Failure to Detect Leishmania in the Blood of Patients with Old-World Cutaneous Leishmaniasis: Implications for Blood Donation.

Cutaneous leishmaniasis (CL) is endemic in Israel, caused mainly by Leishmania major (L. major) and L. tropica. In addition, returning travelers import another leishmanial species such as L. braziliensis. Although we are dealing with a skin disease, the blood bank in Israel does not accept blood donations from people infected with CL in cases of multiple lesions due to the possibility of transfusion. Our purpose was to investigate the prevalence of Leishmania in the blood of patients with active or previous CL. This pilot study screened patients with active or previous CL for parasites in their blood. All patients were infected in Israel or were returning travelers with leishmaniasis acquired in Latin America. Patients were seen at the Sheba Medical Center. In addition, patients were seen at their homes in L. tropica and L. major endemic regions in Israel. Blood samples were taken from each patient for culture and polymerase chain reaction (PCR). Altogether 62 blood samples were examined (L. tropica = 26, L. major = 33, and L. braziliensis = 3). Twenty-seven patients had an active disease and 35 were recovered. All blood cultures and PCR were negative for parasites except one blood sample that was PCR positive for L. braziliensis. The findings of our study, although a small sample, suggest that people with active or recent CL caused by L. major and L. tropica, do not harbor parasites in their blood. Thus, their exclusion from blood donation should be revisited. Further studies are needed with larger sample size and highly sensitive tests.

Gender and Cutaneous Leishmaniasis in Israel.

Leishmaniasis is estimated to be more common in males than in females. Our purpose was to evaluate differences in preponderance in relation to sex and gender across cutaneous and mucocutaneous leishmaniasis in Israel. An observational study was performed, including cases of endemic CL (cutaneous leishmaniasis) in Israel, and imported MCL (mucocutaneous leishmaniasis). CL is a notifiable disease and is supposed to be reported to the Ministry of Health (MOH). The MOH database shows that males as more likely to be infected by leishmania, with an incidence of 5/100,000 in males vs. 3.5/100,000 in females. However, while conducting a demographic house-to-house survey in several locations in Israel where CL is highly endemic, among 608 people who were screened only 49% were males in Leishmania major (L. major) endemic regions and 41% were males in Leishmania tropica (L. tropica) endemic regions, while among 165 cases of imported New-World cutaneous leishmaniasis in Israeli travelers freturning from abroad, 142 (86%) were males. It may be postulated that there is no real gender difference in leishmanial infection, but, perhaps, infections are more commonly seen in men because of referral/reported bias, due to more risk-taking behaviors by men or, perhaps, men are less likely to strictly adhere to recommended preventive measures and thus increase their risk of contracting the disease.

Lessons from intensified surveillance of viral hepatitis A, Israel, 2017 and 2018.

IntroductionUniversal vaccination of toddlers has led to very low hepatitis A (HAV) endemicity in Israel. However, sporadic outbreaks still occur, necessitating better surveillance.AimTo implement a comprehensive HAV surveillance programme.MethodsIn 2017 and 2018, sera from suspected HAV cases that tested positive for anti-HAV IgM antibodies were transferred to the Central Virology Laboratory (CVL) for molecular confirmation and genotyping. Sewage samples were collected in Israel and Palestine* and were molecularly analysed. All molecular (CVL), epidemiological (District Health Offices and Epidemiological Division) and clinical (treating physicians) data were combined and concordantly assessed.ResultsOverall, 146 cases (78 in 2017 and 68 in 2018, median age 34 years, 102 male) and 240 sewage samples were studied. Most cases (96%) were unvaccinated. In 2017, 89% of cases were male, 45% of whom were men who have sex with men (MSM). In 2018, 49% were male, but only 3% of them were MSM (p < 0.01). In 2017, 82% of cases and 63% of sewage samples were genotype 1A, phylogenetically associated with a global MSM-HAV outbreak. In 2018, 80% of cases and 71% of sewage samples were genotype 1B, related to the endemic strain previously identified in Israel and Palestine*. Environmental analysis revealed clustering of sewage and cases' sequences, and country-wide circulation of HAV.ConclusionsMolecular confirmation of HAV infection in cases and analysis of environmental samples, combined with clinical and epidemiological investigation, may improve HAV surveillance. Sequence-based typing of both clinical and sewage-derived samples could assist in understanding viral circulation.

A Pilot Study to Reduce Central Line-Associated Bloodstream Infections in Children From Extremely Low-Income Settings With Intestinal Failure-Meeting the Challenge.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are major sources of morbidity, death, and healthcare costs in patients who receive home parenteral nutrition (HPN). The majority of HPN-dependent children in southern Israel reside in poor communities with substandard living conditions, which creates significant challenges for the safe provision of HPN. We developed a pilot intervention that aimed to reduce the rates of CLABSI and central venous catheter (CVC) replacements in this vulnerable population in our region. METHODS: Between 2012 and 2014, all HPN-dependent children with intestinal failure who were treated in our center, received HPN through a Hickman catheter, and experienced at least 1 previous CLABSI episode participated in the intervention. The intervention included home visits to assess the caregivers' CVC-handling technique, instillation of prophylactic ethanol lock solution, and the convening of regular multidisciplinary staff debriefings. We calculated CLABSI and CVC-replacement rates before and after the intervention. RESULTS: Eight patients who served as their own historical controls were included in the intervention (total of 2544 catheter-days during the intervention period). The mean CLABSI rate decreased from 9.62 to 0.79 CLABSI episodes per 1000 catheter-days; the CVC-replacement rate decreased from 2.5 to 1.2 replacements per 1000 catheter-days in the preintervention and intervention periods respectively. The median hospital length of stay and individual monthly cost of medical care decreased compared to those found in the preintervention period. CONCLUSIONS: The results of this study offer a proof of concept for a strategy to reduce CLABSI rates in pediatric patients who reside in remote and low-resource environments and are undergoing HPN.

Relapsing Fever: Diagnosis Thanks to a Vigilant Hematology Laboratory.

Three cases of relapsing fever from southern Israel were diagnosed promptly thanks to vigilance of the hematology laboratory technicians. In this region of Israel, patients presenting with prolonged fever and leukopenia without localizing symptoms are generally suspected of having brucellosis or a rickettsial disease. Pediatric patients with prolonged fever, cytopenias, and negative aforementioned serologies are often hospitalized for further work-up. Because of the policy of performing a manual blood smear when results of the automated blood count demonstrate severe anemia and abnormal platelet and/or white blood cell counts, a diagnosis of tick-borne relapsing fever was confirmed and promptly relayed to the physician. This routine prevented unnecessary examinations and hospitalization days and provided important information to regional epidemiology and public health authorities.

NS1 antigen testing for the diagnosis of dengue in returned Israeli travelers.

Antigen testing with NS1 provides rapid diagnosis of dengue in endemic regions during the febrile phase of illness before appearance of IgM in serum. This study aimed to determine the diagnostic accuracy of NS1 antigen testing in travelers presenting with febrile illness and serologically confirmed dengue infection, upon return from dengue endemic countries to Israel, a region endemic for West Nile virus (WNV). Cases were sera obtained from febrile returning travelers with positive dengue-IgM antibodies. Sera of non-travelers with confirmed WNV disease and sera of returning travelers with confirmed non-dengue febrile illnesses were used as controls. All sera were tested for NS1 antigen using the Panbio Dengue Early ELISA assay within 21 days of symptoms. Demographic data, travel destination, and interval between disease onset and testing were retrieved from patient files. Fifty-eight sera from 40 dengue-infected travelers, 26 sera from 26 WNV- infected patients, and 15 sera of returning travelers with non-dengue febrile illness were tested. Sensitivity of NS1 testing in dengue patients was 87% during the first 3 days of symptoms and declined to about 70% after 12 days. No cases tested positive for NS1 after day 12. Specificity was 92% for the entire testing period. The NS1 Panbio assay is sensitive for the detection of dengue viral infection in returning travelers during the febrile phase of illness, and is highly specific in a region where WNV co-circulates.

Hepatitis B and C reactivation with tumor necrosis factor inhibitors: synopsis and interpretation of screening and prophylaxis recommendations.

Information on reactivation of chronic viral hepatitis infection in patients who are candidates for tumor necrosis factor alpha inhibitors (TNFi) is in a constant state of flux. We retrieved the most updated guidelines (in English) of prominent rheumatological and gastroenterological professional socienties for the mangement of chronic hepatitis B (HBV) and hepatitis C virus (HCV) infection in the context of treatment with TNFi. Subsequently, the major areas of uncertainty and absence of consensus in the guidelines were located and a secondary search for additional studies addressing those areas was performed. Based on our search we formulated a personal interpretation applicable to health care settings with virological laboratories capable of performing viral load measurements, and health systems that can support use of potent nucleoside/tide analogues in well-defined patient populations.

Proactive approach to containment of enterovirus infection in the nursery.

Administration of prophylactic intravenous immunoglobulins to contacts of infants actively shedding enterovirus during a hospital nursery outbreak may attenuate severity of disease in those contacts and aid in containment of the outbreak. Four cases of neonatal enteroviral disease were treated in our hospital nursery in July and August 2011; 3 were presumed or proven vertical transmission cases and 1 was a presumed horizontal transmission. We aimed to prevent development of severe illness in contacts of affected neonates following a ministry of health advisory during the summer of 2011 warning of increased neonatal enteroviral morbidity and mortality in Israel. Strict infection control measures were implemented, including meticulous decontamination of the nursery environment and administration of intravenous immunoglobulin prophylaxis to contacts. No further horizontal transmission occurred after infection control interventions. Immunoglobulin prophylaxis to control enteroviral infection in the nursery should be considered as an auxiliary infection control intervention during a nursery outbreak.

Serotypeº1 [corrected] childhood invasive pneumococcal disease has unique characteristics compared to disease caused by other streptococcus pneumoniae serotypes.

BACKGROUND: We aimed to determine whether serotype 1 (SP1) invasive pneumococcal disease (IPD) can be distinguished by demographic, clinical and laboratory characteristics from IPD caused by the other most common serotypes (MCS) in our region: 5, 14, 6A, 6B, 19A, 19F, 23F. METHODS: Data for all IPD episodes in children <18 years old treated at the Soroka University Medical Center during 2000 to 2009 were retrospectively retrieved. Episodes caused by SP1-IPD were compared with those caused by MCS-IPD (both grouped and individual serotypes). Analyses were adjusted for age and ethnicity. RESULTS: Ninety-four SP1-IPD and 250 MCS-IPD episodes were documented. SP1-IPD cases were older (68.3 ± 52.6 months versus 30.4 ± 39.2 months; P < 0.001) and more likely to be found in Bedouin children than MCS-IPD (87.5% versus 58.6%; P < 0.001). SP1 was less frequently isolated from patients with underlying disease than MCS (14.9% versus 31.6 %; P < 0.001; relative risk 0.15 [95% confidence interval: 0.07-0.32]). SP1 was more often associated with bacteremic pneumonia and primary peritonitis than MCS (66% versus 38.4% and 7.4% versus 0.8%, respectively; P < 0.001); the proportion of bacteremia without focus was higher in MCS-IPD (32.4% versus 12.5%; P < 0.001). There were no differences in hospitalization and mortality rates (70.2% versus 68.0% [P = 0.22] and 4.3% versus 5.6% [P = 0.26], respectively). CONCLUSIONS: SP1 was found less frequently than MCS in children with underlying diseases, but it was more frequent in older and Bedouin children with IPD. SP1 was more frequently associated with bacteremic pneumonia and primary peritonitis than MCS grouped.

Unusual presentations of pediatric neurobrucellosis.

Neurobrucellosis is an uncommon complication of pediatric brucellosis. Acute meningitis and encephalitis are the most common clinical manifestations, however symptoms may be protean and diagnosis requires a high index of suspicion in patients from endemic areas. Diagnosis is often based on neurological symptoms, serology, and suggestive brain imaging because cerebrospinal fluid culture yields are low. Two cases of pediatric neurobrucellosis with unusual clinical and radiologic findings are presented.

Repeated tuberculin skin testing following therapy with TNF-alpha inhibitors.

To determine the rate of true tuberculin skin test (TST) response in a cohort of patients with rheumatic disease treated with tumor necrosis factor inhibitors (TNFi). The study population included consecutive patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) treated with TNFi for at least 3 months. Patients with a positive TST at screening who began Tb prophylaxis before the beginning of TNFi therapy were excluded. All patients underwent a second TST. True TST response was defined as an increase of 6 mm of induration between the screening test and the second test. Forty patients (12 men and 28 women) were included. Mean age was 51.2 years. Of them, 27 (67.5%) had RA, eight (20%) had PsA, and five patients (12.5%) had AS. At pre-treatment TST, 15 patients had a TST > or = 5 mm. A significantly higher percent of patients with TST > or = 5 mm was seen among men compared with women (75% vs. 21%, p = 0.012) and patients with PsA compared with patients with RA (75% vs. 22%, p = 0.014). At the second test, eight (20%) had an increase of 6 mm between readings with four having an increase of 10 mm or more. Four patients received infliximab and the other four were treated with etanercept. Seven of these eight patients had RA and one was a patient with PsA. Patients with true TST response were significantly older and non-smokers with elevated sedimentation rate and a higher rate of anemia. Nationality, comorbid conditions, treatment with immunosuppressives, and BCG vaccination status had no significant influence on the TST response. Serial TST testing in patients receiving TNFi is indicated to identify patients with reactivation of latent tuberculosis infection or those exposed to mycobacterium.