Paediatric tuberculosis in Queensland, Australia: overrepresentation of cross-border and Indigenous children.

SETTING: Queensland, Australia. BACKGROUND: Understanding paediatric tuberculosis (TB) is important, as children with TB typically reflect recent community transmission. Children pose unique diagnostic challenges and are at risk of developing severe disseminated infection. OBJECTIVE: To describe the epidemiology, presentation and outcomes of children with TB disease in Queensland. DESIGN: This is a retrospective case series of children diagnosed with TB aged 0-16 years notified in 2005-2014. Data collected in the Queensland Notifiable Conditions System were extracted and analysed. RESULTS: Of 127 children diagnosed with TB, 16 were Australian-born (including 12 Indigenous Queenslanders), 41 were overseas-born permanent and temporary residents and 70 were cross-border Papua New Guinea (PNG) children; 88 children had pulmonary disease (with/without other sites) and 39 had extra-pulmonary disease only, with lymph node TB the predominant extra-pulmonary site; 70.1% of children had laboratory confirmation; and 14 cross-border children had multidrug-resistant TB. Treatment outcomes among children residing in Australia were good (100% among Australian-born and 97.2% among permanent and temporary residents), but they were less favourable among PNG children diagnosed in the Torres Strait Protected Zone (76.6%). CONCLUSION: Queensland has unique challenges in TB control, with a high proportion of cross-border diagnoses and over-representation of Indigenous children. Vigilance is needed given the wide spectrum of clinical presentation, particularly in high-risk communities.

Mitochondrial changes and oxidative stress in a mouse model of Zellweger syndrome neuropathogenesis.

Zellweger syndrome (ZS) is a peroxisome biogenesis disorder that involves significant neuropathology, the molecular basis of which is still poorly understood. Using a mouse model of ZS with brain-restricted deficiency of the peroxisome biogenesis protein PEX13, we demonstrated an expanded and morphologically modified brain mitochondrial population. Cultured fibroblasts from PEX13-deficient mouse embryo displayed similar changes, as well as increased levels of mitochondrial superoxide and membrane depolarization; this phenotype was rescued by antioxidant treatment. Significant oxidative damage to neurons in brain was indicated by products of lipid and DNA oxidation. Similar overall changes were observed for glial cells. In toto, these findings suggest that mitochondrial oxidative stress and aberrant mitochondrial dynamics are associated with the neuropathology arising from PEX13 deficiency.

Trends in the epidemiology of invasive Haemophilus influenzae disease in Queensland, Australia from 2000 to 2013: what is the impact of an increase in invasive non-typable H. influenzae (NTHi)?

Following the introduction of vaccination against Haemophilus influenzae type b (Hib), cases of invasive encapsulated Hib disease have decreased markedly. This study aimed to examine subsequent epidemiological trends in invasive H. influenzae disease in Queensland, Australia and in particular, assess the clinical impact and public health implications of invasive non-typable H. influenzae (NTHi) strains. A multicentre retrospective study was conducted from July 2000 to June 2013. Databases of major laboratories in Queensland including Queensland Forensic and Scientific Services (jurisdictional referral laboratory for isolate typing) were examined to identify cases. Demographic, infection site, Indigenous status, serotype, and mortality data were collected. In total, 737 invasive isolates were identified, of which 586 (79·5%) were serotyped. Hib, NTHi and encapsulated non-b strains, respectively, constituted 12·1%, 69·1% and 18·8% of isolates. The predominant encapsulated non-b strains were f (45·5%) and a (27·3%) serotypes. Of isolates causing meningitis, 48·9% were NTHi, 14·9% Hib, 14·9% Hie, 10·6% Hif, 6·4% Hia and 4·3% were untyped. During the study period, there was an increase in the incidence of invasive NTHi disease (P = 0·007) with seasonal peaks in winter and spring (P 0·001) and Hib (P = 0·039) than non-Indigenous patients. In Queensland, invasive H. influenzae disease is now predominantly encountered in adults and most commonly caused by NTHi strains with demonstrated pathogenicity extending to otherwise young or immunocompetent individuals. Routine public health notification of these strains is recommended and recent available immunization options should be considered.

Challenges to delivery of isoniazid preventive therapy in a cohort of children exposed to tuberculosis in Timor-Leste.

OBJECTIVES: To evaluate the number and geographic location of children aged <5 years exposed to sputum smear-positive tuberculosis (TB) in Timor-Leste, to determine the proportion evaluated for isoniazid preventive therapy (IPT) and to review the programmatic challenges present in delivering IPT to this cohort. METHODS: A total of 256 consecutive sputum smear-positive TB index cases diagnosed at Bairo Pite Clinic between August 2013 and July 2014 were interviewed about places of residence and household contacts <5 years of age in the 3 months preceding diagnosis. Attendance of these contacts for screening and the outcome of screening were recorded prospectively. RESULTS: The majority (225 of 256, 88%) of index cases resided in Dili, but 73 of 225 (32%) of these also had a second address outside the capital. A total of 255 contacts were identified; 172 of 255 (67%) of whom lived in Dili district and 83 of 255 (33%) of whom resided in remote districts. Only 66 of 255 (26%) contacts attended for evaluation for IPT, of whom 46 of 255 (18%) started IPT and nine of 255 (3.5%) were diagnosed with TB. Attendance was significantly less likely when the index case was not the parent of the child contact. CONCLUSIONS: Sputum smear-positive pulmonary TB cases frequently result in household exposure of children <5 years in Timor-Leste, and provision of IPT is suboptimal. Contacts are located in diverse and distant locations. Further studies to delineate access barriers to IPT and review programmatic models that will facilitate IPT scale up in Timor-Leste are needed.

The tangled web of non-canonical Wnt signalling in neural migration.

In all multicellular animals, successful embryogenesis is dependent on the ability of cells to detect the status of the local environment and respond appropriately. The nature of the extracellular environment is communicated to the intracellular compartment by ligand/receptor interactions at the cell surface. The Wnt canonical and non-canonical signalling pathways are found in the most primitive metazoans, and they play an essential role in the most fundamental developmental processes in all multicellular organisms. Vertebrates have expanded the number of Wnts and Frizzled receptors and have additionally evolved novel Wnt receptor families (Ryk, Ror). The multiplicity of potential interactions between Wnts, their receptors and downstream effectors has exponentially increased the complexity of the signal transduction network. Signalling through each of the Wnt pathways, as well as crosstalk between them, plays a critical role in the establishment of the complex architecture of the vertebrate central nervous system. In this review, we explore the signalling networks triggered by non-canonical Wnt/receptor interactions, focussing on the emerging roles of the non-conventional Wnt receptors Ryk and Ror. We describe the role of these pathways in neural tube formation and axon guidance where Wnt signalling controls tissue polarity, coordinated cell migration and axon guidance via remodelling of the cytoskeleton.

Invasive group A streptococcal disease in children in Queensland.

The epidemiology and clinical features of invasive group A streptococcal (iGAS) disease in Queensland children was investigated in response to anecdotal evidence of an increase in frequency and severity of this condition. A retrospective review of clinical records of all cases of iGAS disease notified to Queensland Health aged 0-18 years during a 5-year period was conducted. The annualized incidence of iGAS was 3·5/100,000 for the total population aged 0-18 and 13·2/100,000 for the Indigenous population of similar age. The annualized incidence was highest in Indigenous infants but no increase in frequency or severity of iGAS infections was observed. Findings included an increased prevalence in Indigenous children particularly in those aged <1 year, a significant male preponderance, lack of seasonal variation and an association with blunt trauma. Further studies are required to confirm and investigate these findings and to define specific risk factors in high-risk groups.

First outbreak of PVL-positive nonmultiresistant MRSA in a neonatal ICU in Australia: comparison of MALDI-TOF and SNP-plus-binary gene typing.

The purpose of this brief report is to describe the first outbreak of a community-associated nonmultiresistant and PVL-positive MRSA strain (CC30) in a neonatal intensive care unit in Australia. The utility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) for microbial typing is compared with single nucleotide polymorphism (SNP) plus binary gene analysis. The composite correlation index analysis of the MALDI-TOF-MS data demonstrated the similar inter-strain relatedness found with the SNP-plus-binary gene typing used to confirm the outbreak. The evolving spread of MRSA emphasizes the importance of surveillance, infection control vigilance and the ongoing investigation of rapid typing methods for MRSA.

Identification of MAL2, a novel member of the mal proteolipid family, though interactions with TPD52-like proteins in the yeast two-hybrid system.

The TPD52 (tumor protein D52)-like proteins are small coiled-coil motif-bearing proteins which were first identified though their expression in human breast carcinoma. TPD52-like proteins are known to interact in hetero-and homomeric fashions, but there are no known heterologous binding partners for these proteins. We now report the cloning of a novel member of the MAL proteolipid family, named MAL2, though its interaction with a TPD52L2 bait in a yeast two-hybrid screen. MAL2 is predicted to be 176 residues (19 kDa) with four transmembrane domains and is 35.8% identical to MAL, a proteolipid required in apical vesicle transport. The MAL2 prey bound all TPD52-like baits tested in the yeast two-hybrid system and in vitro translation of MAL2 produced a single 19-kDa (35)S-labeled protein which specifically bound full-length GST-Tpd52 in GST pull-down assays. The gene MAL2, which was localized to human chromosomal band 8q23 and shown to consist of four exons, is predominantly expressed in human kidney, lung, and liver. Our study has therefore identified a novel member of the MAL proteolipid family and potentially implicates TPD52-like proteins in vesicle transport.

Glycopeptide prescribing in an Australian tertiary paediatric hospital.

OBJECTIVE: To assess the extent and appropriateness of glycopeptide use in a tertiary Australian Paediatric hospital. METHODOLOGY: A retrospective analysis of prescriptions during a six-month period between July 1999 and January 2000. Medical records were examined and prescribing practices compared with the recommendations of the Hospital Infectious Control Practices Advisory Committee (HICPAC) and the Infectious Diseases Society of America (IDSA). RESULTS: Fifty-one patients were identified who received a total of 98 glycopeptide prescriptions. The Haematology/ Oncology unit prescribed 71/98 (72.4%). 68/98 (69.4%) patients received vancomycin, 9/98 (9.2%) received teicoplanin and 21/98 (21.4%) a combination of both. 81/98 (82.7%) had central venous catheters and 69/98 (70.4%) were immunocompromised. 48/98 (49%) prescriptions were for empiric treatment with 38/98 (38.8%) for prophylaxis and 11/98 (12.2%) therapeutic. 19/98 (19.4%) prescriptions were deemed appropriate, 6 (6.1%) by HICPAC criteria, and a further 13 (13.3%) by IDSA or other criteria. Of 19 prescriptions started appropriately, only 7/17 (41.1%) were continued appropriately beyond 48 h. Appropriate cultures were taken before prescription in 93.3% of cases. Dose was appropriate in 91/98 (92.9%) and frequency appropriate in all cases. The cost of inappropriate prescribing was approximately $9500. DISCUSSION: A high rate of inappropriate glycopeptide prescribing was evident in this paediatric population. Inappropriate prescribing existed across all subspecialties. Use was primarily for empiric therapy and prophylaxis in young children with an oncology diagnosis. A number of situations existed where glycopeptide prescription was felt appropriate despite not being included in HICPAC/IDSA guidelines. Areas with high rates of inappropriate prescribing were identified and will be targeted for education and intervention. Audit of practice continues.

VRE in the Republic of Ireland: clinical significance, characteristics and molecular similarity of isolates.

There have been increasing reports worldwide of vancomycin resistant enterococci (VRE) since they were first noted over ten years ago. This study sought to investigate the clinical significance of VRE in Ireland and to compare the phenotypic, genotypic and molecular characteristics of isolates recovered from patients in different institutions. The relative contribution of inter-hospital transmission of strains to the dissemination of VRE in Ireland was assessed. Hospital surveillance for VRE is not well established in Ireland. The organism has been detected in seven hospitals. Detection has been predominantly in oncology inpatients in large tertiary referral hospitals in the Dublin metropolitan area in whom strains generally represent asymptomatic gastrointestinal tract colonization. The predominant species is E. faecium with the Van A resistance phenotype. Twenty-seven (87) of 31 isolates from one unit were shown to be of the same or closely related strain as were 10 (63%) of 16 from another unit, indicating significant nosocomial transmission within institutions. There was no evidence for inter-hospital transmission of VRE. VRE is established in Ireland and nosocomial transmission readily occurs. Regular surveillance for VRE is indicated in high-risk populations in large institutions, specific risk factors for the acquisition of VRE need to be defined and optimal control and preventative strategies need to he instituted to detect and preempt the spread of this organism.

Eradication of vancomycin resistant Enterococcus faecium from a paediatric oncology unit and prevalence of colonization in hospitalized and community-based children.

We previously reported an outbreak of vancomycin resistant enterococci (VRE) in a paediatric oncology unit in December 1995 which was associated with widespread environmental contamination of the unit with VRE. We undertook this study to evaluate the effectiveness of the infection control policy instituted subsequent to the outbreak and to investigate the underlying prevalence of VRE colonization in hospitalized, outpatient and community-based children. We sought to establish the molecular similarity of VRE isolates from the study. Stool specimens were obtained from outpatients at risk of VRE, hospital inpatients and from healthy community-based children. VRE colonization was eradicated from the inpatient unit within 11 months, but in outpatients, 16 months after the outbreak, 4 of 137 (2.9 %) attending oncology outpatients, 5 of 65 (7.7%) with cystic fibrosis and 1 of 12 (8.3 %) with liver disease were found to be colonized with VRE. The isolates were all Enterococcus faecium, Van A phenotype except one E. casseliflavus of the Van C phenotype. All were unique in SmaI DNA macrorestriction patterns with the exception of two isolates, which were similar to the original outbreak strain and three further isolates of a single strain but which differed from the outbreak strain. Of 315 hospital inpatients, 2.5 % were colonized with VRE of the Van C resistance phenotype but VRE was not detected in 116 healthy, community-based children. We conclude that effective strategies can successfully control spread of VRE but despite a low prevalence of VRE colonization in hospital patients and in community-based children, outbreaks can occur when infection control practices are not optimal. Continued vigilance to detect VRE and limit spread within hospitals is therefore necessary.

Glycopeptide prescribing in a tertiary referral paediatric hospital and applicability of hospital infection control practices advisory committee (HICPAC) guidelines to children.

UNLABELLED: This study was undertaken to investigate the frequency of, indications for and appropriateness of glycopeptide prescription in a paediatric tertiary referral hospital and to assess the usefulness of the Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines. A prospective audit of all systemic glycopeptide prescriptions over a 2-month period was undertaken. Clinical and microbiological data were recorded. Of 2810 hospital admissions, systemic IV glycopeptides were prescribed on 57 occasions to 50 patients, 30 (52.6%) for vancomycin and 27 (47.4%) for teicoplanin. Prescriptions were for 34 males and 23 females aged from 2 weeks to 11 years (mean 15 months; median 9 months). Median hospital stay was 50 days. Glycopeptides were given to the following patient groups: cardiology 7 (12%), prophylaxis for cardiac surgery 11 (19%), post-cardiac surgery 1 (1.8%), oncology 14 (24.6%), post-gastrointestinal tract surgical 8 (14%), general surgical 9 (15. 8%) and medical 7 (12.3%). Twenty three children (41.8%) had central lines in situ. Reason for use of glycopeptide was therapeutic in 7 (12.3%), empiric in 38 (66.7%), and as prophylaxis in 12 (21.1%). Eight (14%) prescriptions met strict HICPAC criteria, but a further 22 (39%) prescriptions were considered appropriate in this high-risk population. Glycopeptides were chosen appropriately for cardiac surgery prophylaxis in a further 10 (18%) but timing and duration of use in this group was inappropriate. Of all prescriptions, use was empiric in 38 (76%) and appropriate cultures were obtained at the time of commencement in only 13 (34%) of these. Glycopeptides were not used for routine surgical prophylaxis or for first-line empiric treatment of febrile neutropenia. CONCLUSIONS: The strict implementation of HICPAC guidelines may not always be appropriate for children at risk of beta-lactam resistant gram-positive infections. Hospital guidelines need to be tailored to the patient population and microbial susceptibility patterns of each institution. Appropriate cultures should be obtained at the time glycopeptide treatment is begun so that duration of exposure can be limited.

Cloning of a third member of the D52 gene family indicates alternative coding sequence usage in D52-like transcripts.

D52 proteins are emerging as signalling molecules which may be regulators of cell proliferation. Having previously reported the existence of the human D52 gene family, comprising the hD52 and hD53 genes expressed in human breast carcinoma, we report the identification of a novel human gene hD54 (TPD52L2), which represents a third D52 gene family member. In situ mapping placed the hD54 gene on human chromosome 20q13.2-q13.3, a localization distinct from those of both hD52 and hD53 genes. The identified hD54 cDNAs predicted three hD54 isoforms, suggesting that alternatively-spliced transcripts may be produced from D52-like genes. This was confirmed by directly sequencing reverse transcriptase-polymerase chain reaction (RT-PCR) products amplified from D52-like gene transcripts expressed in developing and adult rat tissues, and by performing sequence analyses of the expressed sequence tag divisions of nucleotide databases. Alternative splicing of sequences encoding two regions, termed ins2 and ins3, was identified in one or more D52-like genes, with these alternative splicing events being differentially regulated. The functional consequences of alternative splicing were examined by characterizing the protein-protein interactions mediated by a truncated hD53 isoform within the yeast two-hybrid system. This hD53 isoform displayed altered interaction capabilities with respect to those of full-length hD53, suggesting that alternative splicing within the D52 gene family functions in part to alter the protein-protein interaction capabilities of encoded isoforms.

Paediatric HIV infection in the Republic of Ireland and the need for antenatal screening.

Thirty-seven HIV-infected children have been identified in the Republic of Ireland since 1985. Only 12 (32%) of 37 were followed prospectively from birth. Median age at diagnosis was 18 months (4 weeks to 8 years). In 32 (86%) of 37 cases, HIV infection was acquired as a result of transmission from mother to infant with intravenous drug use (IVDU) the most frequent risk factor for maternal acquisition of HIV. Of these 32 children, median maternal age at delivery was 24 (interquartile range (IQR) 23-26) years with median gestation at delivery 40 (IQR 38-40) weeks. Mode of delivery was by vaginal delivery in all 29 (91%) cases where mode of delivery is known. Only 2 infants were breastfed. Seven children have died at a median age of 9 (0.8-9.6) years. As of July 1997, 12 children have AIDS, 14 have symptomatic disease without AIDS and 3 are asymptomatic. Median age at AIDS diagnosis was 2.6 (0.1-6.5) years. Median survival time post-AIDS diagnosis was 6.5 (1.8-8.3) years. Of 29 living children, 24 mothers and 14 fathers are HIV infected and only 14 children live with both parents. Childhood HIV infection has had a significant personal, social and financial impact on both Irish families and society in general. More effective measures to control HIV infection among intravenous drug users are needed. Antenatal detection of HIV-infected mothers is paramount as vertical transmission can be successfully prevented and morbidity and death can be prevented in the infected infant.

Mother-to-child transmission of human immunodeficiency virus (HIV) in Ireland: a prospective study.

Symptomatic HIV infection was first diagnosed in an Irish child in 1985. A prospective study was initiated to determine the vertical transmission rate (VTR) of HIV and the average age of infant seroreversion and to monitor clinical, immunologic and virologic evidence for HIV infection in seroreverters. Ninety three HIV positive infants have been prospectively identified since 1985. The predominant underlying maternal risk factor for HIV infection is intravenous drug use (IVDU) (96 per cent). Of 93 infants, median gestational age was 40 weeks and median birth weight 3125 grams. Ninety-four per cent of infants were bottle fed. Currently 72 (77 per cent) infants are uninfected, 12 (13 per cent) are infected, 4 (4.5 per cent) are indeterminate and 5 (5.5 per cent) have been lost to follow up. The intermediate estimate of vertical transmission rate (VTR) is 14.3 per cent. The median age at documented seroreversion was 12 months. There are no significant differences between infected and non-infected children in male/female ratio, gestational age, mode of delivery or birth weight. Strategies to reduce the transmission of HIV among drug users in combination with routine antenatal screening and antiretroviral prophylaxis of vertical transmission are all measures which can reduce HIV infection in our children.

Perinatal transmission of HIV and diagnosis of HIV infection in infants: a review.

Paediatric HIV infection has become a major burden on families, communities and health services worldwide. The vast majority of children now acquire HIV as a result of mother to infant (vertical) transmission. Recent major advances have occurred following the greater understanding of the risk factors for perinatal transmission and the role of antiretroviral therapy in preventing transmission. Now that interruption of vertical transmission is possible, early identification of HIV-infected pregnant women is critical. As of June 1997, HIV infection has been diagnosed in 37 children under 15 yrs of age in the Republic of Ireland; 32 as a result of maternal to infant transmission. The exact timing of HIV transmission during pregnancy is unclear but it is estimated that 60-70 per cent of infants may be infected at the time of delivery with approximately 30 per cent infected earlier in gestation. Vertical transmission rates vary from 15-40 per cent in different global areas. Antenatal and perinatal zidovudine treatment can reduce this rate by 60-70 per cent. Risk factors for the vertical transmission of HIV-1 are multifactorial. These factors include maternal disease status, in particular maternal viral load, route of delivery, duration of membrane rupture, presence of obstetric complications and infant feeding practices. Definitive diagnosis of HIV infection in infancy has been difficult in the past. Direct viral detection methods now allow the reliable diagnosis of HIV infection in the first few months of life. The most effective intervention to reduce perinatal HIV infection will be the better identification of HIV positive pregnant women with the subsequent introduction of measures to interrupt vertical transmission of HIV.

Identification of homo- and heteromeric interactions between members of the breast carcinoma-associated D52 protein family using the yeast two-hybrid system.

The hD52 gene was originally identified through its elevated expression level in human breast carcinoma. Cloning of D52 homologues from other species has indicated that D52 may play roles in calcium-mediated signal transduction and cell proliferation. Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family. Since D52-like protein sequences are all predicted to contain a coiled-coil domain, we used the yeast two-hybrid system and glutathione S-transferase pull-down assays to investigate whether homo- and/or heteromeric interactions occur between D52-like proteins. Analyses of yeast strains co-transfected with paired D52-like constructs indicated that D52-like fusion proteins interact in homo- and heteromeric fashions through their predicted coiled-coil domains. Similarly, extensive two-hybrid screenings of a human breast carcinoma expression library identified hD53 and hD52 as potential interactors for both hD52 and hD53 baits. Thus, D52-like proteins appear to exert and/or regulate their activities through specific interactions with other D52-like proteins, which in turn may be intrinsic to potential roles of these molecules in controlling cell proliferation.

Control of a nosocomial outbreak of vancomycin resistant Enterococcus faecium in a paediatric oncology unit: risk factors for colonisation.

UNLABELLED: In order to determine the extent of vancomycin resistant enterococcus (VRE) colonisation within a paediatric oncology unit, the risk factors for the acquisition of the organism, the molecular epidemiology of the isolates and the impact of infection control measures, extensive patient and environmental surveillance was undertaken with identification, antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE) of all VRE isolates. A matched case control study was carried out. Fourteen patients (19% of screened patients) with VRE colonisation were identified (12 with Enterococcus faecium). All isolates manifested the Van A phenotype. Extensive environmental contamination with VRE was present. PFGE of E. faecium isolates from 10 patients and from five of six environmental cultures revealed patterns suggesting genetic relatedness. Following comparison of the 14 cases with 41 controls matched for age (+/- 4 years) and cohabitation on the oncology unit, risk factors for colonisation with VRE included duration of neutropenia, (OR, 3.72; 95% CI, 1.0-13.1), and antibiotic therapy, (OR, 4.07; 95% CI, 1.08-15.3), the number of antibiotic agents received, (OR, 8.4; 95% CI, 1.34-34.3) and the duration of therapy with amikacin, (OR, 10.7; 95% CI, 1.4-81.5), ceftazidime, (OR, 11.5; 95% CI, 2.2 59.9) or teicoplanin, (OR, 12.3; 95% CI, 2.25-67.4). Implementation of stringent infection control measures reduced environmental contamination from 25% of samples in week 1 to none in week 11. Two additional colonised patients were identified during the subsequent 6 months. CONCLUSION: Risk factors for VRE colonization in paediatric oncology patients included duration of neutropenia, duration of any antibiotic therapy, exposure to ceftazidime, amikacin or teicoplanin and the number of antibiotics used. The study suggests that environmental contamination played an important role in patient-to-patient transmission of VRE and interventions including implementation of infection control measures were associated with a decreased incidence of gastro-intestinal colonisation.

Risk of hepatitis C infection in neonates transfused with blood from donors infected with hepatitis C.

This look-back study was undertaken to identify newborn infants who had been infected with the hepatitis C virus (HCV) as a result of transfusions received before the introduction of routine screening in 1991 and to determine the transmission rates and persistence of transfusion-transmitted HCV infection acquired in the neonatal period. A total of 24 infants, transfused between 1980 and 1991, were identified as having received potentially infected blood from 11 blood donors. Ten of the donors had been administered batches of anti-D in 1977 known to have transmitted HCV genotype 1b infection. HCV RNA was detected in five of these donors when tested in 1994-95; the past donations of five of the donors, who had received anti-D immunoglobulin and had serological evidence of previous HCV infection but who were PCR negative when tested in 1994-95, were considered of lower risk. The source and time of acquisition of HCV infection for the one remaining donor in the study was not determined. Twenty-one (88%) of the 24 children were living at time of lookback. The median age at transfusion was 12 days. The median age at time of testing was 6.3 years. One child, who tested negative, was excluded from further analysis of HCV transmission, due to incomplete transfusion records. Overall, 12 of 20 (60%) children tested were positive for anti-HCV and seven (35%) were HCV RNA positive. Twelve (71%) of the 17 recipients of viraemic blood were ELISA positive and seven (41%) were PCR positive. Resolved HCV infection, as determined by ELISA pos, RIBA pos or indeterminate and PCR negativity, occurred in five of 12 (42%). In many instances there was more than one recipient per HCV infected donation. All of the reported children are clinically asymptomatic. However, the duration of HCV infection is relatively short and there is evidence of a degree of hepatitis in five of the seven children who are HCV RNA positive as judged by mildly elevated transaminase levels. The three who have undergone liver biopsy show mild hepatitis. The lower rates of persistence of HCV infection in this study may be due to the young age at exposure or to the source of infection which for all but one of the children was linked to one HCV genotype from female donors. Sharing of units of blood among multiple infants should be discouraged.