Diana Averbuch

Publications of Diana Averbuch

• Antibiotic treatment of children with community-acquired pneumonia: Comparison of penicillin or ampicillin versus cefuroxime.

  Authors: Yael Dinur-Schejter, Malena Cohen-Cymberknoh, Ariel Tenenbaum, Rebecca Brooks, Diana Averbuch, Sigmund Kharasch, Eitan Kerem

  Pediatric pulmonology. 03/2012;

  OBJECTIVE: Adherence to current guidelines for treatment of non-complicated community-acquired pneumonia (CAP) in children, recommending penicillin or ampicillin as first-line treatment, has beenOBJECTIVE: Adherence to current guidelines for treatment of non-complicated community-acquired pneumonia (CAP) in children, recommending penicillin or ampicillin as first-line treatment, has been poor. Our objective was to examine whether cefuroxime confers an advantage over penicillin or ampicillin for the treatment of children hospitalized with non-complicated CAP. PATIENTS AND METHODS: All children aged 3 months to 2 years with non-complicated CAP treated with penicillin or ampicillin or cefuroxime, admitted during 2003-2008, in the Departments of Pediatrics, Hadassah University Medical Center were included. Presenting signs, symptoms, laboratory findings at presentation, clinical parameters including number of days with IV antibiotics, oxygen treatment, length of hospital stay, change of antibiotics, and clinical course 72 hr and 1 week after admission, were compared. RESULTS: Of the 319 children admitted for non-complicated CAP, 66 were treated with IV penicillin or ampicillin, 253 with IV cefuroxime. Number of days of IV treatment, days of oxygen requirement, and days of hospitalization were similar (2.36 ± 1.6 days vs. 2.59 ± 1.6 days, 0.31 ± 1.2 days vs. 0.64 ± 1.3 days, and 2.67 ± 1.4 days vs. 2.96 ± 1.7 days, respectively). Treatment failure was not significantly different (7.6% vs. 4.7%). The number of patients who were febrile or required oxygen 72 hr after admission was similar (13.0% vs. 16.5% and 8.7% vs. 20.9%, respectively). One week after admission no difference between the two groups was seen. CONCLUSIONS: In previously healthy children, parenteral penicillin or ampicillin for treatment of non-complicated CAP in-hospital is as effective as cefuroxime, and should remain the recommended first-line therapy. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

• 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.

• 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.

• The use of blood counts and blood cultures to screen neonates born to partially treated group B Streptococcus-carrier mothers for early-onset sepsis: is it justified?

  Authors: Saar Hashavya, Shmuel Benenson, Zivanit Ergaz-Shaltiel, Benjamin Bar-Oz, Diana Averbuch, Smadar Eventov-Friedman

  The Pediatric infectious disease journal. 05/2011; 30(10):840-3.

  No clear recommendations exist regarding the approach to evaluate neonates born to partially treated group B Streptococcus (GBS)-carrier mothers for early-onset GBS (EO-GBS) sepsis. To determine theNo clear recommendations exist regarding the approach to evaluate neonates born to partially treated group B Streptococcus (GBS)-carrier mothers for early-onset GBS (EO-GBS) sepsis. To determine the yield and drawbacks of screening, all neonates born to GBS-carrier mothers who received only one dose of IV antibiotic, less than 4 hours, before delivery (partially treated). A retrospective analysis was performed of all complete blood counts (CBCs) and blood cultures obtained from infants born during the period 2005 to 2009 to GBS-positive screened mothers treated with only one dose of antibiotic prior to delivery. A review was conducted of all neonatal EO-GBS sepsis cases during the study period. : Of 5845 GBS-carrier mothers, 1648 (28%) received only one dose of antibiotic less than 4 hours before delivery. We traced the CBCs and blood cultures, which were taken from 1413/1648 (86%) infants after birth. In 234 (18%) of these 1413 neonates, a second CBC sample was taken due to abnormal result of the CBC (leukocytosis, leukopenia, or thrombocytopenia) or secondary to technical failure in obtaining the blood. None of the blood cultures taken in that screening protocol was GBS positive, but in 10 cases contamination with coagulase-negative Staphylococcus was reported. During the study period, EO-GBS sepsis was diagnosed in 11 neonates; all had clinical symptoms upon presentation. The use of CBC and blood culture to screen neonates born to GBS-carrier mothers who received only one dose of IV antibiotic before delivery led to a negligible clinical yield and a high rate of technical failure. Although these findings are in line with the recent change in the Centers for Disease Control guidelines, they put in question the cost of this practice in terms of neonatal pain and parental anxiety.

• 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.

• 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.

• Neonatal sepsis following maternal amnionitis by Edwardsiella tarda: a case report and a review of the literature.

  Authors: Saar Hashavya, Diana Averbuch, Itai Berger, Noa Ofek-Shlomai, Milena Pitashny, Carlos Hidalgo, Zivanit Ergaz

  European journal of pediatrics. 01/2011; 170(1):111-3.

  Edwardsiella tarda, a gram-negative bacterium, is a rare pathogen in the neonatal period. We present a term newborn that developed E. tarda septicemia following maternal amnionitis. The severeEdwardsiella tarda, a gram-negative bacterium, is a rare pathogen in the neonatal period. We present a term newborn that developed E. tarda septicemia following maternal amnionitis. The severe neurological outcome in this case, as well as in all other reported cases, highlights the need for meticulous neurological evaluation in neonates presenting with E. tarda septicemia even in the absence of bona fide meningitis.

• 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.

• Influenza A infection in young infants.

  Authors: David Rekhtman, Dana G Wolf, Floris Levy-Khademi, Diana Averbuch, Eitan Kerem, Isaiah D Wexler

  Archives of disease in childhood. 10/2010; 96(11):1085-7.

  To determine the clinical characteristics of infants ≤2 months old hospitalised with influenza A. The study was a retrospective analysis of infants ≤2 months old hospitalised with fever, respiratoryTo determine the clinical characteristics of infants ≤2 months old hospitalised with influenza A. The study was a retrospective analysis of infants ≤2 months old hospitalised with fever, respiratory distress and/or sepsis. Clinical signs, laboratory values, hospital duration and outcome were compared between children with influenza A and other viruses. The charts of 268 infants were reviewed. 29 (11%) children had laboratory-confirmed influenza A infection. Unique features associated with influenza infection included the high number presenting with fever (97%) and a history of exposure to family members with a flu-like illness (69%). A significantly lower rate of respiratory distress was observed in the influenza group compared with respiratory syncytial virus (RSV) (24% vs 89%, p≤0.001). Median duration of hospitalisation for influenza was shorter than RSV (4 days vs 6 days, p<0.001). In young infants, influenza A is a relatively mild disease compared to RSV and is primarily associated with upper respiratory tract manifestations.

• Rotavirus-associated colitis in a six-month-old baby.

  Authors: Saar Hashavya, Michael Wilscrhanski, Diana Averbuch, Dan Arbell, Orit Pappo, Eyal Shteyer

  Pediatrics international : official journal of the Japan Pediatric Society. 08/2010; 52(4):e204-6.

• 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.

• Steroids for deteriorating herpes simplex virus encephalitis.

  Authors: Banan Musallam, Israel Matoth, Dana G Wolf, Dan Engelhard, Diana Averbuch

  Pediatric neurology. 10/2007; 37(3):229-32.

  A 16-month-old girl presented with herpes simplex virus type 1 encephalitis with involvement of bilateral parietofrontal lobes, left thalamus and cerebellum. She was treated with intravenousA 16-month-old girl presented with herpes simplex virus type 1 encephalitis with involvement of bilateral parietofrontal lobes, left thalamus and cerebellum. She was treated with intravenous acyclovir. As her condition deteriorated, high-dose methylprednisolone was administered, resulting in remarkable improvement. This case suggests considering a short course of high-dose steroid therapy in severe herpes simplex encephalitis when there is clinical and radiologic deterioration in spite of appropriate antiviral therapy and decreasing viral load in the cerebrospinal fluid.

• Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy.

  Authors: Diana Averbuch, Jonathan M Schapiro, E Randall Lanier, Serge Gradstein, Giora Gottesman, Eynat Kedem, Menachem Einhorn, Galia Grisaru-Soen, Michal Ofir, Dan Engelhard, Zehava Grossman

  The Pediatric infectious disease journal. 11/2006; 25(11):1049-56.

  BACKGROUND: We retrospectively studied the effect of the lamivudine-induced reverse transcription mutation M184V on selection of thymidine analog mutations (TAMs) in HIV subtype C-infected childrenBACKGROUND: We retrospectively studied the effect of the lamivudine-induced reverse transcription mutation M184V on selection of thymidine analog mutations (TAMs) in HIV subtype C-infected children and on clinical outcome. METHODS: We genotyped 135 blood samples from 55 children. TAMs accumulation, viral load and clinical outcome were compared in children maintained on zidovudine/stavudine + lamivudine + protease inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NNRTI) despite loss of viral suppression and in children treated with, or switched to, other nucleoside reverse transcriptase inhibitors (NRTIs). Drug susceptibility and replication capacity of selected samples were measured. RESULTS: M184V developed in 18 of 22 of children who had received only zidovudine/stavudine + lamivudine + PI/NNRTI during a mean of 23.2 +/- 3.2 months versus in 3 of 14 children treated with other drugs and/or having multiple regimen changes (P = 0.001). TAMs appeared, respectively, in 2 of 22 versus 12 of 14 (P < 0.0001). The 2 groups did not differ significantly in baseline HIV-RNA or CD4 count, sampling time, and follow-up period. In M184V-containing samples, we found large reductions in susceptibility to lamivudine and emtricitabine but not to other NRTIs. When T215Y was present without M184V, susceptibility to zidovudine was reduced 8-fold. When both M184V + T215Y occurred, susceptibility to zidovudine was substantially increased. Average inhibition concentration 50 values were similar to those documented in the Stanford database for subtype B HIV with these mutation patterns. CONCLUSIONS: Maintaining a thymidine analog + lamivudine-based regimen reduced accumulation of TAMs and increased zidovudine susceptibility. This is likely the result of an increased susceptibility to thymidine analog (zidovudine) in the context of M184V documented here for the first time in subtype C-infected children. This retrospective study supports the strategy of maintaining lamivudine-containing therapy in subtype C-infected children. This strategy may be beneficially applied in the treatment of children in Africa, where thymidine analog + lamivudine-based regimen became available recently but further options are limited.

• Is Pneumocystis carinii pneumonia after stem cell transplantations a contagious disease?

  Authors: Igor B Resnick, Diana Averbuch, Memet Aker, Dan Engelhard

  Clinical transplantation. 07/2005; 19(3):427-31.

  We report of twins who underwent hematopoietic stem cell transplantation (HSCT) for neonatal acute leukemia. Hospitalized in the same room from the time the first one demonstrated respiratoryWe report of twins who underwent hematopoietic stem cell transplantation (HSCT) for neonatal acute leukemia. Hospitalized in the same room from the time the first one demonstrated respiratory symptoms, they both developed Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) 2 wk apart. This observation suggests that PCP may be a contagious disease in HSCT recipients. This may be especially true for infants and young children who are at risk of primary P. jiroveci infection, and should be avoided.

• Varicella zoster virus encephalitis in a previously healthy five-year-old child with herpes zoster ophthalmicus.

  Authors: Noa Ofek-Shlomai, Diana Averbuch, Dana G Wolf, Dan Engelhard

  The Pediatric infectious disease journal. 06/2005; 24(5):476-7.

• Mutation D30N is not preferentially selected by human immunodeficiency virus type 1 subtype C in the development of resistance to nelfinavir.

  Authors: Zehava Grossman, Ellen E Paxinos, Diana Averbuch, Shlomo Maayan, Neil T Parkin, Dan Engelhard, Margalit Lorber, Valery Istomin, Yael Shaked, Ella Mendelson, Daniela Ram, Chris J Petropoulos, Jonathan M Schapiro

  Antimicrobial agents and chemotherapy. 07/2004; 48(6):2159-65.

  Differences in baseline polymorphisms between subtypes may result in development of diverse mutational pathways during antiretroviral treatment. We compared drug resistance in patients with humanDifferences in baseline polymorphisms between subtypes may result in development of diverse mutational pathways during antiretroviral treatment. We compared drug resistance in patients with human immunodeficiency virus subtype C (referred to herein as "subtype-C-infected patients") versus subtype-B-infected patients following protease inhibitor (PI) therapy. Genotype, phenotype, and replication capacity (Phenosense; Virologic) were determined. We evaluated 159 subtype-C- and 65 subtype-B-infected patients failing first PI treatment. Following nelfinavir treatment, the unique nelfinavir mutation D30N was substantially less frequent in C (7%) than in B (23%; P = 0.03) while L90M was similar (P < 0.5). Significant differences were found in the rates of M36I (98 and 36%), L63P (35 and 59%), A71V (3 and 32%), V77I (0 and 36%), and I93L (91 and 32%) (0.0001 < P < 0.05) in C and B, respectively. Other mutations were L10I/V, K20R, M46I, V82A/I, I84V, N88D, and N88S. Subtype C samples with mutation D30N showed a 50% inhibitory concentration (IC(50)) change in susceptibility to nelfinavir only. Other mutations increased IC(50) correlates to all PIs. Following accumulation of mutations, replication capacity of the C virus was reduced from 43% +/- 22% to 22% +/- 15% (P = 0.04). We confirmed the selective nature of the D30N mutation in C, and the broader cross-resistance of other common protease inhibitor mutations. The rates at which these mutational pathways develop differ in C and subtype-B-infected patients failing therapy, possibly due to the differential impact of baseline polymorphisms. Because mutation D30N is not preferentially selected in nelfinavir-treated subtype-C-infected patients, as it is in those infected with subtype B, the consideration of using this drug initially to preserve future protease inhibitor options is less relevant for subtype-C-infected patients.