Dan Engelhard

Publications of Dan Engelhard

• Functional STAT3 deficiency compromises the generation of human T follicular helper cells.

  Authors: Cindy S Ma, Danielle T Avery, Anna Chan, Marcel Batten, Jacinta Bustamante, Stephanie Boisson-Dupuis, Peter D Arkwright, Alexandra Y Kreins, Diana Averbuch, Dan Engelhard [......] Sharon Choo, Joanne M Smart, Jane Peake, Melanie Wong, Paul Gray, Matthew C Cook, David A Fulcher, Jean-Laurent Casanova, Elissa K Deenick, Stuart G Tangye

  Blood. 03/2012;

  T follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify theT follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify the molecular requirements for Tfh cell development and function. We previously found that IL-12 mediates the differentiation of human CD4(+) T cells to the Tfh lineage, since IL-12 induces naïve human CD4(+) T cells to acquire expression of IL-21, BCL6, ICOS and CXCR5, which typify Tfh cells. We have now examined CD4(+) T cells from patients deficient in IL-12Rβ1, TYK2, STAT1 and STAT3 to further explore the pathways involved in human Tfh cell differentiation. While STAT1 was dispensable, mutations in IL12RB1, TYK2 or STAT3 compromised IL-12-induced expression of IL-21 by human CD4+ T cells. Defective expression of IL-21 by STAT3-deficient CD4(+) T cells resulted in diminished B-cell helper activity in vitro. Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell generation in vivo, evidenced by decreased circulating CD4(+)CXCR5(+)CD45RA(-) T cells. These results highlight the non-redundant role of STAT3 in human Tfh cell differentiation and suggest that defective Tfh cell development and/or function contributes to the humoral defects observed in STAT3-deficient patients.

• Severe influenza A (H1N1): the course of imaging findings.

  Authors: Dorith Shaham, Naama R Bogot, Galit Aviram, Ludmila Guralnik, Sivan Lieberman, Laurian Copel, Jacob Sosna, Allon E Moses, Itamar Grotto, Dan Engelhard

  The Israel Medical Association journal : IMAJ. 10/2011; 13(10):591-6.

  An outbreak of respiratory illness caused by a novel swine-origin influenza virus (influenza A/H1N1 2009) that began in Mexico was declared a global pandemic by the World Health Organization in JuneAn outbreak of respiratory illness caused by a novel swine-origin influenza virus (influenza A/H1N1 2009) that began in Mexico was declared a global pandemic by the World Health Organization in June 2009. The pandemic affected many countries, including Israel. To compare the course of chest radiographic and computed tomography findings in patients who survived and those who died following admission to the intensive care unit (ICU) or intubation due to severe laboratory-confirmed swine-origin influenza A/H1N1 2009. We retrospectively reviewed the patient records (267 radiographs, 8 CTs) of 22 patients (10 males, 12 females) aged 3.5-66 years (median 34) with confirmed influenza A/ H1N1 2009, admitted to the ICU and/or intubated in five major Israeli medical centers during the period July-November 2009. We recorded demographic, clinical, and imaging findings--including pattern of opacification, extent, laterality, distribution, zone of findings, and presence/absence of nodular opacities--at initial radiography and during the course of disease, and compared the findings of survivors and non-survivors. Statistical significance was calculated using the Wilcoxon (continuous variables) and Fisher exact tests. The most common findings on the initial chest radiography were airspace opacities, which were multifocal in 17 patients (77%) and bilateral in 16 (73%), and located in the lower or lower and middle lung zones in 19 patients (86%). Large airspace nodules with indistinct margins were seen in 8 patients (36%). Twelve patients survived, 10 died. Patients who died had multiple background illnesses and were significantly older than survivors (P = 0.006). Radiologic findings for the two groups were not significantly different. Airspace opacities, often with nodular appearance, were the most common findings among patients with severe influenza A/H1N1 2009. The course of radiologic findings was similar in patients with severe influenza A/ H1N1 2009 who survived and those who died.

• Increased extent of and risk factors for pandemic (H1N1) 2009 and seasonal influenza among children, Israel.

  Authors: Dan Engelhard, Michal Bromberg, Diana Averbuch, Ariel Tenenbaum, Daniele Goldmann, Marina Kunin, Einat Shmueli, Ido Yatsiv, Michael Weintraub, Michal Mandelboim, Nurith Strauss-Liviatan, Emilia Anis, Ella Mendelson, Tamy Shohat, Dana G Wolf, Mervyn Shapiro, Itamar Grotto

  Emerging infectious diseases. 09/2011; 17(9):1740-3.

  During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. ChildrenDuring the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.

• Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis.

  Authors: Luyan Liu, Satoshi Okada, Xiao-Fei Kong, Alexandra Y Kreins, Sophie Cypowyj, Avinash Abhyankar, Julie Toubiana, Yuval Itan, Magali Audry, Patrick Nitschke [......] Matias Oleastro, Amos Etzioni, Claudia Traidl-Hoffmann, Ellen D Renner, Laurent Abel, Capucine Picard, László Maródi, Stéphanie Boisson-Dupuis, Anne Puel, Jean-Laurent Casanova

  The Journal of experimental medicine. 08/2011; 208(8):1635-48.

  Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, weChronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.

• An outbreak of adenovirus type 7 in a residential facility for severely disabled children.

  Authors: Hammam Ghanaiem, Diana Averbuch, Benjamin Z Koplewitz, Ido Yatsiv, Jackues Braun, Natali Dehtyar, Dana G Wolf, Michal Mandelboim, Dan Engelhard

  The Pediatric infectious disease journal. 06/2011; 30(11):948-52.

  Adenoviruses cause a variety of clinical symptoms, involving the respiratory, gastrointestinal, urogenital, and neurologic systems. Only a few of the 55 known serotypes of adenovirus that affectAdenoviruses cause a variety of clinical symptoms, involving the respiratory, gastrointestinal, urogenital, and neurologic systems. Only a few of the 55 known serotypes of adenovirus that affect humans can cause outbreaks of respiratory tract infection. To describe the characteristics and clinical manifestations of severe respiratory disease contracted by 8 physically and cognitively disabled children during a very short outbreak of adenovirus serotype 7 infection in a residential facility. The clinical, imaging, and laboratory findings of the patients who were hospitalized with severe respiratory symptoms were retrospectively reviewed. Molecular typing of the adenovirus was performed. During 10 days in February 2010, 8 severely disabled children, 9 months to 5 years of age (median 22.5 months), from the same residential facility, were hospitalized due to severe acute respiratory disease with hypoxemia. Four of them (50%) needed mechanical ventilation for 2 to 8 days and one developed multisystem failure, including acute renal failure. Adenovirus serotype 7 was detected in the respiratory specimens of all 8 children. Two patients were treated with intravenous cidofovir. All 8 patients survived and were discharged after hospitalization of 6 to 15 (median: 11.5) days. The epidemiologic investigation revealed that all the 8 affected children shared a playroom and a caregiver worked with them while suffering fever, sore throat, and conjunctivitis before the onset of the outbreak. Adenovirus type 7 may cause short outbreaks of infection in institutions, causing children to develop life-threatening disease. Early detection of pathogens causing respiratory infections in institutions, isolation, and other preventive precautions are advocated. Moreover, vaccination of health care providers in institutions with the currently available live, oral adenovirus vaccine for types 4 and 7 should be considered.

• Macrolide resistance in Mycoplasma pneumoniae, Israel, 2010.

  Authors: Diana Averbuch, Carlos Hidalgo-Grass, Allon E Moses, Dan Engelhard, Ran Nir-Paz

  Emerging infectious diseases. 06/2011; 17(6):1079-82.

  Macrolide resistance in Mycoplasma pneumoniae is often found in Asia but is rare elsewhere. We report the emergence of macrolide-resistant M. pneumoniae in Israel and the in vivo evolution of suchMacrolide resistance in Mycoplasma pneumoniae is often found in Asia but is rare elsewhere. We report the emergence of macrolide-resistant M. pneumoniae in Israel and the in vivo evolution of such resistance during the treatment of a 6-year-old boy with pneumonia.

• Congenital cytomegalovirus infection and Wiskott-Aldrich syndrome successfully treated with unrelated cord blood transplantation.

  Authors: Yotam Almagor, Shoshana Revel-Vilk, Diana Averbuch, Hadas Mechoulam, Dan Engelhard, Igor B Resnick, Michael Weintraub, Polina Stepensky

  Pediatric blood & cancer. 05/2011; 57(4):681-3.

  We report a successful umbilical cord blood transplantation (UCBT) in an 8-month male with Wiskott-Aldrich syndrome (WAS) and congenital cytomegalovirus (CMV) infection. The child presented at 3We report a successful umbilical cord blood transplantation (UCBT) in an 8-month male with Wiskott-Aldrich syndrome (WAS) and congenital cytomegalovirus (CMV) infection. The child presented at 3 months of age with symptomatic thrombocytopenia and CMV infection. Despite appropriate antiviral treatment no rise in the platelet count was observed. Genetic analysis confirmed the diagnosis of WAS. The clinical course was complicated by severe CMV retinitis with bilateral retinal hemorrhages and renal vasculitis. He underwent unrelated UCBT resulting in a rapid resolution of autoimmunity and thrombocytopenia.

• Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients.

  Authors: Per Ljungman, Rafael de la Camara, Lena Perez-Bercoff, Manuel Abecasis, Jose Bartolo Nieto Campuzano, M Jimena Cannata-Ortiz, Catherine Cordonnier, Hermann Einsele, Marta Gonzalez-Vicent, Ildefonso Espigado, Jörg Halter, Rodrigo Martino, Bilal Mohty, Gülsan Sucak, Andrew J Ullmann, Lourdes Vázquez, Katherine N Ward, Dan Engelhard

  Haematologica. 05/2011; 96(8):1231-5.

  During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cellDuring 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; 1.33-4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.

• The humoral immune response of hematopoietic stem cell transplantation recipients to AS03-adjuvanted A/California/7/2009 (H1N1)v-like virus vaccine during the 2009 pandemic.

  Authors: Dan Engelhard, Zichria Zakay-Rones, Michael Y Shapira, Igor Resnick, Diana Averbuch, Sigal Grisariu, Lillian Dray, Esther Djian, Nurith Strauss-Liviatan, Itamar Grotto, Dana G Wolf, Reuven Or

  Vaccine. 02/2011; 29(9):1777-82.

  We evaluated the formation of hemagglutination-inhibition (HI) antibodies in response to vaccination of 55 allogeneic and 23 autologous hematopoietic stem cell transplantation (HSCT) recipients withWe evaluated the formation of hemagglutination-inhibition (HI) antibodies in response to vaccination of 55 allogeneic and 23 autologous hematopoietic stem cell transplantation (HSCT) recipients with 3.75 μg inactivated influenza A/California/7/2009 (H1N1)v-like virus adjuvanted with AS03, given towards the end of the 2009 influenza pandemic. The 78 HSCT recipients, aged 11-72 (median 50) years, were vaccinated 1-290 (median 27) months post-HSCT. Of the 55 allogeneic HSCT recipients, 50.9% received reduced intensity conditioning, 74.5% had a sibling donor, 67.2% had active graft-versus-host disease and 43.6% were on steroid therapy. At baseline, 14/78 (17.9%) had HI titers ≥ 1:40. Blood samples of 77 patients were available post-1st vaccination; of these, 34 (44.2%) patients had HI titers ≥ 1:40. Blood samples of 43 patients were available post-2nd vaccination; of these, 21 (48.8%) had HI titers ≥ 1:40. There was a significant increase in HI titers ≥ 1:40 from baseline to both post-1st and 2nd vaccinations (p<0.001 each), and also from 1st to 2nd vaccination (p=0.008). In seronegative (HI titers <1:10) patients, whose sera were available before, after one dose, and after 2 doses of vaccine, seroconversion (to ≥ 1:40) occurred in 4/24 (16.7%) after 1-dose and in a total of 10/24 (41.7%) after 2-dose vaccination (p=0.031). Logistic regression analysis revealed that ≥ 1:40 HI titers were significantly associated with higher lymphocyte counts and higher HI baseline titers and, in allogeneic HSCT, with having a sibling donor and higher baseline titers. In conclusion, 2-dose vaccination with AS03-adjuvanted vaccine containing 3.75 μg antigen resulted in a statistically significant, yet limited, serological response. Therefore, additional precautions should be taken during influenza outbreaks.

• The clinical spectrum of patients with deficiency of Signal Transducer and Activator of Transcription-1.

  Authors: Diana Averbuch, Ariane Chapgier, Stéphanie Boisson-Dupuis, Jean-Laurent Casanova, Dan Engelhard

  The Pediatric infectious disease journal. 10/2010; 30(4):352-5.

  STAT-1 (Signal Transducer and Activator of Transcription-1) is a key signaling component of interferon gamma responses. We present long-term manifestations in siblings with a mutation in the STAT1STAT-1 (Signal Transducer and Activator of Transcription-1) is a key signaling component of interferon gamma responses. We present long-term manifestations in siblings with a mutation in the STAT1 gene, which include invasive salmonellosis, recurrent severe respiratory syncytial virus pneumonitis, and hepatosplenic mycobacterial disease, and we summarize all other reported cases with STAT-1 deficiency.

• Community-acquired oseltamivir-resistant pandemic (H1N1) 2009 in child, Israel.

  Authors: Zeev Zonis, Dan Engelhard, Musa Hindiyeh, Daniela Ram, Michal Mandelboim, Ella Mendelson, Daniel Glikman

  Emerging infectious diseases. 06/2010; 16(6):1045-6.

• Spreading the handwashing message: an alternative to traditional media campaigns.

  Authors: Laura Rosen, David Brody, David Zucker, Orly Manor, Marina Meier, Bruce Rosen, Eimi Lev, Dan Engelhard

  American journal of infection control. 04/2010; 38(7):562-4.

  Schools are a natural place from which to disseminate health messages to the community. Sending an entertaining handwashing video home with preschoolers as a component of a school-based programSchools are a natural place from which to disseminate health messages to the community. Sending an entertaining handwashing video home with preschoolers as a component of a school-based program yielded impressive degrees of penetration and reach among families; consequently, this strategy offers a promising alternative to traditional media campaigns.

• Development of oseltamivir resistance during oseltamivir therapy in a child with severe 2009 H1N1 influenza.

  Authors: Daniel Glikman, Zeev Zonis, Musa Hindiyeh, Musa Hindyieh, Daniela Ram, Michal Mandelboim, Ella Mendelson, Dan Engelhard

  The Pediatric infectious disease journal. 04/2010; 29(4):385-6.

• B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans.

  Authors: Danielle T Avery, Elissa K Deenick, Cindy S Ma, Santi Suryani, Nicholas Simpson, Gary Y Chew, Tyani D Chan, Umamainthan Palendira, Jacinta Bustamante, Stéphanie Boisson-Dupuis [......] Joachim Roesler, Peter D Arkwright, Pravin Hissaria, D Sean Riminton, Melanie Wong, Robert Brink, David A Fulcher, Jean-Laurent Casanova, Matthew C Cook, Stuart G Tangye

  The Journal of experimental medicine. 01/2010; 207(1):155-71.

  Engagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyteEngagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21-induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients.

• [The safety and immunogenicity of the vaccines against pandemic (H1N1) 2009 influenza].

  Authors: Itamar Grotto, Dan Engelhard

  Harefuah. 12/2009; 148(12):799-803, 857.

  The current pandemic (H1N1) 2009 influenza is spreading worldwide with a significant increase in morbidity and mortality noted in Israel, as well as in many other countries of the NorthernThe current pandemic (H1N1) 2009 influenza is spreading worldwide with a significant increase in morbidity and mortality noted in Israel, as well as in many other countries of the Northern Hemisphere. In an attempt to minimize severe morbidity and mortality, immunization projects have been initiated. This review describes the scientific data regarding safety and immunogenicity of the pandemic (H1N1) influenza vaccines which were approved for use in Israel. The approval was based on: (1) broad experience with seasonal flu vaccines; (2) data from the research and development processes of pandemic vaccines; (3) experience with adjuvants used in other vaccines and (4) post-marketing data. The immunogenicity of the approved vaccines is excellent: at least 92% develop protective antibody titers following a single vaccine dose. The vaccines are considered safe and severe side effects are very rare. Mild and transient adverse effects are similar to those following seasonal flu vaccines: local side effects in up to 12-18% and systemic adverse effects in up to 8%. The safety of the adjuvants and thiomersal is described in this review. The vaccines currently used in Israel were approved by the European Medicines Agency (EMEA) after the agency was satisfied with available safety data. Finally, the current pandemic 2009 (H1N1) influenza immunization program in Israel is described.

• Confluent molluscum contagiosum covering the eyelids of an HIV-positive child.

  Authors: Diana Averbuch, Tareq Jaouni, Jacob Pe'er, Dan Engelhard

  Clinical & experimental ophthalmology. 08/2009; 37(5):525-7.

• A partial form of recessive STAT1 deficiency in humans.

  Authors: Ariane Chapgier, Xiao-Fei Kong, Stéphanie Boisson-Dupuis, Emmanuelle Jouanguy, Diana Averbuch, Jacqueline Feinberg, Shen-Ying Zhang, Jacinta Bustamante, Guillaume Vogt, Julien Lejeune, Eleonore Mayola, Ludovic de Beaucoudrey, Laurent Abel, Dan Engelhard, Jean-Laurent Casanova

  The Journal of clinical investigation. 06/2009;

  Complete STAT1 deficiency is an autosomal recessive primary immunodeficiency caused by null mutations that abolish STAT1-dependent cellular responses to both IFN-alpha/beta and IFN-gamma. AffectedComplete STAT1 deficiency is an autosomal recessive primary immunodeficiency caused by null mutations that abolish STAT1-dependent cellular responses to both IFN-alpha/beta and IFN-gamma. Affected children suffer from lethal intracellular bacterial and viral diseases. Here we report a recessive form of partial STAT1 deficiency, characterized by impaired but not abolished IFN-alpha/beta and IFN-gamma signaling. Two affected siblings suffered from severe but curable intracellular bacterial and viral diseases. Both were homozygous for a missense STAT1 mutation: g.C2086T (P696S). This STAT1 allele impaired the splicing of STAT1 mRNA, probably by disrupting an exonic splice enhancer. The misspliced forms were not translated into a mature protein. The allele was hypofunctional, because residual full-length mRNA production resulted in low but detectable levels of normally functional STAT1 proteins. The P696S amino acid substitution was not detrimental. The patients' cells, therefore, displayed impaired but not abolished responses to both IFN-alpha and IFN-gamma. We also show that recessive STAT1 deficiencies impaired the IL-27 and IFN-lambda1 signaling pathways, possibly contributing to the predisposition to bacterial and viral infections, respectively. Partial recessive STAT1 deficiency is what we believe to be a novel primary immunodeficiency, resulting in impairment of the response to at least 4 cytokines (IFN-alpha/beta, IFN-gamma, IFN-lambda1, and IL-27). It should be considered in patients with unexplained, severe, but curable intracellular bacterial and viral infections.

• Mother to child transmission of human immunodeficiency virus: the Jerusalem experience, 1996-2006.

  Authors: Uriel Elchalal, Meytal Avgil, Tania Goslitzer, Diana Averbuch, Dan Engelhard, Michele Haouzi, Shlomo Maayan

  The Israel Medical Association journal : IMAJ. 11/2008; 10(10):667-71.

  BACKGROUND: In recent years, mother to child transmission of human immunodeficiency virus in the west has decreased markedly due to the advent of antiretroviral drugs given during pregnancy,BACKGROUND: In recent years, mother to child transmission of human immunodeficiency virus in the west has decreased markedly due to the advent of antiretroviral drugs given during pregnancy, cessation of lactation, and careful monitoring of viral load in the perinatal period. OBJECTIVE: To assess mother to child transmission of HIV among Ethiopian immigrants and non-Ethiopians in the Jerusalem area. METHODS: We conducted a prospective analysis of all deliveries of HIV-positive women in the Jerusalem district over a 10 year period. RESULTS: Between 1996 and 2006, 35 HIV+ women gave birth to 45 infants. Thirty-one (88%) of these women were of Ethiopian origin and gave birth to 39 infants. Of the 35 HIV+ women, 30 were aware of being HIV positive. They gave birth to 40 infants. Another 5 women (14%) were not aware of being HIV+ during delivery. They gave birth to five infants. Of the group of known HIV+ women, 26 (87%) were Ethiopian immigrants who delivered 34 infants and 4 were non-Ethiopians who delivered 6 infants. In the group of five women not aware of being HIV+, all were Ethiopians. Breast-feeding data were available for 32 of the 35 women. Only 2 women (6.2%) breast-fed their babies. Neither was aware of being HIV+. In the Ethiopian immigrant group (both known and unknown HIV status), 11 deliveries (28%) were vaginal, 18 (46%) were elective cesarean section and 10 (26%) were delivered by emergency cesarean section. Of the 26 known HIV+ Ethiopian women, 3 (12%) refused antiretroviral treatment despite repeated counseling. In the non-Ethiopian group, all deliveries were elective cesarean sections. Mother to child transmission of HIV occurred in 4 of the total 45 deliveries (8.8%). Of the 4 transmission cases, 2 occurred among 40 deliveries of known HIV+ women (5%), and 2 occurred among the 5 deliveries of women not aware of being HIV+ (40%, P=0.05). In the group of Ethiopian women only, HIV transmission occurred in 4 of 39 deliveries (10%), of which 2 occurred among 34 deliveries (5.8%) of women know to be HIV+ and 2 among 5 deliveries (40%) of women not aware of being HIV+ (P=0.08). CONCLUSIONS: Pregnant Ethiopian immigrants whose HIV status was known during pregnancy were at relatively high risk of HIV transmission despite the availability of antiretroviral drugs and counseling. This is likely due to inadequate adherence to ART preventive regimens, not dissimilar to the poor adherence observed among other immigrant groups in western countries. The substantial proportion of women, all Ethiopians, unaware being HIV+ at delivery, together with the significantly higher HIV transmission in that group compared to women who knew their HIV status, call for a revision of the current Ministry of Health opt-in policy for prenatal HIV screening.

• Empiric treatment with once-daily cefonicid and gentamicin for febrile non-neutropenic pediatric cancer patients with indwelling central venous catheters.

  Authors: Diana Averbuch, Rola Makhoul, Victoria Rotshild, Michael Weintraub, Dan Engelhard

  Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 08/2008; 30(7):527-32.

  SUMMARY: The approach to treating febrile non-neutropenic hematooncologic patients with central venous catheters varies. We recently introduced once-daily administration of cefonicid and gentamicinSUMMARY: The approach to treating febrile non-neutropenic hematooncologic patients with central venous catheters varies. We recently introduced once-daily administration of cefonicid and gentamicin for such children who were in good clinical condition and without focal signs of infection. Our 2-year experience of 125 episodes in 54 children is hereby reported. Absolute neutrophil counts were 550 to 16,700/mm. Bacteremia occurred in 6.4% episodes: only in patients with Hickman/Broviac catheters and not in those with port-a-caths [8/37 (21.6%) vs. 0/17 patients, P=0.046; 8/86 (9.3%) vs. 0/39 episodes, P=0.056]. The pathogens were coagulase-negative staphylococci (3), Streptococcus pneumoniae (2), Pseudomonas aeruginosa and Klebsiella pneumoniae (1), methicillin-sensitive Staphylococcus aureus (1), and Streptococcus milleri (1). All patients remained in stable clinical condition and all, except for 2 who became neutropenic and 1 with S. aureus bacteremia who developed cellulitis, defervesced while on the empiric therapy. Three episodes could not be managed as outpatients. No adverse effects were observed. We conclude that our approach is efficacious and safe and, furthermore, that empiric antibiotic therapy may not be indicated for selected patients with port-a-caths. Future study of children with Hickman/Broviac catheters will evaluate the use of cefonicid alone.

• [Hospitalizations associated with rotavirus gastroenteritis in Israel--a retrospective study]

  Authors: Galia Grisaru-Soen, Dan Engelhard, Sivan Pearl, Yechiel Schlesinger, Michal Shtein, Shai Ashkenazi

  Harefuah. 02/2008; 147(1):8-11, 96.

  BACKGROUND: Rotavirus is a major cause of infantile gastroenteritis worldwide and remains a common cause of hospitalizations in developed countries. The study aimed to assess the hospitalizations dueBACKGROUND: Rotavirus is a major cause of infantile gastroenteritis worldwide and remains a common cause of hospitalizations in developed countries. The study aimed to assess the hospitalizations due to rotavirus gastroenteritis in Israel and their characteristics. METHODS: A retrospective review of the records of children < 18 years hospitalized in six medical centers in Israel between April 2004 and March 2006 with acute gastroenteritis (AGE) and stool positive for rotavirus. Children with nosocomial infections, immune deficiency or under immunosuppressive therapy were excluded. RESULTS: During the study period, 1912 children were hospitalized with AGE due to rotavirus, of whom 1719 were included in this study. The peak rate of admission due to rotavirus was in November and December, when 34% of the admissions for AGE were caused by rotavirus, and the lowest rate was in August (7%, p < 0.0001). Annually, rotavirus caused 18.4% and 2.8% of the hospitalization for AGE and of all pediatric hospitalizations, respectively. The mean age on admission was 14 months (median 12 months) and the mean hospitalization--3.9 days. According to the annual pediatric statistics in Israel for 2004, the estimated annual rotavirus-associated hospitalization in Israel is 3816, with 14,692 hospitalization days. CONCLUSIONS: Rotavirus gastroenteritis is an important cause for hospitalizations and complications in children < 5 years in Israel, stressing the need for safe and efficacious vaccines to reduce the burden of the infection.