for HCV therapy delivered in an opioid agonist treatment program. Our trial will be critical to rigorously identify models of care that result in high adherence and cure rates. Use of blister pack technology will help us determine the role of adherence in successful cure of HCV. Moreover, the trial methodology outlined here can serve as a template for the development of future programs and studies among HCV-infected drug users receiving opioid agonist therapy, as well as the cost-effectiveness of such programs.Trial Registration: This trial was registered with ClinicalTrials.gov ( NCT01857245 ). Trial registration was obtained prospectively on May 20th, 2013. [ABSTRACT FROM AUTHOR]

Background: Many studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in Cameroon. There is paucity of data to support their continuous use in home-based treatment of uncomplicated Plasmodium falciparum malaria in Cameroon. Hence, this study aimed to assess the effectiveness and safety of AS-AQ versus AL for home-based treatment of uncomplicated P. falciparum malaria among children 6-120 months in Yaoundé, Cameroon.Methods: A two-arm, open-label, randomized, controlled trial comparing the equivalence of AS-AQ (experimental group) and AL (control group) was carried out from May 2019 to April 2020 at two secondary hospitals in Yaoundé. Participants were randomized to receive either AS-AQ or AL. After the first dose, antimalarial drugs were given at home, rather than under direct observation by a study staff. The conventional on-treatment and post-treatment laboratory and clinical evaluations were not done until day 3 of the full antimalarial treatment course. The evaluation of effectiveness was mainly based on per protocol polymerase chain reaction adjusted adequate clinical and parasitological response (PP PCR adjusted ACPR) on day 28 post-treatment. Safety was based on assessment of adverse events (AEs) and severe adverse events (SAEs) from day 1 to day 28.Results: A total of 242 children were randomized to receive AS-AQ (n = 114) and AL (n = 128). The PP PCR adjusted day 28 cure rates were [AS-AQ = 96.9% (95% CI, 91.2-99.4) versus AL = 95.5% (95% CI, 89.9-98.5), P = 0.797]. Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever.Conclusions: This study demonstrated that AS-AQ and AL are effective and safe for home management of malaria in Yaoundé. The evidence from this study supports the parallel use of the two drugs in routine practice. However, the findings from this study do not describe the likely duration of antimalarial effectiveness in holoendemic areas where multiple courses of treatment might be required.Trial Registration: This study is a randomized controlled trial and it was retrospectively registered on 23/09/2020 at ClinicalTrials.gov with registration number NCT04565184. [ABSTRACT FROM AUTHOR]

Background: In areas where Lyme disease is endemic, bites from ticks are common, but no vaccine is currently available against Lyme disease for humans. Therefore, the feasibility of using antibiotic prophylaxis to prevent Lyme disease after a tick bite is worth further exploration. Previous meta-analyses lack sufficient power to demonstrate the efficacy of about antibiotic prophylaxis for the prevention of Lyme disease following a tick bite. In this study, we explored more precise evidence and attempted to identify and update optimum treatment strategies.Methods: We searched PubMed, Embase, and the Cochrane Library for studies until March 23, 2021. We included studies if the enrolled patients were randomly allocated to a treatment or control group within 72 h following a tick bite and had no clinical evidence of Lyme disease at enrolment. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for data abstraction. Two authors (GZZ and XX) independently reviewed the abstracts and identified articles for detailed assessment. We used a random-effects model to calculate the pooled results and reported the 95% confidence interval (CI). Study quality was assessed using a modified Jadad scale, and publication bias was assessed using Egger's test. We calculated the risk ratio (RR) for the rates of unfavorable events in patients who received intervention versus the control group. This study is registered with PROSPERO, number CRD42021245002.Results: Six studies (3,766 individuals) were included. The pooled rate of unfavorable events in persons receiving treatment and the control group were 0.4% (95%CI: 0.1-1.1%) and 2.2% (95%CI: 1.6-3.0%), respectively. The pooled RR was 0.38 (95%CI: 0.22-0.66). Subgroup analysis revealed that the pooled RR was 0.29 (95%CI: 0.14-0.60) in the single-use 200-mg doxycycline group; 0.28 (95%CI: 0.05-1.67) in a 10-day course group (Amoxicillin, Penicillin or tetracycline); and 0.73 (95%CI: 0.25-2.08) in a topical antibiotic treatment group (Azithromycin).Conclusions: The available evidence supports the use of antibiotics for the prevention of Lyme disease, and reveals advantages of using single-dose; however, further confirmation is needed. [ABSTRACT FROM AUTHOR]

Background: Mobile text reminder (SMS) system is considered a viable strategy for targeting/facilitating healthy behavioural change including adherence to prescribed physical exercises (PE) and medication (antiretroviral therapy-ART) which should improve the quality of life (Qol) in people living with HIV/AIDS(PLWHA). Thus, the literature was appraised for evidence of SMS effectiveness in improving ART and PE adherence behaviours and QoL in PLWHA.Methods: Eight databases-AMED, CINAHL, Cochrane Library, EMBASE, EMCARE, Ovid MEDLINE, PsycINFO, and PubMed-were searched up to December 2020, using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol.This review included only randomised control trials (RCTs) investigating the effectiveness of SMS in improving QoL or PE or ART adherence behaviour or a combination of these variables in PLWHA >18 years. Two independent reviewers determined the eligibility of the studies. Data were extracted and the quality of the study was assessed with the Physiotherapy Evidence Database (PEDro) tool. The primary outcomes were ART and PE adherence behaviours while the secondary outcome was QoL.Result: A pooled estimate of effect was not calculated due to the heterogeneity of methods and outcome measures. Therefore, a narrative synthesis of ten studies that met the inclusion criteria (n = 1621 participants at study completion) comprising males/females, aged ≥ 18 years, was done. There was a significant improvement in ART adherence behaviour except in three underpowered studies. Only the SMS interventions that were developed using the Starks 3-steps Adherence model was associated with positive outcome. The only study that evaluated QoL was underpowered and reported no significant change while there were no RCTs on PE.Conclusion: Effects of SMS intervention trends towards a significant improvement in ART adherence behaviour in PLWHA. It is plausible that SMS reminders developed using the broader framework of the interpersonal health behaviour theory(ies) may have positive outcome. Nevertheless, the observed heterogeneity in the methods/outcome measures warrants a cautious interpretation of the findings. There is a lack/paucity of RCTs and therefore no evidence in support of the effectiveness of SMS intervention in improving PE adherence and QoL. Registration number NPLASY202060016. [ABSTRACT FROM AUTHOR]

Background: Prevalence data on viral hepatitis B (HBV), hepatitis C (HCV), and HIV infection in prison are often scarce or outdated. There is currently no systematic screening for these blood-borne viral infections (BBV) in Belgian prisons. There is an urgency to assess the prevalence of these BBV to inform policymakers and public healthcare.Methods: This was a multicentre, interventional study to assess the prevalence of BBV using opt-in screening in prisons across Belgium, April 2019 - March 2020. Prisoners were tested using a finger prick and BBV risk factors were assessed using a questionnaire. A generalized linear mixed model was used to investigate the association between the various risk factors and HCV.Results: In total, 886 prisoners from 11 Belgian prisons were screened. Study uptake ranged from 16.9 to 35.4% in long-term facilities. The prevalence of HCV antibodies (Ab), hepatitis B surface antigen (Ag) and HIV Ab/Ag was 5.0% (44/886), 0.8% (7/886), and 0.2% (2/886). The adjusted odds for HCV Ab were highest in prisoners who ever injected (p < 0.001; AOR 24.6 CI 95% (5.5-215.2). The prevalence of detectable HCV RNA in the total cohort was 2.1% (19/886). Thirteen (68.4%) prisoners were redirected for follow-up of their HCV infection.Conclusions: Opt-in testing for viral hepatitis B, C and HIV was relatively well-accepted in prisons. Compared with the general population, prisoners have a higher prevalence of infection with BBV, especially for HCV. Systematic screening for these BBV should be recommended in all prisons, preferably using opt-out to optimize screening uptake.Trial Registration: Retrospectively registered at clinical trials NCT04366492 April 29, 2020. [ABSTRACT FROM AUTHOR]

Background& Aims: There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.Methods: Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.Results: Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.Conclusions: TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.Trial Registration: This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019). [ABSTRACT FROM AUTHOR]

Background: The objectives of this review were to evaluate the vaccine effectiveness (VE) of the two-dose varicella vaccine for healthy children in China and explore the application of the approach of Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in observational studies on VE.Methods: We searched for observational studies on two-dose varicella VE for children in China aged 1-12 years that were published from 1997 to 2019, and assessed the quality of each study using the Newcastle Ottawa Scale (NOS). We used meta-analysis models to obtain the pooled two-dose VE, and the studies were divided into subgroups and analysed according to whether or not it was an outbreak investigation and its NOS score. The quality of evidence of VEs were rated by approach of the GRADE system.Results: A total of 12 studies and 87,196 individuals were included. The pooled two-dose VE was 90% (95% confidence interval [CI]: 69-97%). The VE of outbreak studies (87% [95% CI: 76-93%]) was lower than non-outbreak studies (99% [95% CI: 98-99%]). There was no significant difference in VEs by different NOS quality. The quality of the evidence assessment of pooled two-dose VE was "low", which was rated down by one category in limitations and publication bias respectively and rated up by two category in large effect. The quality of evidence assessment in subgroup of NOS score ≥ 7 was "moderate".Conclusions: The VE of two-dose varicella vaccine is relatively high in preventing varicella, and is recommended for countries which need further control for varicella. However, higher quality evidence is needed as a supplement for stronger recommendations. The approach of GRADE could be applied for rating the quality of evidence in observational study. [ABSTRACT FROM AUTHOR]

Background: Coronavirus Disease-2019 (COVID-19) pandemic has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation in Jiangsu province, China.Methods: Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected during follow-up. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation.Results: A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not belong to a cluster of cases in a family/community, etc.), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO2), and higher computer tomography (CT) image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03-1.09), lymphocyte count (109/L) (OR 0.25, 95%CI 0.08-0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15-1.51).Conclusions: Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19. [ABSTRACT FROM AUTHOR]

Background: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.Methods: Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7-10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.Results: The  South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24-1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.Conclusion: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.Trial Registration: This trial was registered on 17 October 2017 with the South African National Clinical Trial Register ( http://www.sanctr.gov.za/ ; BV-trial1; DOH-27-1117-5579 ). [ABSTRACT FROM AUTHOR]

Background: Scabies is an infectious disease that affects the skin caused by the mite Sarcoptes scabiei and it transmitted through close personal contact. Even though it is easily treatable disease, its prevalence is high and continuous as neglected tropical disease of resource-poor settings, and particularly affects young age groups. Despite of these facts, studies conducted in Ethiopia regarding to the prevalence and associated factors for scabies infestation have been highly variable and didn't well compiled. Due to that, the aim of this systematic review and meta-analysis was to estimates the overall prevalence of scabies and associated factors in all age groups in Ethiopia.Methods: International databases (PubMed/PMC/Midline, EMBASE, CINAHL, Web of Science, Google Scholar, Google and Science Direct) were systematically searched from December 1, 2019, to January 18, 2020. All observational studies noted the prevalence of human scabies and associated factors in Ethiopia were included. Two authors (AG and G.T) independently extracted all necessary data using a standardized data extraction format. The data which is extracted each study were analyzed using STATA Version 14.1. Heterogeneity among the included studies was assessed through the Cochrane Q test statistics and I2 test. Lastly, a random effects meta-analysis model was computed to fix overall prevalence and associated factors of scabies.Results: Twelve studies were included in this meta-analysis after 410 articles retrieved. Of these, eight studies were analyzed for prevalence estimation. The overall prevalence of scabies infestation was 14.5% (95%CI: 1.5, 27.6%) in Ethiopia. Furthermore, the subgroup analysis revealed the highest prevalence was 19.6% in Amhara region. A person from a large family size (OR: 3.1, 95% CI: 1.76, 5.67), and sharing a bed (OR: 3.59, 95%CI: 2.88, 4.47) were significantly associated with scabies.Conclusion: This study revealed the prevalence of scabies infestation was 14.5% in Ethiopia which was high. Persons from high family size and any contact with scabies case were factors associated with scabies. [ABSTRACT FROM AUTHOR]

Background: In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy.Methods: In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis.Results: Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4-96.4), 87.9% (95% CI 76.7-95), and 81.2% (95% CI 69.9-89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5-64.5), 8% (95% CI 2.2-19.2) and 16.7% (95% CI 8.3-28.5), while by Kato-Katz was 55.6% (95% CI 42.5-68.1), 8.6% (95% CI 2.9-19) and 11.6% (95% CI 5.1-21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3-4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7-92.1) and 12.9% (95% CI = 6.6-22) respectively.Conclusions: We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is a major global health problem. WHO guidelines recommend screening all people living with HIV for hepatitis C. Considering the limited resources for health in low and middle income countries, targeted HCV screening is potentially a more feasible screening strategy for many HIV cohorts. Hence there is an interest in developing clinician-friendly tools for selecting subgroups of HIV patients for whom HCV testing should be prioritized. Several statistical methods have been developed to predict a binary outcome. Multiple studies have compared the performance of different predictive models, but results were inconsistent.Methods: A cross-sectional HCV diagnostic study was conducted in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh, Cambodia. We compared the performance of logistic regression, Spiegelhalter-Knill-Jones and CART to predict Hepatitis C co-infection in this cohort. We estimated the number of HCV co-infections that would be missed. To correct for over-optimism, the leave-one-out bootstrap estimator was used for estimating this quantity.Results: Logistic regression misses the fewest HCV co-infections (8%), but would still refer 98% of HIV patients for HCV testing. Spiegelhalter-Knill-Jones (SKJ) and CART respectively miss 12% and 29% of HCV co-infections but would only refer about 30% for HCV testing.Conclusions: In our dataset, logistic regression has the highest log-likelihood and smallest proportions of HCV co-infections missed but Spiegelhalter-Knill-Jones has the highest area under the ROC curve. The likelihood ratios estimated by Spiegelhalter-Knill-Jones might be easier to interpret for clinicians than odds ratios estimated by logistic regression or the decision tree from CART. CART is the most flexible method, and no model has to be specified regarding presence of interactions and form of the relationship between outcome and predictor variables. [ABSTRACT FROM AUTHOR]

Background: Plague is a highly fatal disease caused by Yersinia pestis. Late diagnosis hampers disease outcome and effectiveness of control measures, induces death and disease spread. Advance on its diagnosis was the use of lateral flow rapid diagnostic test (RDT).Methods: We assessed the performance of the plague RDT based on Y. pestis F1 antigen detection more than 15 years after its deployment in Madagascar. We compared the RDT with bacteriological culture results, using data from plague notified cases collected during the periods for which both tests were performed independently and systematically.Results: Used with bubonic plague (BP) patient samples, RDTs had a sensitivity of 100% (95% CI: 99.7-100%), a specificity of 67% (95% CI: 64-70%) with a good agreement between bacteriology and RDT results (86%; κ = 0.70, 95% CI 0.67-0.73). For pneumonic plague (PP), RDT had a sensitivity of 100% (95% CI: 91-100%) and a specificity of 59% (95% CI: 49-68%) and concordance between the bacteriological and plague RDT results was moderate (70%; κ = 0.43, 95% CI 0.32-0.55). Analysis focusing on the 2017-2018 plague season including the unprecedented epidemic of PP showed that RDT used on BP samples still had a sensitivity of 100% (95% CI: 85-100%) and a specificity of 82% (95% CI: 48-98%) with a very good agreement with bacteriology 94% (κ = 0.86, 95% CI 0.67-1); for PP samples, concordance between the bacteriological and plague RDT results was poor (61%; κ = - 0.03, 95% CI -0.17 - 0.10).Conclusions: RDT performance appeared to be similar for the diagnosis of BP and PP except during the 2017 PP epidemic where RDT performance was low. This RDT, with its good sensitivity on both plague clinical forms during a normal plague season, remained a potential test for alert. Particularly for BP, it may be of great value in the decision process for the initiation of therapy. However, for PP, RDT may deliver false negative results due to inconsistent sample quality. Plague diagnosis could be improved through the development of next generation of RDTs. [ABSTRACT FROM AUTHOR]

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay.Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model.Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log10 copies/106 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4+ T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log10 copies/106 PBMCs.Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log10 copies/106 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART. [ABSTRACT FROM AUTHOR]

Background: Brucellosis is endemic in many areas in China. The current diagnosis of Brucellosis predominantly relies on the traditional bacterial culture and serum agglutination test. In this study, we aimed to explore the value of ELISA in the diagnosis of Brucellosis in Chinese population.Methods: We recruited 235 patients with a diagnosis of Brucellosis at different clinical stages: 117 in acute, 78 in subacute, and 40 in chronic. We also recruited 248 control patients who presented with similar clinical symptoms but with a different diagnosis other than Brucellosis. In addition, 90 healthy volunteers were also recruited. Bacterial culture, agglutination test and ELISA assay were performed to detect Brucella spp.Results: Among 235 patients with Brucellosis, 51 (21.7%) was positive for bacterial culture, 150 (63.8%) were positive by agglutination test, and 232 (98.7%) were positive by ELISA (IgG and/or IgM). When we stratified the patients based on the disease stages (acute, subacute and chronic), ELISA was the most sensitive method and showed a highest positive rate in all stages. By Receiver Operating Characteristic Curve analysis of ELISA results, we found that measurement of IgG level was superior to measurement of IgM level (AUC, 0.993 versus 0.877). Since the measurement of IgG itself missed rare cases in acute phase, we recommended measuring IgG and IgM simultaneously by ELISA for the diagnosis of Brucellosis. In term of the specificity of ELISA in the diagnosis of Brucellosis, our study showed that only 1.6% (4/248) non-Brucellosis patients were positive by ELISA; all positive cases were IgM only and none showed positive IgG. Similar results were found in healthy volunteers. In summary, our study concluded that ELISA is the most sensitive and specific method to detect Brucellosis in Chinese population.Conclusions: ELISA assay is sensitive, fast, and convenient to detect Brucellosis. It shows the high sensitivity and specifity and should be used as a routine lab test when Brucellosis is suspected in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The Xpert® MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA) is a cartridge-based nucleic acid amplification assay for rapidly diagnosing tuberculosis and assessing antibiotic sensitivity. Although previous evidence supports the use of Xpert for diagnosing extrapulmonary tuberculosis (EPTB) in adults, information regarding the accuracy of Xpert for EPTB only in children is lacking. This meta-analysis was performed to assess the accuracy of Xpert for detecting EPTB in children.Methods: We searched the MEDLINE, EMBASE, and Cochrane Infectious Diseases Group Specialized Register from January 1, 2010 to July 16, 2019 for studies of the diagnostic performance wherein Xpert was analyzed against cultures or composite reference standards for < 18-year-old children with EPTB.Results: In only pediatric studies, 8 studies including 652 samples were selected. The pooled sensitivity and specificity of Xpert for all samples were 71% (95% CI 0.63-0.79) and 97% (95% CI 0.95-0.99), respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.89. For lymph node tissues or aspirates, the pooled sensitivity and specificity of Xpert were 80% (95% CI 0.70-0.88) and 94% (95% CI 0.89-0.97), respectively; for cerebrospinal fluid (CSF), these values were 42% (95% CI 0.22-0.63) and 99% (95% CI 0.95-1.00), respectively.Conclusion: Overall, Xpert displayed high specificity but modest sensitivity across various samples for diagnosing pediatric EPTB compared to the composite reference standard. Xpert sensitivity varied with the sampling site and was especially lower in CSF samples. Positive Xpert results may be considered to indicate a presumptive case of pediatric EPTB, whereas negative test results indicate that the possibility of pediatric EPTB should not be excluded. [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method.Methods: We retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China).Results: Of the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9-72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0-75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0-94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002).Conclusions: Both cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method. [ABSTRACT FROM AUTHOR]

Background: For definitive diagnosis of cryptococcal meningitis, Cryptococcus neoformans and/or C. gattii must be identified within cerebral spinal fluid from the patients. The traditional methods for detecting Cryptococcus spp. such as India ink staining and culture are not ideal. Although sensitive and specific enough, detection of cryptococcal antigen polysaccharide has a high dose hook effect. Therefore, the aim of this study was to introduce a new rapid and simple detection method of Cryptococcus neoformans and C. gattii in cerebral spinal fluid.Methods: The lateral flow strips combined with recombinase polymerase amplification (LF-RPA) assay was constructed to detect the specific DNA sequences of C. neoformans and C. gattii. The detection limit was evaluated using serial dilutions of C. neoformans and C. gattii genomic DNA. The specificity was assessed by excessive amount of other pathogens genomic DNA. The optimal detection time and amplification temperature were also analyzed. The diagnostic parameters were first calculated using 114 clinical specimens and then compared with that of other diagnostic method. A brief analysis and comparison of different DNA extraction methods was discussed, too.Results: The LF-RPA assay could detect 0.64 pg of genomic DNA of C. neoformans per reaction within 10 min and was highly specific for Cryptococcus spp.. The system could work well at a wide range of temperature from 25 to 45 °C. The overall sensitivity and specificity were 95.2 and 95.8% respectively. As amplification template for LF-RPA assay, both cell lysates and genomic DNA produce similar experimental results.Conclusions: The LF-RPA system described here is shown to be a sensitive and specific method for the visible, rapid, and accurate detection of Cryptococcus spp. in cerebral spinal fluid and might be useful for clinical preliminary screening of cryptococcal meningitis. [ABSTRACT FROM AUTHOR]

Background: Large scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of infections in some areas and growing concerns of PZQ resistance have revealed the limitations of this strategy. Most studies assessing PZQ efficacy have used relatively insensitive parasitological diagnostics, such as the Kato-Katz (KK) and urine-filtration methods, thereby overestimating cure rates (CRs). This study aims to determine the efficacy of repeated PZQ treatments against Schistosoma mansoni infection in school-aged children in Côte d'Ivoire using the traditional KK technique, as well as more sensitive antigen- and DNA-detection methods.Methods: An open-label, randomised controlled trial will be conducted in school-aged children (5 to 18 years) from the region of Taabo, Côte d'Ivoire, an area endemic for S. mansoni. This 8-week trial includes four two-weekly standard doses of PZQ in the "intense treatment" intervention group and one standard dose of PZQ in the "standard treatment" control group. The efficacy of PZQ will be evaluated in stool samples using the KK technique and real-time PCR as well as in urine using the point-of-care circulating cathodic antigen test and the up-converting phosphor, lateral flow, circulating anodic antigen assay. The primary outcome of the study will be the difference in CR of intense versus standard treatment with PZQ on individuals with a confirmed S. mansoni infection measured by KK. Secondary outcomes include the difference in CR and intensity reduction rate between the intense and standard treatment groups as measured by the other diagnostic tests, as well as the accuracy of the different diagnostic tests, and the safety of PZQ.Discussion: This study will provide data on the efficacy of repeated PZQ treatment on the clearance of S. mansoni as measured by several diagnostic techniques. These findings will inform future mass drug administration policy and shed light on position of novel diagnostic tools to evaluate schistosomiasis control strategies.Trial Registration: The study is registered at EudraCT (2016-003017-10, date of registration: 22 July 2016) and ( NCT02868385 , date of registration: 16 August 2016). [ABSTRACT FROM AUTHOR]

Background: By 1990, 94 percent of the acquired immunodeficiency syndrome (AIDS) cases in Romania were in children less than 13 years of age. The majority of the cases were identified in the city of Constanta. The purpose of this paper was to describe the current burden of pediatric human immunodeficiency virus (HIV) infection in the Constanta county.Methods: A cross-sectional study was designed to address the primary objective. Between April 1999 and March 2000, all living cases of pediatric HIV infection in the Constanta county were identified from records at the HIV hospital clinic which serves the Constanta county. Standard demographic, social, clinical, treatment and hospitalization data were collected for each study subject. Data were analyzed according to cross-sectional study design methodology.Results: Of the 762 subjects, the majority were seven to 11 years of age, lived with their parents and attended school. Only 70% of the fathers and 13% of the mothers were employed. Horizontal transmission accounted for 90% of the cases. Most of the children had moderate to severe disease as indicated by their AIDS-defining signs; 40% had AIDS. Less than half of the children were receiving antiretroviral therapy (ART). ART and children of mothers with a high school or greater education were independent predictors of long-term non-progression of HIV disease.Conclusions: This cross-sectional study demonstrated that ten years after the HIV epidemic was identified in Romania, it remains a health and economic burden. The infected children are very ill, but ART is not available for all. The proportion with vertical transmission has increased from an estimated four % to nine %. Our findings support the need to get HIV therapy to economically challenged countries such as Romania. [ABSTRACT FROM AUTHOR]

Background: Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure.Methods: Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012.Results: Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%.Conclusions: This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications. [ABSTRACT FROM AUTHOR]

Background: Implant-related infections, including those of peri-prosthetic joint (PJIs), osteosynthesis and other biomaterials, are biofilm-related. Pathogen identification is considered the diagnostic benchmark; however, the presence of bacterial biofilms makes pathogen detection with traditional microbiological techniques only partially effective. To improve microbiological diagnostic accuracy, some biofilm debonding techniques have been recently proposed. Aim of this health economics assessment study was to evaluate their economic impact on hospital costs.Methods: Direct and indirect hospital costs connected with the routine introduction of sonication and dithiothreitol treatment applied to hip and knee PJIs and of tissue cultures were examined. In particular the consequences of diagnostic inaccuracy, the opportunities, costs, and risks of each technique were calculated.Results: Considering an average of five samples per patient, processed separately with traditional tissue culture with or without sonication of prosthetic components, or pooled together using the MicroDTTect device (a close system for sample collection, transport and treatment with Dithiothreitol for microbial release from biofilm), the overall mean direct cost per patient was € 397 and € 393 for sonication or MicroDTTect, respectively, compared to € 308 for traditional tissue cultures. In terms of opportunity costs, MicroDTTect was the most effective technique, allowing for a 35% or 55% reduction in time required for sample treatment, compared to tissue cultures combined or not with sonication, respectively. Pooling together direct and indirect costs associated with false positive and negative results of the different diagnostic techniques, unnecessary medical treatments and possible medical claims, MicroDTTect or sonication become increasingly cost-effective when the extra-costs, generated by diagnostic inaccuracy of traditional tissue culture, took place, respectively, in 2% or 20% or more of the patients.Conclusions: This is the first study specifically focused on the economic impact of the routine clinical use of microbiological antibiofilm sampling and processing techniques in orthopaedics. Although our results may suffer from a potential country and hospital bias, as the data collection process for direct and indirect costs is specific to each institution and country, this analysis highlights the potential economic advantage to hospitals associated with the routine introduction of antibiofilm techniques for microbiological diagnosis of PJI. [ABSTRACT FROM AUTHOR]

Background: S.aureus is a predominant pathogen that causes infection in critically ill patients, but little information exists regarding the characterization of S. aureus from different sources in burn patients in southeastern China.Methods: We enrolled 125 patients with S. aureus infection in burns center between Jan 2014 and Dec 2015. S. aureus isolates were characterized by antimicrobial susceptibility test, toxin gene detection, and molecular typing with multilocus sequence type, staphylococcal protein A (spa) type, and staphylococcal cassette chromosome mec (SCCmec) type.Results: Sixty-eight MRSA were isolated from SSTI and 31 from non-SSTI patients, respectively. Overall, the drug-resistant ability of S. aureus isolated from SSTI was higher than that from non-SSTI groups. SCCmecIII-CC239-t030 was the most common clone (38 from SSTIs, and 8 from non-SSTIs). Seg was the most common enterotoxin gene (21 from SSTIs and 33 from non-SSTIs). Isolates from SSTIs was more likely to carry seb (P = 0.04), while those from non-SSTIs tended to carry sea and seg (P = 0.002 and 0.01, respectively). Although isolates carried four hemolysin genes, there was no significant difference between them (P > 0.05).Conclusion: SCCmecIII-CC239-t030 was the most common clone in Jiangxi burns center, China. The molecular characterization of S. aureus was quite different between SSTI and non-SSTI groups. [ABSTRACT FROM AUTHOR]

Background: Zika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in urine and in semen. ZIKV infection can have dramatic consequences such as microcephaly and Guillain-Barré syndrome. ZIKV sexual transmission has been documented. A better understanding of ZIKV presence and persistence across biologic compartments is needed to devise rational measures to prevent its transmission.Methods: This observational cohort study will recruit non-pregnant participants aged 18 years and above with confirmed ZIKV infection [positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men and women in ZIKV infection acute phase, and their symptomatic or asymptomatic household/sexual infected contacts. Specimens of blood, urine, semen, vaginal secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and breast milk (if applicable) will be collected at pre-established intervals and tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya, HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M and G), plaque reduction neutralization test (if simultaneously positive for ZIKV and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic characteristics and comorbidities will be collected in parallel. Participants will be followed up for 12 months.Discussion: This prolonged longitudinal follow-up of ZIKV infected persons with regular biologic testing and data collection will offer a unique opportunity to investigate the presence and persistence of ZIKV in various biologic compartments, their clinical and immunological correlates as well as the possibility of ZIKV reactivation/reinfection over time. This valuable information will substantially contribute to the body of knowledge on ZIKV infection and serve as a base for the development of more effective recommendation on the prevention of ZIKV transmission.Trial Registration: NCT03106714 . Registration Date: April, 7, 2017. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a neglected mycobacterial skin infection caused by Mycobacterium ulcerans. This disease mostly affects poor rural populations, especially in areas with low hygiene standards and sanitation coverage. The objective of this study was to identify these risk factors in the districts of Zio and Yoto of the Maritime Region in Togo.Methods: We conducted a case-control study in Zio and Yoto, two districts proved BU endemic from November 2014 to May 2015. BU cases were diagnosed according to the WHO clinical case definition at the Centre Hospitalier Régional de Tsévié (CHR Tsévié) and confirmed by Ziehl-Neelsen (ZN) microscopy and IS2404 polymerase chain reaction (PCR). For each case, up to two controls matched by sex and place of residence were recruited. Socio-demographic, environmental or behavioral data were collected and conditional logistic regression analysis was used to identify and compare risk factors between BU cases and controls.Results: A total of 83 cases and 128 controls were enrolled. The median age was 15 years (range 3-65 years). Multivariate conditional logistic regression analysis after adjustment for potential confounders identified age (< 10 years (OR =11.48, 95% CI = 3.72-35.43) and 10-14 years (OR = 3.63, 95% CI = 1.22-10.83)), receiving insect bites near a river (OR = 7.8, 95% CI = 1.48-41.21) and bathing with water from open borehole (OR = 5.77, (1.11-29.27)) as independent predictors of acquiring BU infection.Conclusions: This study identified age, bathing with water from open borehole and receiving insect bites near a river as potential risk of acquiring BU infection in Zio and Yoto districts of the Maritime Region in south Togo. [ABSTRACT FROM AUTHOR]

Background: Genital warts are one of the most common forms of sexually-transmitted disease, but their epidemiology has yet to be thoroughly elucidated. The present study was designed to shed light on the prevalence of clinically-confirmed, self-reported genital warts (GWs) in a representative sample of the university population.Methods: In 2015, a cross-sectional survey was conducted on 11,096 individuals approached at the Students Information Bureau where they came to enroll for a university degree course. Participants completed an anonymous, self-administered questionnaire providing information on their sociodemographic characteristics, sexual behavior, and any history of clinically-diagnosed genital warts. Multivariate logistic regression was then used to identify any factors associated with the disease.Results: Our analysis was conducted on 9259 questionnaires (83.4%). Participants were a mean 21.8 ± 4.8 years of age, and 59.6% were female. Overall, 124 individuals (1.3%, 95%CI: 1.0-1.6) reported having been diagnosed with genital warts: 48 men (1.3%, 95%CI: 0.9-1.6), and 76 women (1.4% 95%CI: 1.1-1.7). Overall, 22.5% of the sample were vaccinated (1.3% of the males and 36.8% of the females). The group of respondents aged 30 years or more had the highest incidence of genital warts (males: 5.6%, 95%CI: 2.5-8.6; females: 6.9%, 95%CI: 3.4-10.4). The independent risk factors associated with a history of disease were (for both genders) a history of other sexually-transmitted diseases, and ≥2 sex partners in the previous 24 months. A protective role emerged for routine condom use. Additional risk factors associated with genital warts in males concerned men who have sex with men, bisexuality vis-à-vis heterosexuality, and smoking.Conclusions: The findings emerging from our study help to further clarify the epidemiology of genital warts in young people, and may be useful to public health decision-makers. This study showed that genital warts occur in men as well as women, and suggests that both genders should be monitored for this disease to ascertain the effects of the free HPV vaccination offered to all girls in the Veneto in their 12th year of life since 2008, and to all boys of the same age since 2015. [ABSTRACT FROM AUTHOR]

Background: Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence.Methods: Migrant country of birth and population size extracted from statistical databases and anti-HCV prevalence in countries of birth and in EU/EEA countries derived from a systematic literature search were used to estimate caseload among and most affected migrants. Reliability of country of birth prevalence as a proxy for migrant prevalence was assessed via a systematic literature search.Results: Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom were born in endemic (anti-HCV prevalence ≥1%) countries. Anti-HCV/CHC prevalence in migrants from endemic countries residing in the EU/EEA is estimated at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease burden in the EU/EEA. The highest number of cases is found among migrants from Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco, Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting prevalence in migrants in Europe were identified; in seven of these estimates, prevalence was comparable with the country of birth prevalence and in three estimates it was lower.Discussion: Migrants are disproportionately affected by CHC, account for a considerable number of CHC infections in EU/EEA countries, and are an important population for targeted case finding and treatment. Limited data suggest that country of birth prevalence can be used as a proxy for the prevalence in migrants. [ABSTRACT FROM AUTHOR]

Background: School closure is often considered as an option to mitigate influenza epidemics because of its potential to reduce transmission in children and then in the community. The policy is still however highly debated because of controversial evidence. Moreover, the specific mechanisms leading to mitigation are not clearly identified.Methods: We introduced a stochastic spatial age-specific metapopulation model to assess the role of holiday-associated behavioral changes and how they affect seasonal influenza dynamics. The model is applied to Belgium, parameterized with country-specific data on social mixing and travel, and calibrated to the 2008/2009 influenza season. It includes behavioral changes occurring during weekend vs. weekday, and holiday vs. school-term. Several experimental scenarios are explored to identify the relevant social and behavioral mechanisms.Results: Stochastic numerical simulations show that holidays considerably delay the peak of the season and mitigate its impact. Changes in mixing patterns are responsible for the observed effects, whereas changes in travel behavior do not alter the epidemic. Weekends are important in slowing down the season by periodically dampening transmission. Christmas holidays have the largest impact on the epidemic, however later school breaks may help in reducing the epidemic size, stressing the importance of considering the full calendar. An extension of the Christmas holiday of 1 week may further mitigate the epidemic.Conclusion: Changes in the way individuals establish contacts during holidays are the key ingredient explaining the mitigating effect of regular school closure. Our findings highlight the need to quantify these changes in different demographic and epidemic contexts in order to provide accurate and reliable evaluations of closure effectiveness. They also suggest strategic policies in the distribution of holiday periods to minimize the epidemic impact. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) related morbidity and mortality can be reduced through risk group screening, linkage to care and anti-viral treatment. This study estimates the number of CHB cases among foreign-born (migrants) in the European Union and European Economic Area (EU/EEA) countries in order to identify the most affected migrant populations. Methods: The CHB burden was estimated by combining: demographic data on migrant population size by country of birth in the EU/EEA, extracted from European statistical databases; and CHB prevalence in migrants' countries of birth and in EU/EEA countries, derived from a systematic literature search. The relative contribution of migrants from endemic countries to the total CHB burden in each country was also estimated. The reliability of using country of birth prevalence as a proxy for prevalence among migrants was assessed by comparing it to the prevalence found in studies among migrants in Europe. Results: An estimated 1-1.9 million CHB-infected migrants from endemic countries (prevalence ≥2%) reside in the EU/ EEA. Migrants from endemic countries comprise 10.3% of the total EU/EEA population but account for 25% (15%-35%) of all CHB cases. Migrants born in China and Romania contribute the largest number of infections, with over 100,000 estimated CHB cases each, followed by migrants from Turkey, Albania and Russia, in descending order, with over 50,000 estimated CHB cases each. The CHB prevalence reported in studies among migrants in EU/EEA countries was lower than the country of birth prevalence in 9 of 14 studies. Conclusions: Migrants from endemic countries are disproportionately affected by CHB; their contribution however varies between EU/EEA countries. Migrant focused screening strategies would be most effective in countries with a high relative contribution of migrants and a low general population prevalence. In countries with a higher general population prevalence and a lower relative contribution of migrants, screening specific birth cohorts may be a more effective use of scarce resources. Quantifying the number of CHB infections among 50 different migrant groups residing in each of the 31 EU/EEA host countries helps to identify the most affected migrant communities who would benefit from targeted screening and linkage to care. [ABSTRACT FROM AUTHOR]

Background: Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the human innate immune system and the polymorphisms in TLRs may alter their function. The present study aimed to investigate the association between TLR polymorphisms and disease progression of chronic HBV infection.Methods: During the study period, 211 treatment-naïve patients with chronic HBV infection were recruited, and blood samples were collected from each individual. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was employed to genotype the selected TLR polymorphisms after human genome extraction. In addition, HbsAg, TNF-α, and IL-6 levels were quantified using enzyme linked immunosorbent assay (ELISA). Statistical analyses were conducted to investigate the association between TLR polymorphisms and hepatitis activity, liver function parameters, HbsAg level, and cytokine level.Results: We did not observe any mutations in rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic regression revealed that mutations in rs3804099 and rs4696480 were associated with milder hepatitis activity. Consistent with the logistic regression, improved liver function parameters and reduced level of both HbsAg and cytokines were also correlated with the mutant carriers of rs3804099 and rs4696480.Conclusions: TLR mutations were significantly associated with milder hepatitis activity among patients with chronic HBV infection. Therefore, we conclude that the activation of TLR pathways may further intensify the inflammation of hepatocytes, and leads to progression of disease. [ABSTRACT FROM AUTHOR]

Background: In April 2015, Kamwenge District, western Uganda reported a measles outbreak. We investigated the outbreak to identify potential exposures that facilitated measles transmission, assess vaccine effectiveness (VE) and vaccination coverage (VC), and recommend prevention and control measures.Methods: For this investigation, a probable case was defined as onset of fever and generalized maculopapular rash, plus ≥1 of the following symptoms: Coryza, conjunctivitis, or cough. A confirmed case was defined as a probable case plus identification of measles-specific IgM in serum. For case-finding, we reviewed patients' medical records and conducted in-home patient examination. In a case-control study, we compared exposures of case-patients and controls matched by age and village of residence. For children aged 9 m-5y, we estimated VC using the percent of children among the controls who had been vaccinated against measles, and calculated VE using the formula, VE = 1 - ORM-H, where ORM-H was the Mantel-Haenszel odds ratio associated with having a measles vaccination history.Results: We identified 213 probable cases with onset between April and August, 2015. Of 23 blood specimens collected, 78% were positive for measles-specific IgM. Measles attack rate was highest in the youngest age-group, 0-5y (13/10,000), and decreased as age increased. The epidemic curve indicated sustained propagation in the community. Of the 50 case-patients and 200 controls, 42% of case-patients and 12% of controls visited health centers during their likely exposure period (ORM-H = 6.1; 95% CI = 2.7-14). Among children aged 9 m-5y, VE was estimated at 70% (95% CI: 24-88%), and VC at 75% (95% CI: 67-83%). Excessive crowding was observed at all health centers; no patient triage-system existed.Conclusions: The spread of measles during this outbreak was facilitated by patient mixing at crowded health centers, suboptimal VE and inadequate VC. We recommended emergency immunization campaign targeting children <5y in the affected sub-counties, as well as triaging and isolation of febrile or rash patients visiting health centers. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB. The T-cell response to a group of so-called latency (DosR-regulon-encoded) and Resuscitation Promoting (Rpf) antigens of Mtb has been proved to be significantly higher in LTBI compared to active TB across many populations, suggesting their potential use as biomarkers to differentiate latent from active TB.Methods: PBMCs from a group LTBI (n = 20) and pulmonary TB patients (PTB, n = 21) from an endemic community for TB of the city of Medellín, Colombia, were in vitro stimulated for 7 days with DosR- (Rv1737c, Rv2029c, and Rv2628), Rpf- (Rv0867c and Rv2389c), the recombinant fusion protein ESAT-6-CFP10 (E6-C10)-, or PPD-antigen. The induced IFNγ levels detectable in the supernatants of the antigen-stimulated cells were then used to calculate specificity and sensitivity in discriminating LTBI from PTB, using different statistical approaches.Results: IFNγ production in response to DosR and Rpf antigens was significantly higher in LTBI compared to PTB. ROC curve analyses of IFNγ production allowed differentiation of LTBI from PTB with areas under the curve higher than 0.70. Furthermore, Multiple Correspondence Analysis (MCA) revealed that LTBI is associated with higher levels of IFNγ in response to the different antigens compared to PTB. Analysis based on decision trees showed that the IFNγ levels produced in response to Rv2029c was the leading variable that best-classified disease status. Finally, logistic regression analysis predicted that IFNγ produced by PBMCs in response to E6-C10, Rv2029c, Rv0867c (RpfA) and Rv2389c (RpfA) antigens correlates best with the probability of being latently infected.Conclusions: The Mtb antigens E6-C10, Rv2029c (PfkB), Rv0867c (RpfA) and Rv2389c (RpfA), may be potential candidates to discriminate LTBI from PTB. [ABSTRACT FROM AUTHOR]

Background: Opportunistic infections due to Candida species occur frequently in cancer patients because of their inherent immunosuppression. The aim of the present study was to investigate the epidemiology of yeast species from the oral cavity of patients during treatment for oncological and haematological malignancies.Methods: MALDI-TOF was performed to identify yeasts isolated from the oral cavity of 350 cancer patients. Moreover, antifungal susceptibility testing was performed in according to CLSI guidelines (M27-A3).Results: Among 162 yeasts and yeast-like fungi isolated from the oral cavity of cancer patients, Candida albicans was the most common species (50.6%), followed by Candida glabrata (24.7%), Pichia kudriavzevii (Candida krusei (9.9%)), Candida tropicalis (4.3%), Candida dubliniensis (3.7%), Kluyveromyces marxianus (Candida kefyr (3.7%)) and Candida parapsilosis (1%). In addition, uncommon yeast species i.e., Saprochaete capitata, Saccharomyces cerevisiae, Clavispora lusitaniae (C. lusitaniae) and Pichia kluyveri (C. eremophila) were recovered from oral lesions. Oral colonization by C. albicans, non-albicans Candida species and uncommon yeasts were as follow; 55%, 44% and 1%, whereas oral infection due to C. albicans was 33.3%, non-albicans Candida species 60.6%, and uncommon yeasts 6.1%. Poor oral hygiene and xerostomia were identified as independent risk factors associated with oral yeast colonization. The overall resistance to fluconazole was 11.7% (19/162). Low MIC values were observed for anidulafungin for all Candida and uncommon yeast species.Conclusions: This current study provides insight into the prevalence and susceptibility profiles of Candida species, including emerging Candida species and uncommon yeasts, isolated from the oral cavity of Iranian cancer patients. The incidence of oral candidiasis was higher amongst patients with hematological malignancies. The majority of oral infections were caused by non-albicans Candida species which were often more resistant to anti-fungal agents. Our findings suggest that anidulafungin should be used as antifungal of choice for prophylaxis in clinically high-risk patients with documented oral colonization or infection. [ABSTRACT FROM AUTHOR]

Background: To determine the linear and non-linear interacting relationships between weather factors and hand, foot and mouth disease (HFMD) in children in Gansu, China, and gain further traction as an early warning signal based on weather variability for HFMD transmission.Method: Weekly HFMD cases aged less than 15 and meteorological information from 2010 to 2014 in Jiuquan, Lanzhou and Tianshu, Gansu, China were collected. Generalized linear regression models (GLM) with Poisson link and classification and regression trees (CART) were employed to determine the combined and interactive relationship of weather factors and HFMD in both linear and non-linear ways.Results: GLM suggested an increase in weekly HFMD of 5.9% [95% confidence interval (CI): 5.4%, 6.5%] in Tianshui, 2.8% [2.5%, 3.1%] in Lanzhou and 1.8% [1.4%, 2.2%] in Jiuquan in association with a 1 °C increase in average temperature, respectively. And 1% increase of relative humidity could increase weekly HFMD of 2.47% [2.23%, 2.71%] in Lanzhou and 1.11% [0.72%, 1.51%] in Tianshui. CART revealed that average temperature and relative humidity were the first two important determinants, and their threshold values for average temperature deceased from 20 °C of Jiuquan to 16 °C in Tianshui; and for relative humidity, threshold values increased from 38% of Jiuquan to 65% of Tianshui.Conclusion: Average temperature was the primary weather factor in three areas, more sensitive in southeast Tianshui, compared with northwest Jiuquan; Relative humidity's effect on HFMD showed a non-linear interacting relationship with average temperature. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) infections are an important cause of childhood morbidity and mortality. The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia.Methods: We did a one year prospective study of children hospitalised with suspected CNS infection at Angkor Hospital for Children, Siem Reap. Cerebrospinal fluid specimens (CSF) samples underwent culture, multiplex PCR and serological analysis to identify a range of bacterial and viral pathogens. Viral metagenomics was performed on a subset of pathogen negative specimens.Results: Between 1st October 2014 and 30th September 2015, 284 analysable patients were enrolled. The median patient age was 2.6 years; 62.0% were aged <5 years. CSF white blood cell count was ≥10 cells/μL in 116/272 (42.6%) cases. CNS infection was microbiologically confirmed in 55 children (19.3%). Enteroviruses (21/55), Japanese encephalitis virus (17/55), and Streptococcus pneumoniae (7/55) accounted for 45 (81.8%) of all pathogens identified. Of the pathogens detected, 74.5% (41/55) were viruses and 23.6% (13/55) were bacteria. The majority of patients were treated with ceftriaxone empirically. The case fatality rate was 2.5%.Conclusions: Enteroviruses, JEV and S. pneumoniae are the most frequently detected causes of CNS infection in hospitalised Cambodian children. [ABSTRACT FROM AUTHOR]

Background: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains.Methods: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100.Results: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1).Conclusions: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making.Trial Registration: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012. [ABSTRACT FROM AUTHOR]