Tal Brosh-Nissimov

Evaluation of a Benchtop HIV Ultradeep Pyrosequencing Drug Resistance Assay in the Clinical Laboratory

ABSTRACT Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in clinical practice. Ultradeep pyrosequencing has shown to be effective in detecting such mutations. The lack of a standardized commercially based assay limits the wide use of this method in clinical settings. 454 Life Sciences (Roche) is developing an HIV ultradeep pyrosequencing assay for their benchtop sequencer. We assessed the prototype plate in the clinical laboratory. Plasma samples genotyped by the standardized TruGene kit were retrospectively tested by this assay. Drug-treated subjects failing therapy and drug-naive patients were included. DRM analysis was based on the International AIDS Society USA DRM list and the Stanford algorithm. The prototype assay detected all of the DRMs detected by TruGene and additional 50 low-abundance DRMs. Several patients had low-abundance D67N, K70R, and M184V reverse transcriptase inhibitor mutations that persisted long after discontinuation of the drug that elicited these mutations. Additional patient harbored low-abundance V32I major protease inhibitor mutation, which under darunavir selection evolved later to be detected by TruGene. Stanford analysis suggested that some of the low-abundance DRMs were likely to affect the resistance burden in these subjects. The prototype assay performs at least as well as TruGene and has the advantage of detecting low-abundance drug resistance mutations undetected by TruGene. Its ease of use and lab-scale platform will likely facilitate its use in the clinical laboratory. The extent to which the detection of low-abundance DRMs will affect patient management is still unknown, but it is hoped that use of such an assay in clinical practice will help resolve this important question.

Efficacy of urine alkalinization by oral administration of sodium bicarbonate: a prospective open-label trial

BACKGROUND Urine alkalinization is indicated for various medical conditions. Alkalinization is usually achieved by intravenous administration of alkali substances titrated by repeated urinalyses. Some situations such as mass casualty events might require urine alkalinization by the oral route. We evaluated the efficacy of oral sodium bicarbonate administration for urine alkalinization. METHODS In a prospective open-label trial, 4 g of sodium bicarbonate was administered orally 3 times daily to 9 healthy volunteers for 24 hours. Serial blood and urine samples were collected, and urine pH was evaluated. Plasma electrolytes and pH were also measured for safety purposes. RESULTS All participants had a urine pH of at least 7 after 10 hours. At 20 hours, all participants had a urine pH of at least 8. No adverse effects or abnormal blood results were documented during the 24-hour follow-up. CONCLUSIONS Oral administration of a standard dose of sodium bicarbonate tablets resulted in effective urine alkalinization. Further research is needed to investigate the natural course of urine pH after cessation of our protocol and the efficacy of longer periods of treatment.

The association between self-perceived proficiency of personal protective equipment and objective performance: An observational study during a bioterrorism simulation drill

Highlights:We compared between self‐perceived proficiency of PPE use and objective performance.• There was no correlation between comfort and objective performance scores.• Clinics personnel performed better than hospital personnel.• Self‐perceived proficiency is a poor predictor of appropriate PPE use. Background The recent Ebola virus disease outbreak emphasized the potential misuse of personal protective equipment (PPE) by health care workers (HCWs) during such an event. We aimed to compare self‐perceived proficiency of PPE use and objective performance, and identify predictors of low compliance and PPE misuse. Methods: An observational study combined with subjective questionnaires were carried out during a bioterror simulation drill. Forty‐two observers evaluated performance under PPE. Mistakes were recorded and graded using a structured observational format and were correlated with the subjective questionnaires and with demographic parameters. Results: One hundred seventy‐eight HCWs from community clinics and hospitals were included. The mean self‐perceived proficiency was high (6.1 out of 7), mean level of comfort was moderate (4.0 out of 7), and mean objective performance was intermediate (9.5 out of 13). There was no correlation between comfort and objective performance scores. Self‐perceived proficiency was in correlation with donning and continuous performance with PPE but not with doffing. Clinic personnel performed better than personnel in hospitals (40.3% vs 67.8% with 3 or more mistakes, respectively; P = .001). Demographic characteristics had no correlation with objective or self‐perceived performance. Conclusions: Self‐perceived proficiency is a poor predictor of appropriate PPE use. The results suggest poor awareness of the possibility of PPE misuse.

Lassa fever: another threat from West Africa

Lassa fever, a zoonotic viral infection, is endemic in West Africa. The disease causes annual wide spread morbidity and mortality in Africa, and can be imported by travelers. Possible importation of Lassa fever and the potential for the use of Lassa virus as an agent of bioterrorism mandate clinicians in Israel and other countries to be vigilant and familiar with the basic characteristics of this disease. The article reviews the basis of this infection and the clinical management of patients with Lassa fever. Special emphasis is given to antiviral treatment and infection control.

Candida auris Infection Leading to Nosocomial Transmission, Israel, 2017

A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogenetic analysis showed resemblance of C. auris to isolates from South Africa but not Israel, suggesting travel-associated infection. C. auris infection occurred weeks later in another patient at the same hospital, suggesting prolonged environmental persistence.

Estimated prevalence of smallpox vaccine contraindications in Israeli adolescents

BACKGROUND Routine smallpox vaccination for military recruits was discontinued in Israel in 1996. However, Israeli guidelines recommend post-event mass-vaccination. This study aimed to estimate the rate of Israeli adolescents at risk of severe adverse events after vaccination during 1998-2013. METHODS The study population included adolescents screened before military service in 1998-2013. Medical parameters correlating with contraindications to smallpox vaccination were retrieved from army databases, and were categorized by severity according to the Israeli post-event strategy. RESULTS Of 1,180,964 individuals, 1.86% had vaccination contraindications in a post-event scenario. An additional 1.24% had contraindications in a pre-event scenario. There was an increase in the percentage of contraindications over time, attributed to the rising incidence of atopic-dermatitis. CONCLUSIONS Only a small percentage of the adolescent population is ineligible to receive the smallpox vaccine currently in use. This group may be protected by herd-immunity, or by new-generation vaccines designed to prevent severe adverse events.

Preparing for imported Ebola cases in Israel, 2014 to 2015

During the current outbreak of Ebola virus disease (EVD) in West Africa, preventing exportation of the disease posed many challenges for economically more developed countries. In Israel, although the risk of importing single cases was assumed to be low, the implications of local transmission were great. This article describes the EVD preparedness plan of the Israeli Ministry of Health. Key elements were a sensitive case definition, designation of a single treatment centre for suspected and confirmed cases, construction of a mobile unit using customised negative-pressure tents and a vigorous national training programme. There were no patients with EVD in Israel, but a few suspected cases were assessed. The Israeli plan may provide a template for emergency infectious disease response in other geographically small countries.

Management of sexually transmissible infections in the era of multiplexed molecular diagnostics: a primary care survey

Background Data regarding sexually transmissible infections (STI) often originate from STI clinics, screening programs or laboratory-based studies, thus are biased for specific risk groups or lack clinical details. This real-life observational study presents sample data of most young adult Israeli population by exploiting the centralised diagnostic and documentation platforms resulting from a mandatory military service at the age of 18 years for both genders. METHODS All STI diagnoses of Israeli Defence Forces soldiers during a 6-month period were reviewed. Patients with Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) (major-STI) and Ureaplasma urealyticum (UU), Ureaplasma parvum (UP) and Mycoplasma hominis (MH) (equivocal STI) were compared with STI-negative controls. RESULTS Sexually transmissible infection positivity rates (n=2816) were as follows: CT 6.6%; MG 1.9%; NG 0.7%; TV 0.5%; UU 15.7%; UP 28.2%; and MH 6.2%. The CT+MG coinfection rate was 4.1%, yet CT+NG coinfections were rare (≈0.5%). More than half of the patients with ureaplasmas and/or MH were treated; 40% of them were recommended partner treatment. Most antibiotics were prescribed to patients with equivocal infections. Classic STI symptoms in males were linked to major-STI and UU, while females were asymptomatic or presented non-specific symptoms. CONCLUSIONS The judicious use of antibiotics in the era of antimicrobial resistance necessitates re-evaluating the significance of equivocal pathogen detection and reporting (MH, UU, UP). Likewise, universal empiric treatment for NG should be reconsidered in light of its low rates in non-high-risk groups. Conversely, a high MG rate, a pathogen with potential resistance to common STI protocols, requires evaluation of guidelines adequacy.

Medicine and the Holocaust: a visit to the Nazi death camps as a means of teaching medical ethics in the Israel Defense Forces Medical Corps

A novel method of teaching military medical ethics, medical ethics and military ethics in the Israel Defense Force (IDF) Medical Corps, essential topics for all military medical personnel, is discussed. Very little time is devoted to medical ethics in medical curricula, and even less to military medical ethics. Ninety-five per cent of American students in eight medical schools had less than 1 h of military medical ethics teaching and few knew the basic tenets of the Geneva Convention. Medical ethics differs from military medical ethics: the former deals with the relationship between medical professional and patient, while in the latter military physicians have to balance between military necessity and their traditional priorities to their patients. The underlying principles, however, are the same in both: the right to life, autonomy, dignity and utility. The IDF maintains high moral and ethical standards. This stems from the preciousness of human life in Jewish history, tradition and religious law. Emphasis is placed on these qualities within the Israeli education system; the IDF teaches and enforces moral and ethical standards in all of its training programmes and units. One such programme is ‘Witnesses in Uniform’ in which the IDF takes groups of officers to visit Holocaust memorial sites and Nazi death camps. During these visits daily discussions touch on intricate medical and military ethical issues, and contemporary ethical dilemmas relevant to IDF officers during active missions.

An Outbreak of Microsporum canis infection at a military base associated with stray cat exposure and person-to-person transmission

Tinea corporis caused by Microsporum canis is usually associated with exposure to animals, but outbreaks with anthropophilic transmission were described. A large outbreak in a military base was investigated. We investigated the outbreaks source and risk factors for infection in order to contain and eliminate it. All staff‐members at the base were interviewed and examined. A case‐control analysis of symptomatic patients was used to elucidate risk factors. Stray cats were captured and sampled. M. canis isolated from skin and fur specimens of patients and cats were genotyped by microsatellite sequencing. Fifty‐three of 502 staff‐members were symptomatic. Logistic regression showed risk associated with female gender, cat contact at base and performance of guarding duty. Multiple stray cats were found at the base. M. canis isolates from 4 cats and 4 patients had an identical genotype, while 2 patients had different genotypes. We describe the largest M. canis outbreak reported until now. Epidemiological and phylogenetic tools were used to investigate the source of the outbreak. Multiple exposures to stray cats caused infection of mainly young female soldiers performing guarding duty. Other persons were infected by person‐to‐person transmission. These findings aided in the termination of the outbreak.