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Abstract Background 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. Methods 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. Discussion 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. Trial registration ACTRN12619000309189.…

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

Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration Registered at the Pan African Clinical Trial Registry (www.pactr.org) on April 13, 2018 (retrospectively registered). Trial identification number: PACTR201804003327269.…

Wolf J, Margolis E.

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

Abstract Background The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs. Method 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. Results 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 

Abstract Background 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. Methods 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. Results 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). Conclusions 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.…

Abstract Background 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. Method 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. Result 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%. Conclusions 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

Abstract Background 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. Methods 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. Discussion 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. Trial registration 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).

Abstract Background Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. Methods 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. Results 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. Conclusions 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.…

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.

Rouhani S, Griffin N, Yori P, et al.

AbstractBackgroundDetrimental effects of diarrhea on child growth and survival are well-documented but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration and childhood growth in the Peruvian Amazon.MethodsGrowth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children from 0-24m. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S rRNA genes in fecal samples collected at 6, 12, 18, and 24 months. Linear and generalized linear models were used to investigate whether diarrhea was associated with altered microbiota and in turn if features of the microbiota were associated with the subsequent risk of diarrhea.ResultsDiarrheal frequency, duration, and severity were negatively associated with bacterial diversity and richness (p

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.

Rouhani S, Griffin N, Yori P, et al.

AbstractBackgroundCampylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.MethodsCampylobacter was identified using a broadly reactive, genus-specific ELISA. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at 6,12,18, and 24 months of age (n=928). Associations between infection, growth, and gut microbial community composition were investigated using multiple linear regression adjusting for within-child correlations, age and breastfeeding. Indicator species analyses identified taxa specifically associated with Campylobacter burden.ResultsNinety-three percent (251) of children had Campylobacter present in asymptomatic fecal samples during the follow-up period, and a 10% increase in the proportion of stools infected was associated with mean reductions of 0.02 length-for-age Z scores (LAZ) at 3, 6 and 9 months thereafter (p

Abstract Background Hepatitis B virus (HBV) infection is a major public health problem in China. Over a decade has passed since the last National Hepatitis Seroepidemiological Survey was conducted in 2006. The lack of updated data on hepatitis B in China makes assessing the current prevalence and burden of the disease inadequate. In response to the above situation, a systematic review and meta-analysis was conducted to provide a better understanding of hepatitis B epidemiology in the general population of China. Methods A systematic search was conducted in international databases (Medline through PubMed, EMBASE, Cochrane, Web of Science) and national databases (CBM, CNKI, WanFang Data) to retrieve primary studies published between January 1, 2013 and December 31, 2017. The pooled prevalence of HBV infection and 95% confidence intervals were calculated. Quality assessment, heterogeneity testing and publication bias assessment were also performed. Results Of the 27 studies included in the meta-analysis, the pooled estimated prevalence of HBV infection in the general population of China from 2013 to 2017 was 6.89% (95% CI:5.84–7.95%), which could be extrapolated to an estimated population of 84 million living with HBsAg in 2018. The prevalence of HBV infection in males was higher than that in females (5.88% vs 5.05%), and rural areas had a higher prevalence than urban areas (5.86% vs 3.29%). The highest prevalence of HBV infection was reported in Western provinces (8.92, 95% CI: 7.19–10.64%). In adults older than 20 years, the prevalence of HBV infection was approximately 7%, which was higher than that in children. Conclusion The prevalence of HBV infection in the general population of China was classified as higher intermediate prevalence (5–7.99%), of which more than 90% of the HBV infection population included adults older than 20 years. The blocking of mother-to-infant hepatitis B transmission and plans involving timely birth dose of hepatitis B vaccine within 24 h should be implemented. Additionally, improving the quality of life and survival rate of the infected population through antiviral therapy and high-risk adult vaccination will be the priority of our future work. Moreover, various control measures should be implemented in different provinces across China.…

Abstract Background 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. Methods 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 4.2.0.0 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. Results 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. Conclusion 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.…

Abstract Background 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. Case presentation 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. Conclusions 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.…

Abstract Background 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. Methods 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. Results 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. Conclusion 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.…

Abstract Background 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. Methods 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.

Abstract Background 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. Methods 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. Results 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. Conclusions 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).

Sfeir M.

Abstract Background Elite controllers (EC), a small subset of the HIV-positive population (

Kullar R, Nagel J, Bleasdale S, et al.

Spellberg B, Wald-Dickler N.

To the Editor—We thank Hughes et al [1] for their interest in our editorial emphasizing the mantra that “Shorter Is Better” [2].

Fernandez-Lazaro C, Langford B, Schwartz K.

To the Editor—We thank Hughes et al [1] for their interest in our study [2] and thoughtful commentary on some of the important limitations in the clinical trials cited by Wald-Dickler and Spellberg [3]. One of these limitations, as aptly pointed out by Hughes et al, is that for patients to be randomized and therefore included in the trials, they had to demonstrate clinical improvement prior to randomization. Patients with cellulitis who are not improving by day 5 should clearly not be candidates for 5 days of therapy. Translating trial data into clinical practice is often challenging and “indication creep” can have serious consequences [4]. It is critical that clinicians appreciate the sometimes limited inclusion criteria when incorporating clinical trial data into their practice. Follow-up should be part of routine outpatient care, which allows clinicians to reassess the diagnosis in patients not improving, and advise stoppage of therapy for those improved.

Yki-Järvinen H, Lallukka-Brück S, Sutinen J.

Whitley R, Monto A.

Abstract Background Rubella is an RNA virus in the genus Rubivirus within the Matonaviridae family. Rubella remains a leading vaccine-preventable cause of birth defects. Most African countries including Liberia do not currently provide rubella-containing vaccine (RCV) in their immunization program. We analyzed the existing surveillance data to describe rubella cases and identify the at-risk population. Methods We conducted a retrospective descriptive statistics on the suspected-measles case-based surveillance data that obtained from the national database. Suspected-measles cases who were negative and indeterminate for measles IgM and tested for rubella IgM were extracted from the database. We used only rubella IgM positive cases to calculate trends and percentages by person, place and time. The cumulative-percent curve was used to visually describe the age distribution of rubella cases. Results During 2017–2018, a total of 2027 suspected-measles cases with known laboratory results were reported; of which, 1307 were tested for rubella IgM. Among tested cases, 472 (36%) were positive, 769 (59%) were negative and 66 (5%) were indeterminate for rubella IgM. Female contributed 269 (57%) of the confirmed rubella cases respectively. The median age was 7 years with an interquartile range of 5–10 years. From the total rubella cases, 6 (1%) were under 1 year, 109 (23%) were 1–4 years, 207 (44%) were 5–9 years, 87 (18%) were 10–14 years and 56 (12%) were more than or equal to 15 years. Women in their reproductive-age contributed 23 (5%) of rubella cases with 17% positivity rate. Two-thirds or 307 (65%) of the cases were reported from February to May which is dry season in Liberia. Conclusions Our analysis revealed that rubella was widely circulating in Liberia. Majority of the cases were reported among children

Abstract Background 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. Methods 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. Results 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%). Conclusions 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. Trial registration Clinical Trial Number: NCT02785666, 30.05.2016.…

Hughes S, Kamranpour P, Gibani M, et al.

To the Editor—We read with interest the work by Fernandez-Lazaro et al [1] and accompanying editorial by Wald-Dickler and Spellberg [2]. For many indications, there is a wealth of data to support shorter courses of antimicrobials offering noninferior outcomes while reducing risk factors for antimicrobial resistance, Clostridioides difficile infection, and drug-related adverse reactions. As Wald-Dickler and Spellberg [2] discuss in their editorial, translating this message to prescribers—and ensuring implementation across healthcare settings—is challenging and requires a multimodal approach. We agree with Wald-Dickler and Spellberg [2] that arbitrary 1- or 2-week durations should no longer be advised. However, we contend that a set duration—however short—is not likely to be appropriate for many patients. Response to therapy is likely to depend on a range of host-, pathogen-, and drug-specific factors. Prospective trial-based set durations, even if reassuringly short, oversimplify real-world data. While we broadly agree that “shorter is better,” treatment should aim to achieve the right drug, for the right patient, at the right dose—as well as for the right duration.

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.

Stine O.

Schechter M, Kempker R.

diabetic foot infectionosteomyelitisguidelines…

Abstract Background 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. Methods 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. Results 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. Conclusion 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.…