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Current guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children.
The CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population ‘bounce-back’ if deworming is ceased due to low STH prevalence.
The first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs.
Carla Bellomo, Daniel Alonso, Rocío Coelho, Ayelén Iglesias, Natalia Periolo, Valeria P. Martinez
Hantavirus Pulmonary Syndrome (HPS) was described in Argentina in 1995 when Andes virus (ANDV) was firstly characterized. HPS is a zoonotic disease transmitted to humans mainly from rodent reservoirs; however, person-to-person transmission has been well documented for ANDV. HPS is characterized by severe noncardiogenic pulmonary edema resulting in respiratory compromise, with a case-fatality higher than 30%. The aim of the present study was to describe the first newborn case infected with ANDV and to assess possible routes of viral transmission including novel possibilities: intrauterine, perinatal, and breastfeeding infections.
Ssempijja V, Nason M, Nakigozi G, et al.
AbstractIntroductionAfter scaleup of antiretroviral therapy (ART), routine annual viral load monitoring has been adopted by most countries, but reduced frequency of viral load monitoring may offer cost savings in resource limited settings. We investigated if viral load monitoring frequency could be reduced while maintaining detection of treatment failure.MethodsThe Rakai Health Sciences Program performed routine, biannual viral load monitoring on 2,489 HIV infected persons (age 15+). Based on these data, we built a two-stage simulation model to compare different viral load monitoring schemes. We fit Weibull regression models for time to viral load above 1000 copies/ml (treatment failure), and simulated data for 10,000 individuals over 5 years to compare five monitoring schemes to the current viral load testing every six months and testing every 12 months.ResultsAmong seven monitoring schemes tested, monitoring every six months for all subjects had the fewest months of undetected failure but also had the highest number of viral load tests. Adaptive schemes using previous viral load measurements to inform future monitoring significantly decreased the number of viral load tests without markedly increasing the number of months of undetected failure. The best adaptive monitoring scheme resulted in a 67% reduction in viral load measurements, while increasing the months of undetected failure by
To reduce acquisition and relapse of bacterial vaginosis (BV), lactobacilli must be maintained in the vaginal microbiome. Probiotic lactobacilli may aid this purpose. We investigated whether vaginal probiotics (containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869) would result in vaginal colonisation with lactobacilli in women with and without BV.
This prospective, partially randomised, exploratory pilot study was conducted in Soweto, South Africa. Thirty-nine sexually-active, HIV negative women were enrolled from October 2014 to May 2016 into three arms. Women who did not have BV (Group 1, n = 13) self-administered probiotic capsules vaginally once daily for 30 days, then once a week until Day 190. Women diagnosed with BV were randomized into Group 2 (n = 12) or Group 3 (n = 14) and treated with the triple oral antibiotic combination for vaginal discharge syndrome per South African guidelines (cefixime 400 mg stat, doxycycline 100 mg BD for 7 days and metronidazole 2 g stat). Immediately after antibiotic treatment, women in Group 2 self-administered probiotic capsules vaginally once daily for 30 days then vaginally once a week until Day 190. Women in Group 3 were not given lactobacilli.
During the study, L. rhamnosus DSM 14870 or L. gasseri DSM 14869, were isolated in 5/13 (38.5%) women in Group 1 compared to 10/12 (83.3%) women in Group 2 (p = 0.041). The 1-month and 6-month BV cure rates were similar (P > 0.05) between Group 2 (42 and 25%) compared to Group 3 (36 and 25%). In Group 2, no correlation was observed between the frequency of isolation of the two Lactobacillus strains and the 1-month or 6-month cure rate.
Supplementation with vaginal probiotic capsules resulted in colonisation of the vagina by the Lactobacillus strains (L. rhamnosus DSM 14870 and L. gasseri DSM 14869) contained in the capsules. We observed low initial cure rates of BV after a stat dose of metronidazole and that the probiotic did not improve BV cure rates or alleviate recurrence which could be due to treatment failure or very limited power of the study.
Registered at the Pan African Clinical Trial Registry (www.pactr.org) on April 13, 2018 (retrospectively registered). Trial identification number: PACTR201804003327269.
Barner A, Bruno-Murtha L.
Webb B, Majers J, Healy R, et al.
AbstractBackgroundAntibiotic stewardship is challenging in hematological malignancy patients.MethodsQuasi-experimental implementation study of two antimicrobial stewardship interventions in a hematological malignancy unit: 1) monthly antibiotic cycling for febrile neutropenia: cefepime (+/- metronidazole) and piperacillin-tazobactam and 2) a clinical prediction rule to guide anti-VRE therapy. We used interrupted time-series analysis (ITS) to compare antibiotic use and logistic regression to adjust observed unit-level changes in resistant infections by background community rates.Results2434 admissions spanning 3 years prior and 2 years post-implementation were included. Unadjusted carbapenem and daptomycin use decreased significantly. In ITS analysis, carbapenem use decreased by -230 DOT/1000 patient days (95% confidence interval (CI) -290 to -180), p
The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs.
We conducted a cross sectional study in all HIV- infected patients attending the HIV clinic in the Centre hospitalier universitaire de Montréal (CHUM) with DEXA scan. Lipodystrophy was defined as a trunk/limb fat ratio ≥ 1.5. Association between cumulative exposure to antiretroviral (measured in years of use) with trunk/limb fat ratio (coded as a continuous variable) was assessed using univariate and multivariate linear regression for each antiretroviral drug with at least 40 exposed patients.
One hundred sixty-six patients were included. Seventy-five percent were male, median age was 56 years, 67% were Caucasian. Overall, prevalence of lipodystrophy was 47%, with a mean trunk/limb fat ratio of 1.87, SD = 1.03, min = 0.6 and max = 5.87. Each 10-year increase in age and HIV infection duration was associated with an average increase of 0.24 and 0.34 for the trunk/limb fat ratio respectively. (p = 0.003, p = 0.002, respectively) Patients classified as lipodystrophic were more likely to be diabetic (50 vs. 28%, p = 0.07) and to have dyslipidemia (47 vs. 19%, p = 0.01). According to viral load at DEXA test, each one log increase was associated with less probability (0.7) of lipodystrophy. (p = 0.01) Among ARV drugs tested, there was an association between years of use of d4T, ritonavir and raltegravir and higher trunk/limb fat ratio (indicating more lipodystrophy) (p
The association between Toxoplasma gondii infection and thyroid disease has been poorly studied. Therefore, we sought to determine the association between T. gondii seropositivity and thyroid dysfunction.
We performed an age- and gender-matched case-control study of 176 patients suffering from hypothyroidism (n = 161) or hyperthyroidism (n = 15) and 528 control subjects without these diseases in a public hospital in Durango City, Mexico. Anti-Toxoplasma IgG antibodies were determined in sera from cases and controls using a commercially available enzyme-linked immunoassay.
Anti-T. gondii IgG antibodies were found in 11 (6.3%) of 176 patients suffering from thyroid dysfunction and in 48 (9.1%) of 528 control subjects (OR = 0.66; 95% CI: 0.33–1.31; P = 0.23). Stratification by two groups of age (50 years and younger, and 51 year and older) showed that the youngest group of patients with thyroid dysfunction had a significantly lower seroprevalence of T. gondii infection than its age- and gender-matched control group (1/83: 1.2% vs 23/257: 8.6%; OR = 0.12; 95% CI: 0.01–0.93; P = 0.01). This stratification also showed that the youngest group of patients with hypothyroidism had a significantly lower seroprevalence of T. gondii infection than its age- and gender matched control group (0/75: 0% vs 21/233: 9.0%; P = 0.003).
Our results suggest that thyroid dysfunction is not associated with seropositivity to T. gondii in general; however, in young (50 years or less) patients, a negative association between infection and thyroid dysfunction and hypothyroidism was found. Further research to confirm this negative association is needed.
The purpose of this study was to gather temporal trends on bacteria epidemiology and resistance of intraoperative bone culture from chronic ostemyelitis at an affiliated hospital in South China.
Records of patients with chronic osteomyelitis from 2003 to 2014 were retrospectively reviewed. The medical data were extracted using a unified protocol. Antimicrobial susceptibility testing was carried out by means of a unified protocol using the Kirby-Bauer method, results were analyzed according to Clinical and Laboratory Standards Institute definitions.
Four hundred eighteen cases met our inclusion criteria. For pathogen distribution, the top five strains were Staphylococcus aureus (27.9%); Pseudomonas aeruginosa (12.1%); Enterobacter cloacae (9.5%); Acinetobacter baumanii (9.0%) and Escherichia coli (7.8%). Bacterial culture positive rate was decreased significantly among different year-groups. Mutiple bacterial infection rate was 28.1%. One strain of Staphylococcus aureus was resistant to linezolid and vancomycin. Resistance of Pseudomonas aeruginosa stains to Cefazolin, Cefuroxime, Cefotaxime, and Cefoxitin were 100% nearly. Resistance of Acinetobacter baumanii stains against Cefazolin, Cefuroxime were 100%. Ciprofloxacin resistance among Escherichia coli isolates increased from 25 to 44.4%. On the contrary, resistance of Enterobacter cloacae stains to Cefotaxime and Ceftazidime were decreased from 83.3 to 36.4%.
From 2003 to 2014, positive rate of intraoperative bone culture of chronic osteomyelitis was decreased; the proportion of Staphylococcus aureus was decreased gradually, and our results indicate the importance of bacterial surveilance studies about chronic osteomyelitis.
Hirotsu N, Sakaguchi H, Sato C, et al.
AbstractBackgroundWe assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza.MethodsThis open-label study administered one weigth-adjusted dose of baloxavir to 107 children aged 1–11 years with laboratory-confirmed, febrile influenza virus infection of
Pogue J, Kaye K, Veve M, et al.
AbstractBackgroundCeftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown.MethodsA retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality.ResultsA total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31–5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03–0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4.ConclusionsThese data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.
Prevention of new HIV infections is a critical public health issue. The highest HIV testing gaps are in men, adolescents 15–19 years old, and adults 40 years and older. Community-based HIV testing services (HTS) can contribute to increased testing coverage and early HIV diagnosis, with HIV self-testing (HIVST) strategies showing promise. Community-based strategies, however, are resource intensive, costly and not widely implemented. A community-led approach to health interventions involves supporting communities to plan and implement solutions to improve their health. This trial aims to determine if community-led delivery of HIVST can improve HIV testing uptake, ART initiation, and broader social outcomes in rural Malawi.
The trial uses a parallel arm, cluster-randomised design with group village heads (GVH) and their defined catchment areas randomised (1:1) to community-led HIVST or continue with the standard of the care (SOC). As part of the intervention, informal community health cadres are supported to plan and implement a seven-day HIVST campaign linked to HIV treatment and prevention. Approximately 12 months after the initial campaign, intervention GVHs are randomised to lead a repeat HIVST campaign. The primary outcome includes the proportion of adolescents 15–19 years old who have tested for HIV in their lifetime. Secondary outcomes include recent testing in adults 40 years and older and men; ART initiation; knowledge of HIV prevention; and HIV testing stigma. Outcomes will be measured through cross-sectional surveys and clinic registers. Economic evaluation will determine the cost per person tested, cost per person diagnosed, and incremental cost effectiveness ratio.
To the best of our knowledge, this is the first trial to assess the effectiveness of community-led HTS, which has only recently been enabled by the introduction of HIVST. Community-led delivery of HIVST is a promising new strategy for providing periodic HIV testing to support HIV prevention in rural communities. Further, introduction of HIVST through a community-led framework seems particularly apt, with control over healthcare concurrently devolved to individuals and communities.
Clinicaltrials.gov registry (NCT03541382) registered 30 May 2018.
Batsa Debrah L, Klarmann-Schulz U, Osei-Mensah J, et al.
AbstractBackgroundImproved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200µg/kg) plus albendazole (ALB; 800mg single dose) is superior to IVM alone.MethodsThis trial was performed in Ghana and included 272 microfilaria (MF) -positive participants randomized to 4 treatment arms: 1) IVM annual at 0, 12, and 24 months; 2) IVM semiannual at 0, 6, 12, 18 and 24 months; 3) IVM+ALB annual; 4) IVM+ALB semiannual. Microfiladermia was determined pre-treatment and at 6, 18 and 36 months. The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months.ResultsPost-treatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%) and 20/125 (16.0%) living female worms had normal embryogenesis in the IVM annual, IVM semiannual, IVM+ALB annual and IVM+ALB semiannual groups respectively (p=0.1229). Proportions of dead worms also did not differ between the 4 groups (p=0.9198). Proportions of patients without MF at 36 months (one year after the last treatment) were 35/56 (63%) after annual IVM, 42/59 (71%) after semiannual IVM, 39/64 (61%) after IVM+ALB annual, and 43/53 (81%) after semiannual IVM+ALB.ConclusionsThe combination treatment with IVM plus ALB was no better than IVM alone for sterilizing, killing of adult worms or achieving sustained MF clearance. However, semiannual treatment was superior to annual treatment for achieving sustained clearance of O. volvulus MF from the skin (p=0.024).
Simon, M. S., Sfeir, M. M., Calfee, D. P., Satlin, M. J.
Background: Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown.Methods: We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY.Results: In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively.Conclusion: CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.
Auld S, Maenetje P, Ravimohan S, et al.
AbstractEnd-organ impairment has received relatively little research attention as a possible manifestation of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS). In this prospective cohort study, one-half of adults with human immunodeficiency virus and pulmonary tuberculosis experienced meaningful declines in lung function on antiretroviral therapy, suggesting a role for lung function in TB-IRIS definitions.
Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease.
The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases.
From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available.
The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China.
Swift M, Molella R, Vaughn A, et al.
AbstractBackgroundUS public health strategy for eliminating tuberculosis (TB) prioritizes treatment of latent TB infection (LTBI). Healthcare personnel (HCP) are less willing to accept treatment than other populations. Little is known about factors associated with HCP LTBI therapy acceptance and completion.MethodsWe conducted a retrospective chart review to identify all employees with LTBI at time of hire at a large academic medical center during a 10-year period. Personal demographics, occupational factors, and clinic visit variables were correlated with LTBI treatment acceptance and completion rates using multivariate logistic regression.ResultsOf 470 HCP with LTBI for whom treatment was recommended, 193 (41.1%) accepted treatment, while 137 (29.1%) completed treatment. Treatment adherence was better with 4 months of rifampin than 9 months of isoniazid (95% vs 68%, P < .005). Increased age of the healthcare worker was independently associated with lower rates of treatment acceptance (odds ratio [95% confidence interval]: 0.97 [0.94–0.99] per year), as was having an occupation of clinician (0.47 [0.26–0.85]) or researcher (0.34 [0.19–0.64]). Male gender was associated with higher treatment acceptance (1.90 [1.21–2.99]). Treatment completion was associated with being from a low- (9.49 [2.06–43.73]) or medium- (8.51 [3.93–18.44]) TB-burden country.ConclusionsGeographic and occupational factors affect acceptance and completion of LTBI therapy. Short-course regimens may improve adherence. Physicians, researchers, and HCP from high-TB-burden countries have lower treatment rates than other HCP. Improving LTBI treatment in HCP will require attending to cultural and occupational differences.
Hook E, III, Newman L, Drusano G, et al.
AbstractGonorrhea remains a major public health challenge and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetics/pharmacodynamics contributors to effective therapy and to prevention of antimicrobial resistance, to newer designs for Phase -2 and -3 clinical trials, and is hampered by the requirement to utilize currently recommended combination ceftriaxone/azithromycin therapy as the comparator regimen in non-inferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints likewise hinder enrollment of populations at greatest risk for gonorrhea (adolescents, women, persons infected with antibiotic resistant Neisseria gonorrhoeae). This Viewpoint summarizes a recent meeting to re-consider the evaluation process for antimicrobials for urogenital gonorrhea treatment and highlights these themes to encourage consideration of new designs for evaluation of gonorrhea therapy.
Greaves, W., Wan, H., Yee, K. L., Kandala, B., Vaddady, P., Hwang, C.
Doravirine is a non-nucleoside reverse transcriptase inhibitor approved for the treatment of HIV-1. In a phase 1 trial, doravirine exposure was transiently decreased when treatment was started immediately after stopping efavirenz. In a post-hoc subgroup analysis of participants who switched from an efavirenz-based regimen to doravirine/lamivudine/tenofovir disoproxil fumarate in the phase 3 DRIVE-SHIFT trial, doravirine plasma levels at week 4 were similar to non-induced levels, and HIV-1 suppression was maintained at weeks 24 and 48.
Glaser C, Bloch K.
A CID book review “Red Book: 2006 Report of the Committee on Infectious Diseases, 27th Edition Edited by Larry K. Pickering, Carol F. Baker, Sarah S. Long, and Julia A. McMillan Elk Grove Village, IL: American Academy of Pediatrics, 2006. 992 pp. $124.95 (cloth)” was erroneously published with a duplicate DOI. It has now been republished with a new DOI, 10.1093/cid/44.6.892.
Den Heijer C, Hoebe C, Driessen J, et al.
An error appeared in the initial publication of this article [den Heijer CDJ, Hoebe CJPA, Driessen JHM, et al. Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients. Clin Infect Dis https://doi.org/10.1093/cid/ciz429]. This article was originally published with the following error:
Hage-Sleiman M, Tremeaux P, Fillion M, et al.
AbstractSerological assays were performed on 85 human immunodeficiency virus-controller samples . 6% presented a negative rapid screening test 7% presented an indeterminate Western blot. The enzyme immunoassay ratio decreased in controllers who had continual negative ultrasensitive HIV RNA results since inclusion.
Palms, D. L., Hicks, L. A., Bartoces, M., Hersh, A. L., Zetts, R., Hyun, D. Y., Fleming-Dutra, K. E.
Using the 2014 IBM MarketScan Commercial Database, we compared antibiotic selection for pharyngitis, sinusitis, and acute otitis media in retail clinics, emergency departments, urgent cares, and offices. Only 50% of visits for these conditions received recommended first-line antibiotics. Improving antibiotic selection for common outpatient conditions is an important stewardship target.
The worldwide expansion of macrolide-resistant Mycoplasma genitalium (MG) in cases of genital infections has led to an increased recurrence rate of these infections after first-line azithromycin treatment. By detecting the presence of azithromycin-resistant MG, the patient’s antibiotic treatment can be targeted and the spread of resistance prevented. With this aim in mind, macrolide-resistance detection kits are helpful tools for the physician.
Azithromycin resistance mutations in MG are targeted using a four-color multiplex real-time RT-PCR assay. Tested targets include plasmid DNA (as positive controls) as well as macrolide-sensitive and macrolide-resistant genomic DNA from characterized cell lines and clinical samples.
The analytical data presented here were generated from plasmid DNA and genomic RNA/DNA and include adaptation to an internal control, specificity between targets, specificity vs non-MG species, limit of detection (LoD) and interference studies (co-infection and endogenous substances). The clinical data were based on the application of the assay to clinical samples characterized by sequencing.
A new NAAT (nucleic acid amplification test) prototype has been developed in collaboration with the Diagenode s.a. company, this prototype targets MG and azithromycin-resistance mutations in that pathogen.
Shearer, J. D., Saylor, M. L., Butler, C. M., Treston, A. M., Heine, H. S., Chirakul, S., Schweizer, H. P., Louie, A., Drusano, G. L., Zumbrun, S. D., Warfield, K. L.
Burkholderia pseudomallei (B. pseudomallei), the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care, but in the case of septicemia left untreated it can range from 50 – 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for two weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase melioidosis is needed. GC-072 is a potent, 4-oxoquinolizine antibiotic with selective inhibitory activity against bacterial topoisomerases. GC-072 has demonstrated in vitro potency against susceptible and drug-resistant strains of B. pseudomallei and is also active against Burkholderia mallei, Bacillus anthracis, Yersinia pestis, and Francisella tularensis. GC-072 is bactericidal both extra- and intracellularly, with rapid killing noted within a few hours and reduced development of resistance compared to ceftazidime. GC-072, delivered intragastrically to mimic oral administration, promoted dose-dependent survival in mice using lethal inhalational models of B. pseudomallei infection following exposure to a 24 or 339 LD50 challenge with B. pseudomallei strain 1026b. Overall, GC-072 appears to be a strong candidate for first-line, oral treatment of melioidosis.
Jacobsson, S., Kularatne, R., Kittiyaowamarn, R., Maseko, V., Paopang, P., Sangprasert, P., Sirivongrangson, P., Piddock, L., Wi, T., Alirol, E., Unemo, M.
We evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n=99; 2018) and South Africa (n=100; 2015-2017). Zoliflodacin was highly active in vitro against all tested isolates (MIC range: 0.004-0.25; MIC50: 0.064, MIC90: 0.125 μg/ml), with no cross-resistance to any of the seven comparator antimicrobials. Our data support the initiation of the global zoliflodacin phase 3 randomized controlled clinical trial for uncomplicated gonorrhea.
Otieno G, Bottomley C, Khagayi S, et al.
AbstractIntroductionMonovalent rotavirus vaccine, RotarixTM, was introduced in Kenya in July 2014, is recommended to infants as oral doses at ages 6 and 10 weeks. A multi-site study was established in two population based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalisations (RVH).MethodsHospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhoea hospitalisations among children aged
The emergence of Drug-Resistance Tuberculosis (DR-TB) is an increasing global public health problem. Lost to Follow-up (LTFU) from DR-TB treatment remains a major barrier to tuberculosis epidemic control and better treatment outcome. In Ethiopia, evidences on the incidence and predictors of LTFU are scarce. Thus, this study aimed to determine the incidence and identify the predictors of LTFU among DR-TB patients.
A retrospective follow-up study was conducted among a total of 332 DR-TB patients at the University of Gondar comprehensive specialized hospital. Data were retrieved from patient records from September 2010 to December 2017 and entered in to Epi-data 126.96.36.199 and analysed using Stata14.1 software. The risk was estimated using the Nelson-Aalen cumulative hazard curve. A log-rank test was used for survival comparisons between categories of independent variables. The Gompertz regression model was fitted, and hazard ratio with a 95% confidence interval (CI) was used to measure the strength of associations. Variables with less than 0.05 p-values in the multivariable model were considered as significantly associated with LTFU.
Among a total of 332 patient records reviewed, 206 (62.05%) were male. The median age was 30 years (Inter Quartile Range (IQR): 23–40). Forty-one (12.35%) of the participants had no history of TB treatment, while a quarter of were TB-HIV co-infected. Closely all (92.17%) of the patients had pulmonary tuberculosis. The median follow up time was 20.37 months (IQR: 11.02, 21.80). Thirty-six (10.84%) patients were lost from follow-up with an incidence rate of 6.47 (95% CI: 4.67, 8.97)/1000 Person Months (PM). Homelessness (Adjusted Hazard Ratio (AHR) =2.51, 95%CI: 1.15, 5.45) and treatment enrolment year from 2013 to 2014 (AHR = 3.25, 95% CI: 1.30, 8.13) were significant predictors of LTFU.
This study indicated that LTFU among DR-TB registered patients was high in the first six months compared to subsequent months. Homelessness and year of treatment enrolment were independent predictors of LTFU, requiring more economic support to patients in order to ensure treatment completion. This result can be generalized to patients who are using DR-TB treatment in similar settings.
Cellulosimicrobium species, formely known as Oerskovia species, are gram-positive bacilli belonging to the order Actinomycetales. They rarely cause human infections. The genus comprises two pathogenic species in humans: C. cellulans and C. funkei. Based on a case report, we provide a review of the literature of infections caused by Cellulosimicrobium/Oerskovia, in order to improve our knowledge of this unusual infection.
An 82-year-old woman with aortic prosthetic valve presented to the hospital with fever and heart failure. Further work up revealed the diagnosis of C. cellulans infective endocarditis (IE). The strain was identified by MALDI-TOF MS, API Coryne and 16S rRNA sequencing. The patient was deemed not to be an operative candidate and died despite the antibiotic therapy 35 days after admission.
Reviewing cases of Cellulosimicrobium species infections and communicating the successful and unsuccessful clinical experiences can assist future healthcare providers. Our case and those previously reported indicate that Cellulosimicrobium species usually infect immunocompromised patients or foreign body carriers. The most frequent pattern of infection is central venous catheter related bacteremia. The optimal treatment should include foreign body removal and valve surgery should be considered in case of IE.
Multi-drug resistant Tuberculosis (MDR-TB) is a strain of Mycobacterium tuberculosis that is resistant to at least Rifampicin and Isoniazid drugs. The treatment success rate for MDR-TB cases is lower than for drug susceptible TB. Globally only 55% of MDR-TB patients were successfully treated. Monitoring the early treatment outcome and better understanding of the specific reasons for early unfavorable and unknown treatment outcome is crucial for preventing the emergence of further drug-resistant tuberculosis. However, this information is scarce in Ethiopia. Therefore, this study aimed to determine the intensive phase treatment outcome and contributing factors among patients treated for MDR-TB in Ethiopia.
A 6 year retrospective cohort record review was conducted in fourteen TICs all over the country. The records of 751 MDR-TB patients were randomly selected using simple random sampling technique. Data were collected using a pre-tested and structured checklist. Multivariable multinomial logistic regression was undertaken to identify the contributing factors.
At the end of the intensive phase, 17.3% of MDR-TB patients had an unfavorable treatment outcome, while 16.8% had an unknown outcome with the remaining having a favorable outcome. The median duration of the intensive phase was 9.0 months (IQR 8.04–10.54). Having an unfavorable intensive phase treatment outcome was found significantly more common among older age [ARRR = 1.047, 95% CI (1.024, 1.072)] and those with a history of hypokalemia [ARRR = 0.512, 95% CI (0.280, 0.939)]. Having an unknown intensive phase treatment outcome was found to be more common among those treated under the ambulatory care [ARRR = 3.2, 95% CI (1.6, 6.2)], rural dwellers [ARRR = 0.370, 95% CI (0.199, 0.66)], those without a treatment supporter [ARRR = 0.022, 95% CI (0.002, 0.231)], and those with resistance to a limited number of drugs.
We observed a higher rate of unfavorable and unknown treatment outcome in this study. To improve favorable treatment outcome more emphasis should be given to conducting all scheduled laboratory monitoring tests, assignment of treatment supporters for each patient and ensuring complete recording and reporting which could be enhanced by quarterly cohort review. Older aged and rural patients need special attention. Furthermore, the sample referral network should be strengthened.
Steele A, Groome M.
Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known.
This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged
Krahn T, Sebastiani G.
Reports on the worldwide ascending trend of pulmonary nontuberculous mycobacteria (NTM) isolation rates and their effective role in respiratory tract infections are compelling. However, as yet, there are no such data relating to Tunisia.
Here we carried out a retrospective review of mycobacterial cultures originating from Northern Tunisia, which have been processed in the laboratory of mycobacteria of the Institut Pasteur de Tunis, during the time period 2002–2016. All pulmonary NTM (PNTM) isolates available for culture were characterized phenotypically and their taxonomic status was further established based on polymorphisms in rpoB, 16S rRNA, hsp65, and sodA DNA gene sequences.
Of the 10,466 specimens collected from HIV-negative Tunisian patients with presumptive clinical pulmonary TB, 60 (0.6%) yielded PNTM isolates. An overall annual PNTM isolation prevalence of 0.2/100,000 was estimated. As far as could be ascertained, this isolation rate accounts amongst the lowest reported hitherto throughout the world. Among the 30 NTM isolates that were available for culture, 27 (90.0%) have been identified to the species level. The most commonly encountered species was Mycobacterium kansasii (23.3%) subtype 1. Strikingly, all M. kansasii cases were male patients originating from Bizerte, an industrialized region particularly known for iron industry. The remaining NTM species were M. fortuitum (16.6%), M. novocastrense (16.6%), M. chelonae (10.0%), M. gordonae (6.6%), M. gadium (6.6%), M. peregrinum (3.3%), M. porcinum (3.3%), and M. flavescens (3.3%). There were no bacteria of the M. avium complex, the most frequently isolated NTM globally, and the main driver of the rise of NTM-lung diseases.
This study uncovered an exceptional low prevalence of PNTM isolation among HIV-negative TB suspects in Northern Tunisia, suggesting a very low burden of NTM pulmonary disease. However, the frequent isolation of M. kansasii subtype 1, the most pathogenic subtype, particularly from the industrialized region of Bizerte, strongly suggests its effective involvement in a typical pulmonary disease.
Behillil S, May F, Fourati S, et al.
AbstractIn a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day-28 mortality than others (80% vs 12%; p=0.011).
Thompson, E. J., Wu, H., Melloni, C., Balevic, S., Sullivan, J. E., Laughon, M., Clark, K. M., Kalra, R., Mendley, S., Payne, E. H., Erinjeri, J., Gelber, C. E., Harper, B., Cohen-Wolkowiez, M., Hornik, C. P., on behalf of the Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
Doxycycline is a tetracycline-class antimicrobial labeled by the United States (U.S.) Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline class antibiotics and tooth staining, although doxycycline may be used off-label in severe conditions. Accordingly, there is a paucity of pharmacokinetic (PK) data to guide dosing in children 8 years and younger. We leveraged opportunistically-collected plasma samples after intravenous (IV) and oral doxycycline doses received per standard of care to characterize the PK of doxycycline in children of different ages, and evaluated the effect of obesity and fasting status on PK parameters.We developed a population PK model of doxycycline using data collected from 47 patients 0–18 years of age, including 14 participants ≤8 years. We developed a 1 compartment PK model and found doxycycline clearance to be 3.32 L/h/70 kg and volume to be 96.8 L/70kg for all patients; comparable to values reported in adults. We estimated a bioavailability of 89.6%, also consistent with adult data. Allometrically scaled clearance and volume of distribution did not differ between children 2 to ≤8 years of age and children >8 to ≤18 years of age, suggesting that younger children may be given the same per kg dosing. Obese and fasting status were not selected for inclusion in the final model. Additional doxycycline PK samples collected in future studies may be used to improve model performance and maximize its clinical value.
Kullar R, Nagel J, Bleasdale S, et al.
Yki-Järvinen H, Lallukka-Brück S, Sutinen J.
Whitley R, Monto A.
Nalwoga A, Nakibuule M, Marshall V, et al.
AbstractIntroductionDetectable KSHV DNA in blood and increased antibody titres may indicate KSHV reactivation, while transmission of KSHV occurs via viral shedding in saliva.MethodsWe investigated risk factors for KSHV DNA detection by real-time PCR, in blood and viral shedding in saliva, in 878 people aged 3 to 89 years of both sexes in a rural Ugandan population cohort. Helminths were detected using microscopy and malaria parasitaemia was identified using rapid diagnostic tests. Regression modelling was used for statistical analysis.Resultsand discussion: KSHV viral load in blood did not correlate with viral load in saliva, suggesting separate immunological control within each compartment. The proportion of individuals with detectable virus in blood was 23% among children aged 3-5 years , 22% among 6-12 years old, thereafter reducing with increasing age. The proportion of individuals with detectable virus in saliva increased from 30% in 3-5 year old children to 45% in those aged 6-12 and decreasing subsequently with increasing age. Overall, 29% of males shed in saliva compared to 19% of females (p = 0.008). Together, these data suggest that young males may be responsible for much of the onward transmission of KSHV. Individuals with a current malaria infection had higher levels of viral DNA in blood (p = 0.031) compared to malaria uninfected individuals. This suggests that malaria may lead to KSHV reactivation, thereby increasing transmission and pathogenicity of the virus.
Hepatitis C virus (HCV) is common in men who have sex with men (MSM) with HIV. The Swiss HCVree Trial targeted a micro-elimination by using a treat and counsel strategy. Self-reported condomless anal intercourse with non-steady partners was used as the selection criterion for participation in a counselling intervention designed to prevent HCV re-infection. The purpose of this study was to assess the ability of this criterion to identify men who engaged in other sexual risk behaviours associated with HCV re-infection.
Men who disclosed their sexual and drug- use behaviours during the prior 6 months, at study baseline, were included in the current study. Using a descriptive comparative study design, we explored self-reported sexual and drug-use risk behaviours, compared the odds of reporting each behaviour in men who reported and denied condomless anal intercourse with non-steady partners during the prior year and calculated the sensitivity/specificity (95% CI) of the screening question in relation to the other at-risk behaviours.
Seventy-two (61%) of the 118 men meeting eligibity criteria reported condomless anal intercourse with non-steady partners during the prior year. Many also engaged in other potential HCV transmission risk behaviours, e.g., 52 (44%) had used drugs. In participants disclosing drug use, 44 (37%) reported sexualised drug use and 17 (14%) injected drugs. Unadjusted odds ratios (95% CI) for two well-known risk behaviours were 2.02 (0.80, 5.62) for fisting and 5.66 (1.49, 37.12) for injecting drug use. The odds ratio for sexualised drug use - a potential mediator for increased sexual risk taking - was 5.90 (2.44, 16.05). Condomless anal intercourse with non-steady partners showed varying sensitivity in relation to the other risk behaviours examined (66.7–88.2%).
Although condomless anal intercourse with non-steady partners was fairly sensitive in detecting other HCV relevant risk behaviours, using it as the only screening criterion could lead to missing a proportion of HIV-positive men at risk for HCV re-infection due to other behaviours. This work also points to the importance of providing access to behavioral interventions addressing other sexual and drug use practices as part of HCV treatment.
Clinical Trial Number: NCT02785666, 30.05.2016.
Wolf A, Padayatchi N, Naidoo K, et al.
AbstractDetection of spatiotemporal heterogeneity loci in tuberculosis (TB) cases (‘clusters’) using routine microbiological data from KwaZulu-Natal, South Africa may provide insight into transmission dynamics and allow for efficient deployment of public health resources. Using an open-access spatiotemporal analytics program, we mapped clusters, dynamic changes, and characterized drug-resistant TB clustering risk.
Bordetella pertussishuman challengevaccineimmunitypathogenesis
Galgiani J, Blair J, Ampel N, et al.
AbstractThe care of primary pulmonary coccidioidomycosis remains challenging. Such infections produce a variety of signs, symptoms, and serologic responses that cause morbidity in patients and concern in treating clinicians for the possibility of extrapulmonary dissemination. Illness may be due to ongoing fungal growth that produces acute inflammatory responses, resulting in tissue damage and necrosis, and for this, administering an antifungal drug may be of benefit. In contrast, convalescence may be prolonged by other immunologic reactions to infection, even after fungal replication has been arrested, and in those situations, antifungal therapy is unlikely to yield clinical improvement. In this presentation, we discuss what findings are clinical indicators of fungal growth and what other sequalae are not. Understanding these differences provides a rational management strategy for deciding when to continue, discontinue, or reinstitute antifungal treatments.
Du Y, Qiu C, Chen X, et al.
AbstractBackgroundThe emergence of multidrug-resistant tuberculosis (MDR-TB) poses a serious obstacle to global TB control programmes.MethodsWe carried out a prospective, randomised multicenter study in China focused on the potential of shorter regimen containing clofazimine (CFZ) for the treatment of MDR-TB. 135 MDR-TB cases met eligibility requirements and were randomly stratified into control group or experimental group. Patients in the control group received 18-month treatment regimen, whereas patients in the experimental group received 12-month treatment regimen containing CFZ.ResultsAt the completion of treatment period, the difference in sputum-culture conversion between the experimental group and the control group was not significant. Notably, by the end of the 3-month treatment, 68.7% patients receiving experimental regimen had sputum-culture conversion as compared with 55.9% of those receiving control regimen; this was a significant difference, suggesting an early sputum conversion (P=0.04). 67 adverse events were reported in 56 patients in this study, including 32 in the control group and 35 in the experimental group, respectively. No significant difference in the overall incidence of adverse events was observed between the two groups.ConclusionThe MDR-TB patients initiated with the shorter regimen containing CFZ have a comparable successful outcome rate when compared to those with the standard regimen. The patients assigned in the experimental group achieve more rapid sputum culture conversion, reflecting the superior antimicrobial activity against MDR-TB.
The 2014–2016 Ebola epidemic in West Africa was the largest Ebola epidemic to date. Contact tracing was a core surveillance activity. Challenges with paper-based contact tracing systems include incomplete identification of contacts, delays in communication and response, loss of contact lists, inadequate data collection and transcription errors.
The aim of this study was to design and evaluate an electronic system for tracing contacts of Ebola cases in Port Loko District, Sierra Leone, and to compare this with the existing paper-based system. The electronic system featured data capture using a smartphone application, linked to an alert system to notify the District Ebola Response Centre of symptomatic contacts.
The intervention was a customised three-tier smartphone application developed using Dimagi’s CommCare platform known as the Ebola Contact Tracing application (ECT app). Eligible study participants were all 26 Contact Tracing Coordinators (CTCs) and 86 Contact Tracers (CTs) working in the 11 Chiefdoms of Port Loko District during the study period (April–August 2015). Case detection was from 13th April to 17th July 2015. The CTCs and their CTs were provided with smartphones installed with the ECT app which was used to conduct contact tracing activities. Completeness and timeliness of contact tracing using the app were compared with data from April 13th-June 7th 2015, when the standard paper-based system was used.
For 25 laboratory-confirmed cases for whom paper-based contact tracing was conducted, data for only 39% of 408 contacts were returned to the District, and data were often incomplete. For 16 cases for whom app-based contact tracing was conducted, 63% of 556 contacts were recorded as having been visited on the app, and the median recorded duration from case confirmation to first contact visit was 70 h.
There were considerable challenges to conducting high-quality contact tracing in this setting using either the paper-based or the app-based system. However, the study demonstrated that it was possible to implement mobile health (mHealth) in this emergency setting. The app had the benefits of improved data completeness, storage and accuracy, but the challenges of using an app in this setting and epidemic context were substantial.
Crowell T, Pinyakorn S, Sacdalan C, et al.
AbstractTransient viral blips ≥20 copies/mL were observed in 16.9% of acutely-treated HIV-infected adults in Thailand. Blip incidence increased from 0.0 (95% confidence interval 0.0-2.9)/100 person-years after ART in Fiebig I to 15.9 (7.6-29.2) in Fiebig V. Increasing viral load and Fiebig stage at ART initiation were independently predictive of blips.
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Frailty is associated with insulin resistance in chronic HIV
15.10.2019Clinical Infectious Diseases Advance Access
CD40 polymorphisms were associated with HCV infection susceptibility among Chinese population
15.10.2019Latest Results for BMC Infectious Diseases
The first case of Acrophialophora levis -induced severe pneumonia: a case report and literature review
15.10.2019Latest Results for BMC Infectious Diseases
First insights into the genetic characteristics and drug resistance of Mycobacterium tuberculosis population collected during the first national tuberculosis prevalence survey of Lao PDR (2010–2011)
15.10.2019Latest Results for BMC Infectious Diseases
Blood stream infections associated with central and peripheral venous catheters
15.10.2019Latest Results for BMC Infectious Diseases
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