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Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102... more
Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infec...
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This study identified the ENT symptoms of 66 HIV infected children over an 8 year period (1986-1993) at Great Ormond Street Hospital for Children. The incidence, nature and age of onset of ENT symptoms were investigated; 91% of the... more
This study identified the ENT symptoms of 66 HIV infected children over an 8 year period (1986-1993) at Great Ormond Street Hospital for Children. The incidence, nature and age of onset of ENT symptoms were investigated; 91% of the children had ENT symptoms, the most common being cervical lymphadenopathy, oro-oesophageal candidiasis and otitis media. The HIV infected children suffered from the common ENT diseases of childhood. They also presented with specific conditions such as diffuse parotid swelling. Therefore, their clinical features differed from HIV infected adults as well as non-infected children. An increasing incidence of paediatric HIV infection was demonstrated by the study. Most were due to vertical transmission. ENT surgeons are likely to see more HIV infected children in future, either with the usual ENT diseases of childhood (to which they seem more susceptible) or with HIV-specific conditions. Although the diagnosis of HIV may be known, the ENT condition could be the initial presentation suggestive of immunodeficiency.
Research Interests: Humans, Child, Female, Male, Candidiasis, and 8 moreInfant, ENT, Hiv Infection, Clinical Sciences, Adult, Hiv seropositivity, Tonsillitis, and Lymph nodes
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The true prevalence of hepatitis C virus in children in the UK is not known and targeted screening is not standard practice despite an anticipated rise in new cases due to vertical transmission. An extension of the Department of... more
The true prevalence of hepatitis C virus in children in the UK is not known and targeted screening is not standard practice despite an anticipated rise in new cases due to vertical transmission. An extension of the Department of Health's 'look-back' exercise was undertaken in order to determine the prevalence of hepatitis C virus in high-risk patient groups who were transfused with blood and/or blood products before 1991. Five hundred and ninety-five patients transfused between 1971-91 were traced and offered counselling and testing. Blood samples from 405 were analysed for the presence of HCV antibodies and/or HCV RNA by RT-PCR and eight patients were found to be positive. The HCV seroprevalence rate in this cohort was 1.97% and the HCV genome detection rate was 1.72%. In view of the long-term complications from this infection and the availability of potentially effective anti-viral agents, we feel that targeted screening is of value in this setting.
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To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and... more
To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). United Kingdom and Ireland. 944 children with perinatally acquired HIV-1 under clinical care. Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > or = 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progre...
Research Interests: Mortality, Ireland, HIV, British medical history, United Kingdom, and 19 moreAntiretroviral Therapy, Humans, Child, Hospitalization, Female, Male, Infant, Follow-up studies, Hiv Infection, Risk factors, Newborn Infant, Great Britain, Public health systems and services research, Survival Rate, BMJ, Disease Progression, Risk Factors, Proportional Hazards Models, and Acquired immunodeficiency syndrome(Antiretroviral Therapy, Humans, Child, Hospitalization, Female, Male, Infant, Follow-up studies, Hiv Infection, Risk factors, Newborn Infant, Great Britain, Public health systems and services research, Survival Rate, BMJ, Disease Progression, Risk Factors, Proportional Hazards Models, and Acquired immunodeficiency syndrome)
(Antiretroviral Therapy, Humans, Child, Hospitalization, Female, Male, Infant, Follow-up studies, Hiv Infection, Risk factors, Newborn Infant, Great Britain, Public health systems and services research, Survival Rate, BMJ, Disease Progression, Risk Factors, Proportional Hazards Models, and Acquired immunodeficiency syndrome)
Human immunodeficiency virus (HIV) infection continues to be a vexing problem in the pediatric population. Otitis media, a common entity in immunocompetent as well as immunocompromised children, is prevalent in pediatric patients with HIV... more
Human immunodeficiency virus (HIV) infection continues to be a vexing problem in the pediatric population. Otitis media, a common entity in immunocompetent as well as immunocompromised children, is prevalent in pediatric patients with HIV infection. Recurrent infections and complications secondary to otitis media are also common in this population. The purpose of this review was to evaluate the records of a large group of children with HIV infection undergoing treatment for otitis media at a tertiary care center. Incidence of infections, severity of infections, and pathogens responsible were the key points of data collection in relation to each patient's HIV clinical and immunologic classification. We reviewed 72 patients with vertically-acquired HIV infection undergoing treatment at the Hospital for Sick Children, Great Ormond Street, London. All patients were born to HIV infected mothers of sub-Saharan African origin. A total of 32 (44.4%) of these children presented to our in...
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We have shown that the thrombocytosis which occurs in the 3rd and 4th week of Kawasaki disease is associated with the appearance in the circulation of platelet aggregating factors detected by the PAT test. These factors induce aggregation... more
We have shown that the thrombocytosis which occurs in the 3rd and 4th week of Kawasaki disease is associated with the appearance in the circulation of platelet aggregating factors detected by the PAT test. These factors induce aggregation and serotonin release from normal platelets. The aggregation can be blocked by EDTA and Prostacyclin. The aggregating factor appears to be of high molecular weight, and its activity was lost following fractionation at low pH. The platelet aggregating activity was significantly associated with the presence of IgG immune complexes, and these features suggest that IgG immune complexes are responsible for the platelet aggregating activity.
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ABSTRACT
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Human disease due to mycobacteria is a major cause of mortality and morbidity worldwide. In 1993, the World Health Organization (WHO) declared tuberculosis a global emergency after it became clear that there was a major resurgence of the... more
Human disease due to mycobacteria is a major cause of mortality and morbidity worldwide. In 1993, the World Health Organization (WHO) declared tuberculosis a global emergency after it became clear that there was a major resurgence of the disease. It is estimated that one - ...
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We report two infants with the acquired immunodeficiency syndrome (AIDS) and rectal bleeding due to cytomegalovirus (CMV) ileitis and colitis with minimal focal mucosal ulceration but with extensive leiomyolysis of the muscularis propria.... more
We report two infants with the acquired immunodeficiency syndrome (AIDS) and rectal bleeding due to cytomegalovirus (CMV) ileitis and colitis with minimal focal mucosal ulceration but with extensive leiomyolysis of the muscularis propria. Immunostaining and in situ hybridization for CMV showed numerous viral inclusions in the myocytes of the muscularis propria and vascular endothelium/smooth muscle with only occasional inclusions present in the muscularis mucosae. Colectomy was curative in one patient; in the other the bowel was only examined at postmortem.
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ABSTRACT Pulmonary infections are the commonest type of illnesses seen in everyday practice. Although most infections are caused by a few familiar pathogens, an increase in global travel has led to the occurrence of rare and exotic... more
ABSTRACT Pulmonary infections are the commonest type of illnesses seen in everyday practice. Although most infections are caused by a few familiar pathogens, an increase in global travel has led to the occurrence of rare and exotic diseases that often do not manifest until after the traveller returns home. Previously innocuous organisms may also be the cause of exotic infections in patients undergoing transplantation, or very aggressive immunosupression. Such treatment regimes may reactivate quiescent organisms acquired years previously, for example melioidosis and strongyloides stercoralis. In most developed countries there is also an increasing incidence of zoonotic infections, with a number of these presenting with mainly pulmonary symptoms. A carefully taken history of recent travel, exposure to wild or domestic animals or the presence of immunosuppression, is extremely helpful in identifying problematic infections that fall into the realm of the exotic. This review discusses some of the respiratory infections in each of these groups with an emphasis on imported infections.
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The most common presentation of mycobacterial infection encountered in otolaryngological practice is cervical lymphadenitis. We report a child with an unusual cause of cervical lymphadenopathy, i.e. dual tuberculous infections. This had... more
The most common presentation of mycobacterial infection encountered in otolaryngological practice is cervical lymphadenitis. We report a child with an unusual cause of cervical lymphadenopathy, i.e. dual tuberculous infections. This had clinical ramifications as, initially Mycobacterium avium-intracellulare was grown in culture and was resistant to standard anti-tuberculous agents, and hence treated with excision of the lymph node. However, the cultures from the excised lymph node grew out Mycobacterium tuberculosis that was sensitive to standard anti-tuberculous drugs. To our knowledge, no such presentation has been reported previously. We also review the literature on cervical lymphadenitis due to atypical mycobacteria and Mycobacterium tuberculosis, with particular emphasis on clinical presentation, diagnosis and management.
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This study identified the ENT symptoms of 66 HIV infected children over an 8 year period (1986-1993) at Great Ormond Street Hospital for Children. The incidence, nature and age of onset of ENT symptoms were investigated; 91% of the... more
This study identified the ENT symptoms of 66 HIV infected children over an 8 year period (1986-1993) at Great Ormond Street Hospital for Children. The incidence, nature and age of onset of ENT symptoms were investigated; 91% of the children had ENT symptoms, the most common being cervical lymphadenopathy, oro-oesophageal candidiasis and otitis media. The HIV infected children suffered from the common ENT diseases of childhood. They also presented with specific conditions such as diffuse parotid swelling. Therefore, their clinical features differed from HIV infected adults as well as non-infected children. An increasing incidence of paediatric HIV infection was demonstrated by the study. Most were due to vertical transmission. ENT surgeons are likely to see more HIV infected children in future, either with the usual ENT diseases of childhood (to which they seem more susceptible) or with HIV-specific conditions. Although the diagnosis of HIV may be known, the ENT condition could be the initial presentation suggestive of immunodeficiency.
Research Interests: Humans, Child, Female, Male, Candidiasis, and 8 moreInfant, ENT, Hiv Infection, Clinical Sciences, Adult, Hiv seropositivity, Tonsillitis, and Lymph nodes
Kawasaki disease (KD) is a systemic vasculitis of childhood with widespread vascular endothelial damage in the acute stage. Long-term complications, such as myocardial infarction and death, are recognized, but the extent and nature of... more
Kawasaki disease (KD) is a systemic vasculitis of childhood with widespread vascular endothelial damage in the acute stage. Long-term complications, such as myocardial infarction and death, are recognized, but the extent and nature of late vascular abnormalities that might predispose to these events have not been studied. We used high-resolution ultrasound to study endothelial function in the brachial artery of 20 patients 5 to 17 years after acute KD (median, 11 years) and compared findings with those in 20 age- and sex-matched control subjects. Vascular responses to reactive hyperemia (with flow increase leading to endothelium-dependent dilation) and to sublingual glyceryl trinitrate (GTN; endothelium-independent dilation) were recorded. The relationship between endothelium-dependent vascular responses and features of the endothelium acute illness was examined. There was no difference in baseline vessel diameter, degree of reactive hyperemia, or response to GTN between patients and control subjects. In contrast, flow-mediated dilation was markedly reduced in KD patients compared with control subjects (3.1% versus 9.4%; P &amp;amp;lt; .001). Late endothelium-dependent responses were not related to features of the acute illness. Abnormalities of systemic endothelial function are present many years after resolution of acute KD, even in patients without detectable early coronary artery involvement. Because this may be an important factor in the genesis of late vascular complications, long-term follow-up of all patients with KD is indicated.
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To determine the provision of services for children with tuberculosis (TB) living in the UK. A postal questionnaire was sent to the most appropriate paediatrician and adult physician in every acute hospital trust in the UK. Information... more
To determine the provision of services for children with tuberculosis (TB) living in the UK. A postal questionnaire was sent to the most appropriate paediatrician and adult physician in every acute hospital trust in the UK. Information was sought on inpatient and outpatient services for children with TB and for children in contact with TB. Responses were received from 323 individuals in 199 of the 205 trusts approached. The median number of children with TB seen per year at each trust was 1.5 (range 0-30). Inpatients were nearly all admitted to paediatric wards (197 (99%) trusts). In 141 trusts (71%) they were looked after solely by paediatricians or jointly by paediatricians and physicians (47 trusts, 24%). 132 (66%) trusts stated there was a named consultant for children with TB. Negative pressure isolation rooms were reported to be available for children in 42 trusts (21%). As outpatients, children with TB were seen in paediatric clinics in 163 (82%) trusts. Only 10 (5%) trusts had designated family TB clinics. Children in contact with TB were managed by paediatricians in 81 (38%) trusts, by physicians in 67 (34%) trusts and jointly in 51 (26%) trusts. 161 (81%) trusts had access to a TB nurse and directly observed therapy (DOTS) was available in 116 (58%) trusts. Many paediatricians see few children with TB, but most children with TB are looked after by general paediatricians alone. The survey supports national recommendations to develop family clinics and clinical service networks for children with TB, which may improve the care of these children.
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A year after the Department of Health issued guidelines on post exposure prophylaxis (PEP) for health care workers exposed to HIV, we conducted a telephone survey of occupational health nurses and junior doctors in London teaching... more
A year after the Department of Health issued guidelines on post exposure prophylaxis (PEP) for health care workers exposed to HIV, we conducted a telephone survey of occupational health nurses and junior doctors in London teaching hospitals, to assess implementation of the guidelines and awareness among junior doctors of local policies. The management and administration of PEP for HIV differed considerably between hospitals. Many junior doctors did not know what to do in the event of a needlestick injury. Both the implementation of and the briefing of staff about current management policies need to improve.
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Mannose-binding lectin (MBL; encoded by MBL-2) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation and cell lysis. Mutations in the MBL-2 promoter and of the MBL-2... more
Mannose-binding lectin (MBL; encoded by MBL-2) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation and cell lysis. Mutations in the MBL-2 promoter and of the MBL-2 gene exon 1 result in reduced protein levels and increased susceptibility to infection. We have investigated the effect of MBL-2 polymorphisms on susceptibility and progression of HIV-1 infection in children. One-hundred and twenty-eight children, aged 2-16 years were recruited. MBL-2 genotypes were determined by PCR and heteroduplex analyses. Serum MBL levels were measured by ELISA. Comparison of genotypes (A=wild type, O=variant alleles) and protein levels between groups was performed using chi-squared, Mann-Whitney U or Kruskal-Wallis tests. Children were classified according to the Centers for Disease Control and Prevention clinical classification: A, B or C (mildly symptomatic [n=39], moderately symptomatic [n=58] or severely symptomatic AIDS [...
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There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children. Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or... more
There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children. Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q12h) were included in this single-arm, open-label, crossover study. Intensive plasma PK sampling was performed at steady state, after which children switched to q24h dosing and PK sampling was repeated 4 weeks later. Daily area under the curve (AUC0-24) and peak level (Cmax) of q24h and q12h regimens were compared by geometric mean ratios (GMRs) with 90% confidence intervals (CIs). Children were followed for 24 weeks to evaluate safety and virological response. 24 children were enrolled, of whom 20 [median age (range) 5.6 (2.1-12.8) years] had evaluable PK data for 3TC (n=19) and/or ABC (n=14). GMRs of 3TC and ABC AUC0-24 and Cmax q24h versus q12h significantly exceeded 1.0. GMRs were not significantly differe...
Research Interests: Microbiology, Medical Microbiology, Adolescent, HIV, Humans, and 20 moreChild, Female, Male, Infant, Follow-up studies, Netherlands, Hiv Infection, Steady state, Clinical Sciences, Great Britain, Adverse Event, Highly Active Antiretroviral Therapy, Age Factors, Combination drug therapy, Antiviral Activity, Lamivudine, Area Under the Curve, Cross-Over Studies, Confidence Interval, and Viral Load(Child, Female, Male, Infant, Follow-up studies, Netherlands, Hiv Infection, Steady state, Clinical Sciences, Great Britain, Adverse Event, Highly Active Antiretroviral Therapy, Age Factors, Combination drug therapy, Antiviral Activity, Lamivudine, Area Under the Curve, Cross-Over Studies, Confidence Interval, and Viral Load)
(Child, Female, Male, Infant, Follow-up studies, Netherlands, Hiv Infection, Steady state, Clinical Sciences, Great Britain, Adverse Event, Highly Active Antiretroviral Therapy, Age Factors, Combination drug therapy, Antiviral Activity, Lamivudine, Area Under the Curve, Cross-Over Studies, Confidence Interval, and Viral Load)
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To establish the levels of dental caries and gingivitis in a group of HIV-positive children. The study group comprised 35 children with the Human Immunodeficiency Virus attending The Great Ormond Street Hospital For Children. Outcome... more
To establish the levels of dental caries and gingivitis in a group of HIV-positive children. The study group comprised 35 children with the Human Immunodeficiency Virus attending The Great Ormond Street Hospital For Children. Outcome measures included the number of decayed, missing and filled teeth and surfaces in both the primary and permanent dentitions; plaque and gingivitis scores. The children included 18 boys and 17 girls. They were aged from 6 months to 18 years, with 17 aged 5 years or less and 15 aged 6 years or older. Twenty-four of the 35 children had some caries experience. The mean DMFT was 4.4 and for those with permanent teeth the mean DMFT was 0.7. Mean plaque and gingivitis scores were 16.7 and 5.1 for plaque and gingivitis adjacent to primary teeth and 8.0 and 5.7 for that related to permanent teeth. There is a significant treatment need for children with HIV.
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Bacille Calmette-Guerin (BCG) is one of the most widely used vaccines throughout the world. Children of temporary residents in the United States frequently undergo tuberculin skin testing as part of their health maintenance visits.... more
Bacille Calmette-Guerin (BCG) is one of the most widely used vaccines throughout the world. Children of temporary residents in the United States frequently undergo tuberculin skin testing as part of their health maintenance visits. Management of those children with a positive skin test can lead to doctor-parent disagreements, because of differences in tuberculosis (TB) policies between the United States and other countries that routinely administer BCG vaccine. Two British specialists compare their approach with that of the United States. They also discuss the potential for specific diagnosis of latent TB infection with interferon-based TB diagnostic blood testing, to distinguish positive skin tests caused solely by BCG vaccination.
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Varicella is usually a benign and self-limited disease of infancy and childhood although it has been recognized that it sometimes has severe and life-threatening complications. We report a case of postinfectious purpura fulminans with... more
Varicella is usually a benign and self-limited disease of infancy and childhood although it has been recognized that it sometimes has severe and life-threatening complications. We report a case of postinfectious purpura fulminans with acquired protein S deficiency following varicella in a 6-year-old child and discuss the underlying mechanism of postinfectious purpura fulminans.
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There are few data about disease progression and response to antiretroviral therapy (ART) in vertically HIV-infected infants in the era of effective therapy. Cohort study. We examined progression to acquired immunodeficiency syndrome... more
There are few data about disease progression and response to antiretroviral therapy (ART) in vertically HIV-infected infants in the era of effective therapy. Cohort study. We examined progression to acquired immunodeficiency syndrome (AIDS) and death over calendar time for infants reported to the National Study of HIV in Pregnancy and Childhood in the United Kingdom/Ireland. The use of ART and CD4 and HIV-1 RNA responses were assessed in a subset in the Collaborative HIV Pediatric Study. Among 481 infants, mortality was lower in those born after 1997 (HR 0.30; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), with no significant change in progression to AIDS. Of 174 infants born since 1997 in the Collaborative HIV Pediatric Study, 41 (24%) were followed from birth, 77 (44%) presented pre-AIDS and 56 (32%) presented with AIDS. Of 125 (72%) children on 3- or 4-drug ART by the age of 2 years, 59% had HIV-1 RNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;400 at 12 months; median CD4 percentage increased from 24% to 35%. Among 41 infants followed from birth, 12 progressed to AIDS (5 while ART naive) and 3 died; 1 of 10 infants initiating ART before 3 months of age progressed clinically. Mortality in HIV-infected infants is significantly lower in the era of effective ART, but symptomatic disease rates remain high. Infrequent clinic attendance and poor compliance with cotrimoxazole prophylaxis and/or ART in infants born to diagnosed HIV-infected women and late presentation of infants identified after birth appear to be major contributors. Poor virologic response to ART during infancy is of concern because of increased likelihood of early development of resistance.