Progressive liver toxicity is a concern in HIV-infected patients. Although liver biopsy remains the gold standard for liver assessment, its invasiveness, sampling errors, variability in interpretation and expense do not make it an ideal routine follow-up exam. During the last decade, new non-invasive tools have been developed for the assessment of hepatic fibrosis in HCV and HIV/HCV co-infected patients.

OBJECTIVES:: Progressive liver injury is a concern in HIV-infected children exposed to long-term antiretroviral drugs and to the cytopathic effect of HIV. Yet liver biopsy is usually considered too invasive to be repeated in these patients. The aims of this study are to evaluate the feasibility of noninvasive hepatic investigations in HIV-1-infected children, assess the prevalence of signs of liver affection, and analyse the influence of the HIV disease severity and the exposure to antiretroviral therapy.MATERIALS AND METHODS:: A cross-sectional study conducted in 26 HIV-1 vertically infected children ages 8 to 18 years old. Liver function was assessed with standard serum biochemical markers, FibroTest, ActiTest, SteatoTest, Forns index, aspartate aminotransferase to platelet ratio index, ultrasound, and Fibroscan.RESULTS:: Nineteen (>60%) children had signs of liver affection on at least 1 of the test results: 13 (50%) had elevated liver enzymes, 15 (63%), 8 (33%), 5 (21%), and 5 (21%) had abnormal FibroTest, ActiTest, Forns index, and aspartate aminotransferase to platelet ratio index results, respectively. Four children (17%) had mild liver steatosis on ultrasound. Fibroscan measures were significantly higher in patients than in age-matched healthy children. Patients with elevated Fibroscan measures also had significantly higher FibroTest results. Age, HIV stage N in the Centers for Disease Control and Prevention classification and exposure duration to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor drugs were the main risk factors for hepatotoxicity.CONCLUSIONS:: More than half of our population of HIV-infected children had biological and/or radiological signs of liver affection. Regular follow-up of liver function is necessary in these patients, which is now possible with noninvasive procedures.

Natural selection is a major force behind the shaping of patterns of human genome variability. Inferences concerning the action of selection in the human genome provide a powerful tool for predicting regions of the genome of major functional importance. Genetic variants influencing human susceptibility to disease are likely to affect the fitness of the organism, unless the disease concerned begins late in the life. There is therefore an intimate relationship between disease and selection that can be exploited for the identification of candidate disease loci. To date, some of the strongest evidence for selection in the human genome has been obtained for genes involved in the immune response or host-pathogen interactions. Indeed, before the advent of antibiotics and vaccines, infectious diseases have been paramount among the threats to health and survival for most of human evolutionary history. I will review our most recent studies searching for the footprints of natural selection in the human genome. These studies, which go from global genomewide scans to more fine-tuned analyses in specific genes, highlight how the identification of selected loci or variants may provide insight into host genes or pathways playing an important role in pathogen resistance. For example, we have shown that natural selection has significantly driven the processes of population differentiation in modern human populations. Specifically, we have identified a number of genes under strong geographicallyrestricted positive selection, some of them involved in hostpathogen interactions. In addition, I will present our most recent data on the Toll-like receptor (TLR) signalling pathway. Our evolutionary data indicate that the different members of TLR family differ in their ecological relevance and increase our understanding of how variation in these genes results in different contributions to the outcome of infectious diseases. More generally, I will show how the identification of the extent and type of selection acting upon human genes involved in hostpathogen interactions make it possible to define the redundant and non-redundant functions of individual immunity-related genes in the natural setting. L2 Perspectives on pathogenesis and prevention of congenital herpes virus infection Mark R Schleiss Pediatric Infectious Diseases, University of Minnesota Medical School and Center for Infectious Diseases and Microbiology Translational Research, Minneapolis, MN, USA

Postural deformities are frequent in neonates. The moulded baby syndrome (MBS) comprises one or more of the following disorders: plagiocephaly, torticollis, congenital scoliosis, pelvic obliquity, adduction contracture of a hip and/or malpositions of the knees or feet. We analysed the incidence of MBS in healthy neonates and identified the risk factors of its composing elements. One thousand and one healthy neonates were examined on the second or third day of life by the same paediatrician. Familial, obstetrical, perinatal history and putative risk factors for postural deformities were collected. Families of newborns with a torticollis or plagiocephaly were given positioning advice and the outcome was evaluated by a phone survey 2 months later. MBS was detected in 107 neonates (10.7%): 97 plagiocephalies or torticollis, 25 congenital scoliosis or pelvic obliquities, and 13 malpositions of the knees or feet. We identified risk factors related to the mother (age: OR=1.39, parity: OR=0.643), to the obstetrical history (preterm labour: OR=1.65, oligoamnios: OR=10.179, breech presentation: OR=2.746, pregnancy toxaemia: OR=3.773, instrumental delivery: OR=6.028) and to the newborn (male gender: OR=1.982, birth length: OR=1.196). The initial plagiocephaly or torticollis improved in 77% of infants after 2 months of stimulation and positioning measures. Paediatricians should be alert regarding the frequent but subtle MBS postural deformities and give positioning advice to the parents. A neonate of male gender or greater birth length, with an older primiparous mother, a history of preterm labour, oligoamnios or pregnancy toxaemia, a breech presentation or an assisted delivery is more likely to have MBS.

Acta PaediatricaVolume 94, Issue 5 p. 636-637 A new PTPN11 mutation in juvenile myelomonocytic leukaemia associated with Noonan syndrome Lisa Giovannini, Lisa Giovannini Service de Pédiatrie, Hôpital de l’Archet, CHU Nice, FranceSearch for more papers by this authorHelene Cavé, Helene Cavé Laboratoire de Biochimie Génétique, Hôpital Robert Debré (AP-HP), 48 bd Serrurier 75019 Paris, FranceSearch for more papers by this authorCorinne Ferrero-Vacher, Corinne Ferrero-Vacher Laboratoire Central d’Hématologie, Hôpital de l’Archet, CHU Nice, FranceSearch for more papers by this authorPatrick Boutte, Patrick Boutte Service de Pédiatrie, Hôpital de l’Archet, CHU Nice, FranceSearch for more papers by this authorNicolas Sirvent, Corresponding Author Nicolas Sirvent Service de Pédiatrie, Hôpital de l’Archet, CHU Nice, France N. Sirvent, Service de Példiatrie, Hopital de l'Archet, CHU Nice, 151 route de Saint Antoine de Ginestiére, 06202 Nice Cedex 3, France. Tel: +33 4 92 03 60 64. Fax: +33 4 92 03 65 78. E-mail: sirvent.n@chu-niceSearch for more papers by this author Lisa Giovannini, Lisa Giovannini Service de Pédiatrie, Hôpital de l’Archet, CHU Nice, FranceSearch for more papers by this authorHelene Cavé, Helene Cavé Laboratoire de Biochimie Génétique, Hôpital Robert Debré (AP-HP), 48 bd Serrurier 75019 Paris, FranceSearch for more papers by this authorCorinne Ferrero-Vacher, Corinne Ferrero-Vacher Laboratoire Central d’Hématologie, Hôpital de l’Archet, CHU Nice, FranceSearch for more papers by this authorPatrick Boutte, Patrick Boutte Service de Pédiatrie, Hôpital de l’Archet, CHU Nice, FranceSearch for more papers by this authorNicolas Sirvent, Corresponding Author Nicolas Sirvent Service de Pédiatrie, Hôpital de l’Archet, CHU Nice, France N. Sirvent, Service de Példiatrie, Hopital de l'Archet, CHU Nice, 151 route de Saint Antoine de Ginestiére, 06202 Nice Cedex 3, France. Tel: +33 4 92 03 60 64. Fax: +33 4 92 03 65 78. E-mail: sirvent.n@chu-niceSearch for more papers by this author First published: 02 January 2007 https://doi.org/10.1111/j.1651-2227.2005.tb01955.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume94, Issue5May 2005Pages 636-637 RelatedInformation

To the Editor: Interleukin-2 (IL-2) is a cytokine secreted by activated T lymphocytes that regulates the proliferation and differentiation of lymphocytes, including CD4 T cells (1). HIV-infection is marked by functional and/or quantitative IL-2 deficiency (2). In adult HIV-1–infected patients with low CD4 cell count, sequential administration of IL-2 has been shown to improve immunologic function with no associated increase in plasma HIV RNA levels (3,4). We report a child infected with HIV through vertical transmission and treated with IL-2. The male patient was born on August 31 of 1986 to an HIV-1 seropositive mother. Diagnosis of infection was confirmed at the age of 18 months because of the persistence of HIV-1 antibodies. In April 1988 the patient received therapy with zidovudine (AZT), then didanosine (ddI), then stavudine (d4T) + ddI, and finally d4T + lamivudine (since February 1997). CD4 cell count slowly decreased (410 cells/mL in February 1997, 250 cells/mL in February 1999) in spite of persistent low viral load (PCR RNA <1000 copies/mL). Between November 1999 and October 2001, after informed consent was obtained, the patient received 8 doses of IL-2 (aldesleukine: Proleukin; Chiron, France), administrated subcutaneously twice a day during 3 consecutive days. The first four doses were administrated every 8 weeks, dose 5 to 8 every 10 weeks. Daily IL-2 doses progressively increased from 3 million IU/m2 to 9 million IU/m2. Safety, laboratory, virologic (viral load, PCR RNA–Roche monitor) and immunologic (lymphocyte subpopulations: CD3, 4, 8, 20, CD45RA, CD45RO) measures were assessed before each cycle of IL-2. The only clinically significant adverse effect was a flu-like syndrome (fever, headache, vomiting) at each dose (maximum grade III), which responded to symptomatic treatment. No abnormal values were noticed during biologic monitoring of the entire treatment. Change in CD4 cell count and viral load variation from baseline are reported in Figure 1. Memory (CD4-CD45RO) T cells slowly increased from baseline to the last assessment (week 108). The naive T cells (CD4/CD45RA) and CD4/CD8 ratio remained stable during treatment. Apart from a mild peak noticed on week 66 (550 copies/mL; 62% increased), viral load remained under the baseline value during treatment.FIG. 1.: Change in CD4 cell count and viral load (week 0: baseline assessment—first dose).We proposed IL-2 therapy to our patient because of the discrepancy between low viral load and slow but constant decrease in CD4 cell count. In HIV-infected adults, subcutaneous intermittent administration of IL-2 resulted in the best compromise between tolerance and efficacy (4). In our observation, the toxicity of IL-2 was not treatment-limiting. Adverse effects were mild to moderate, and similar to those reported in adult studies (3,4). The treatment was considered to be well tolerated, according to patient self-report. We noticed, as reported in studies of HIV-infected adults receiving active antiretroviral therapy, a substantial and sustained increase in CD4 cell count without increase in the plasma viral load. The long-term clinical benefits of the CD4 increase remain to be established. Fabrice Monpoux, M.D. Nicolas Sirvent, M.D. Jacqueline Cottalorda, M.D. Patrick Philip, M.D. Patrick Boutte, M.D.

Candiduria is rare in newborns and infants, occurring most often in patients with risk factors. When associated with a candidal bezoar in the urinary tract, candiduria is usually treated by systemic amphotericin B and flucytosine plus local irrigation with amphotericin B. We describe the successful treatment of five newborns with a urinary tract infection, on major urological malformations, due to Candida albicans (including three with a candidal bezoar) by fluconazole alone. No adverse effects or recurrences were observed. Fluconazole therapy permits early discharge from the hospital and seems suitable for infants and newborns with a C albicans urinary tract infection.