Ziva Amitai

A Large Q Fever Outbreak in an Urban School in Central Israel

BACKGROUND. On 28 June 2005, numerous cases of febrile illness were reported among 322 students and employees of a boarding high school located in an urban area in central Israel. Subsequent investigation identified a large outbreak of Q fever which started 2 weeks earlier. We describe the investigation of this outbreak and its possible implications. METHODS. We conducted a case-control study to identify risk factors for Q fever disease. Environmental sampling was conducted to identify the source and the mode of transmission of Coxiella burnetii, the infectious agent. RESULTS. Of 303 individuals, 187 (62%) reported being ill between 15 June and 13 July 2005. Serological evidence for C. burnetii infection was evident in 144 (88%) of the 164 tested individuals. Being a student, dining regularly at the school dining room, and boarding at school during a June religious holiday and the preceding weekend were all significant risk factors for contracting Q fever. C. burnetii DNA was detected using polymerase chain reaction on samples from the school dining rooms air conditioning system, supporting contribution of the air conditioning system to the aerosol transmission of the infectious agent. CONCLUSIONS. We report a large outbreak of Q fever in an urban school, possibly transmitted through an air conditioning system. A high level of suspicion for C. burnetii infection should be maintained when investigating point source outbreaks of influenza-like disease, especially outside the influenza season.

An outbreak of Phialemonium infective endocarditis linked to intracavernous penile injections for the treatment of impotence.

BACKGROUND In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous. METHODS We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. RESULTS We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans. CONCLUSIONS P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes.

Ongoing hepatitis A among men who have sex with men (MSM) linked to outbreaks in Europe in Tel Aviv area, Israel, December 2016 – June 2017

Between December 2016 and June 2017, 19 Hepatitis A virus (HAV)-positive cases, 17 of which were among men who have sex with men (MSM) were identified in the Tel Aviv area. Seven of the 15 sewage samples collected between January and June 2017 were also HAV-positive. All sequences clustered with two of the three strains identified in the current European HAV outbreak. We demonstrate that despite an efficient vaccination programme, HAV can still be transmitted to an unvaccinated high-risk population.

Outbreak of adenovirus type 55 infection in Israel

BACKGROUND Different types of adenoviruses are associated with diverse diseases and with varied disease severity. Adenovirus 55 could be associated with severe respiratory infections. OBJECTIVES Here, we report on an adenovirus 55 outbreak in two psychiatric institutions in Israel. The objective of this study was to investigate the adenovirus 55 outbreak. STUDY DESIGN We studied the clinical parameters of the patients and sequencing analysis of certain parts of the virus gene was performed. RESULTS We identified the first patient who developed symptoms (the index case) and we showed that while both patients and staff members of the institutions were infected, the disease in the psychiatric patients was more severe. We attributed these differences to their mental and underlying health conditions. CONCLUSIONS It is important to monitor for adenovirus infection in the community, especially in mental health institutions to allow appropriate medical care.

Possible recurrent pandemic (H1N1) 2009 infection, Israel.

To the Editor: We report 2 cases of possible recurrent laboratory-confirmed infection with pandemic (H1N1) 2009 virus in Israel. Patient 1, a 24-year-old man, had Noonan syndrome (1,2). He was hospitalized on August 10, 2009, because of high-grade fever and cough. At admission, a nasopharyngeal specimen was collected for pandemic (H1N1) 2009 virus real-time reverse transcription–PCR (RT-PCR) (ABI 7500; Applied Biosystems, Foster City, CA, USA) for the pandemic hemagglutinin gene; a validated in-house protocol developed at Israel Central Virology Laboratory was used, as previously described (3). Briefly, the in-house assay was validated against the assay for pandemic (H1N1) 2009 virus developed by the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA). The in-house assay was as sensitive as the CDC assay; however, the in-house primers and probes were more specific for detecting pandemic (H1N1) 2009 virus with 105% amplification efficiency of viral RNA that was logarithmically serially diluted. In addition, of 100 samples tested side by side with the in-house and CDC assays, 75 samples were positive by both assays, and 25 were negative by both assays; thus, the sensitivity and specificity of the in-house assay were 100%. The patient was not treated with neuraminidase inhibitors and did not require supportive treatment; after 1 day of hospitalization, he was discharged with a diagnosis of upper respiratory tract infection. The laboratory subsequently reported the RT-PCR as positive for pandemic (H1N1) 2009 virus. On November 22, the man was hospitalized again for dyspnea and fever. The RT-PCR result from a nasopharyngeal sample collected at admission was positive. Hemagglutination-inhibition assay demonstrated a high titer (320) of serum antibody against pandemic (H1N1) 2009 virus in a blood sample taken at admission. The patient took oseltamivir for 5 days, and his condition markedly improved. Result of a repeat RT-PCR at discharge was negative. An identical neuraminidase gene sequence was detected during both illness episodes (August and November). The specimens were also tested with an experimental RT-PCR assay for rapid detection of the oseltamivir resistance mutation H275Y on the pandemic neuraminidase gene (4). For specimens collected during both episodes, the virus was oseltamivir sensitive. Patient 2, a 13.5-year-old boy, had severe cerebral palsy. On July 27, 2009, high-grade fever with dyspnea developed. He was treated as an outpatient for 5 days with oseltamivir and clinically improved. However, on August 11, he had fever with respiratory distress and was hospitalized. RT-PCR for pandemic (H1N1) 2009 virus was positive on August 14. A second course of oseltamivir was administered for 10 days with the dosage adjusted for age and doubled from that of the previous regimen. Further testing with the experimental rapid RT-PCR indicated the viral strain had the oseltamivir resistance mutation. On September 14, RT-PCR was negative. On December 11, the boy was again hospitalized because of respiratory distress and high-grade fever. On December 14, RT-PCR was positive for pandemic (H1N1) 2009 virus, and a 5-day regimen of oseltamivir was started. Another specimen taken the same day was negative. A high serum antibody titer (320) to pandemic (H1N1) 2009 virus was measured by hemagglutination-inhibition assay on December 16; no oseltamivir resistance mutation was found. Additional laboratory testing included a complete panel for respiratory viruses, which was negative for human metapneumovirus; respiratory syncytial virus; adenovirus; seasonal influenza virus types A and B; and parainfluenza virus types 1, 2, and 3. These 2 cases of possible recurrent pandemic (H1N1) 2009 infection demonstrated a wide interval between illness episodes. Neither patient had accompanying immunodeficiency, and both had antibody titers far beyond the accepted seroprotective threshold for influenza (5), albeit ineffective. These titers probably resulted from primary infection rather than from subclinical exposure, which manifests itself as a lower titer by order of magnitude (6,7). Virus clearance was not laboratory confirmed for patient 1 after the first episode because no samples were taken after hospital discharge. Patient 2 had both positive and negative RT-PCRs for pandemic (H1N1) 2009 virus (Table) from samples collected the same day during the second hospitalization, which also may disprove reinfection. The positive result could be explained by laboratory contamination during the RT-PCR processing that indicated a false-positive result. However, contamination is unlikely because each run of the RT-PCR was routinely accompanied by runs of negative controls (that contain water) to rule out such contamination. Nonanalytic factors such as specimen misidentification also are unlikely because the central virology laboratory, which is the national reference center, has an ISO-9000 qualification from the Standards Institution of Israel (www.sii.org.il/20-en/SII_EN.aspx). Furthermore, no other respiratory virus was found by laboratory testing at that time. The patient was infected with an oseltamivir-resistant pandemic (H1N1) 2009 virus during the first illness episode and with an oseltamivir-sensitive virus during the second episode and had 2 RT-PCRs with negative results between the episodes. Table Real-time RT-PCR for pandemic (H1N1) 2009 virus and results of experimental assay* for oseltamivir resistance mutation H275Y, Israel, 2009† The novel pandemic influenza virus may be able to reinfect certain chronically ill persons. Caregivers should be aware of this trait when considering the differential diagnosis of influenza-like illness in a patient with a documented, and even treated, pandemic (H1N1) 2009 infection.

Tinea capitis outbreak in a paediatric refugee population, Tel Aviv, Israel

Tinea capitis, also known as scalp ringworm, is a condition that affects mainly prepubertal children worldwide and is usually caused by members of the genera Microsporum and Trichophyton (Weitzman I et al., Clin Microbiol Rev 1995; 8: 240–59). Tinea capitis was the major fungal infection in Israel from the beginning of the 20th century until the end of the 1950s. Its predominant agent was T. violaceum and it was endemic with occasional outbreaks until the introduction of griseofulvin in 1958. Following that, a continuous decline in the prevalence of tinea capitis was observed until the introduction of M. canis to Israel in 1975. Since then, M. canis has become the main aetiologic pathogen of tinea capitis in Israel (Evron R et al., Mycopathologia 1985; 90: 113–20). During 2009, an outbreak of tinea capitis occurred among children from the African refugee community of Tel Aviv city.

Patients with Pandemic (H1N1) 2009 in Intensive Care Units, Israel

To the Editor: We report results of an active surveillance system established by the Tel Aviv District Health Office in Israel. This surveillance system monitors the daily status of patients with laboratory-confirmed pandemic (H1N1) 2009 virus infection in each of the district’s intensive care units (ICUs), including pediatric ICUs. Follow-up is maintained by daily phone conversations with medical staff until disease outcome is concluded by discharge, transfer to a long-term rehabilitation facility, or death. Medical records, as well as daily laboratory reports, are collected to confirm or to rule out pandemic (H1N1) 2009 infection. During July 10–October 10, 2009, our prospective cohort included 17 patients with pandemic (H1N1) 2009 laboratory-confirmed infection who were residents of the district; 12 (70.6%) were male patients. The median age was 44 years (interquartile range 13–72 years). By October 10, 2009, six patients had been discharged, 7 had died, 2 had been transferred to long-term rehabilitation facilities, and 2 remained hospitalized. Twelve (70.6%) patients had an underlying medical condition, mainly chronic lung disease (6 patients) or chronic cardiovascular disease (5 patients). Two patients were morbidly obese (body mass index >35), and 1 patient was pregnant. Additionally, 3 patients (17.6%) were infected while hospitalized. Thirteen patients (76.5%) had acute respiratory distress syndrome caused by diffuse viral pneumonitis. Other notable manifestations were acute renal failure (6 patients), sepsis/septic shock (5 patients), and neurologic complications such as Guillain-Barre syndrome, encephalitis, and seizures (3 patients). Documented nosocomial sepsis, often of multiple gram-negative bacteria (9 patients), was the most frequent complication during the course of the disease. Other frequent characteristics were the use of high positive end-expiratory pressure during mechanical ventilation (4 patients) and the need for tracheostomy (5 patients). Average time from disease onset to hospital admission was 3 days. Time from hospital admission to ICU admission for those patients who died was longer than for those who survived, with a median of 2 days compared with 0.5 day, respectively, albeit not significant (p = 0.26). Average hospitalization was 23.4 days; average length of stay in the ICU was 16.7 days (71.4% of the average hospitalization time). As mentioned previously, 7 patients (41.2%) died; 5 (71.4%) were male, similar to their cohort’s proportion. One significant difference (p = 0.02) was found between the age of survivors (mean 26.0 years, 95% confidence interval 7.6–44.3) and the age of nonsurvivors (mean 59.3 years, 95% confidence interval 39.6–79.0). The most prominent case–fatality rate was for elderly patients, >65 years of age (3 of 4 patients) followed by patients between 20 and 64 years of age (4 of 9 patients); these subgroups constituted 23.5% and 52.9% of the cohort, respectively. Estimated incidence rate was 13.8 patients and 5.7 deaths in ICUs per million residents in the Tel Aviv district. Again, the elderly subgroup was dominant, with the highest estimated rate of illness (23.1 per million residents) and death rate (17.3 per million residents). The denominator of these rates was calculated from the population data published by the Israeli Central Bureau of Statistics for 2007 and 2008. Upon that basis, the population data for the end of the third quarter of 2009 was estimated. During the described surveillance period, 5.7% of ICU beds in the district were, on average, continuously occupied by patients infected with pandemic (H1N1) 2009. The occupancy peak was 6.5 of 53.8 standardized ICU beds (12.1%) per million residents during the week ending August 28, 2009 (Figure). Figure Number of intensive care unit (ICU) beds occupied by patients with pandemic (H1N1) 2009 infection in district ICUs during the described surveillance period, Tel Aviv, Israel. During this period, 5.7% of ICU beds, on average, were continuously occupied ... In conclusion, our analysis of patients having the most severe pandemic (H1N1) 2009 infection indicates a need for prolonged periods of hospitalizations, especially in ICUs, for young adults and elderly patients. Death or prolonged adverse complications were frequent outcomes. We found that the impact of patients with pandemic (H1N1) 2009 on the ICUs in our district during the summer wave was surprisingly similar in length and intensity to the impact that was recently reported in Australia and New Zealand during the winter wave (1). The maximum number of ICU beds occupied per million residents, reported for all regions of Australia and New Zealand combined, was 7.4 during the week ending July 27, 2009 (vs. 6.5 as described above). We also found that the mean age of those who died was older than that in previous reports (2–6).This finding may present a need for policymakers to reconsider current vaccination priorities (7) while facing the winter wave of influenza in the Northern Hemisphere.

Recurrent Outbreak of Pandemic (H1N1) 2009 Virus Infection in a Pediatric Long-Term Care Facility and the Adjacent School

1. Bush LM, Kaye D. Catheter-associated urinary tract infection IDSA guidelines: why the levofloxacin? Clin Infect Dis 2010; 51(4):479–480 (in this issue). 2. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:625–663. 3. Peterson J, Kaul S, Khashab M, et al. A doubleblind, randomized comparison of levofloxacin 750 mg once daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71:17–22.