Prevalence of lipodystrophy in HIV-infected children: a cross-sectional study

Objective The aim of this study was to assess the changes in body fat distribution and lipid abnormalities in a population of HIV-infected children and adolescents followed in one single centre who had been exposed, or not, to antiretroviral therapy (ART).Materials and methods Patients aged between 3 and 19 years were evaluated in a cross-sectional study carried out between October and December 2002. Fat redistribution was evaluated independently by the physician and the patient. Fasting blood lipid profile, glucose, insulin and C peptide were measured. Among the 88 patients evaluated, 74 were taking ART.Results Fat redistribution was present in 20 patients, metabolic alterations alone were found in 22 children and 46 children had neither physical nor metabolic abnormalities. Patients with fat redistribution were found to have been on ART for a significantly longer period of time, with 42% of the children showing fat redistribution having been treated with anitretroviral agents for more than 5 years. These children had also been exposed to a higher number of antiretroviral agents. In contrast, metabolic alterations in the absence of fat redistribution were not related to the duration of ART nor to the number of drugs received. Treatment with stavudine or protease inhibitors was significantly associated with the presence of physical changes.Conclusion Regular assessment of fat redistribution and metabolic markers should be carried out in children treated with antiretroviral agents and taken into account when adapting therapy during the long-term follow up of these children.     

Neurocognitive function profile in HIV-infected school-age children

OBJECTIVES: Evaluation of neurocognitive function of school-age children with HIV. DESIGN: Cross-sectional observational study. METHODS: Twenty-two children (median age 9.46 years) with perinatally acquired HIV infection were administered a global intelligence test and tests from the Amsterdam Neuropsychological Tasks (ANT) program. The relationship between various patient-, disease- and treatment factors and neurocognitive outcome variables was examined. RESULTS: Compared with age-appropriate norms, mean IQ of the HIV-infected children was in the average range. However, the HIV-infected children performed poorer on several neuropsychological tests compared with age-appropriate norms. Executive function (attentional flexibility, visuospatial working memory) and processing speed emerged as the most sensitive cognitive measures in relation to HIV disease. The correlational analyses resulted in only two significant outcomes, showing that higher CD4% at initiation of highly active antiretroviral therapy (HAART) and longer treatment duration were associated with better working memory function and attentional control, respectively. CONCLUSIONS: These exploratory data suggest that subtle neurocognitive impairments may exist in HIV-infected school-age children, in particular characterized by compromised executive function and slowed information processing. Further research with larger sample sizes is needed to confirm these findings.     

Disclosure of HIV/AIDS diagnosis to HIV-infected children in Thailand

BACKGROUND: With the availability of highly active antiretroviral therapy, more HIV-infected children have lived longer. Many children are at the age that they should know the diagnosis. AIM: To identify the prevalence and patterns of disclosure of HIV/AIDS diagnosis to HIV-infected children. METHODS: A cross-sectional study was conducted among 103 main care givers of HIV-infected children aged > or =6 years who received highly active antiretroviral therapy at Chiang Mai University and Sanpatong district hospitals, northern Thailand. RESULTS: One-third (30.1%) of the children knew their HIV/AIDS status at an average age of 9.2 years. The care givers' understanding of 'knowing' did not always mean that the children were told the name of 'HIV' or 'AIDS'. Many of those care givers (84.3%) who reported that the child did not know their diagnosis had inaccurately explained to the child that he or she had some kind of disease such as allergy, lung, or liver disease. The most common reason for non-disclosure was the fear that disclosure might have negative psychological consequences to the child (53.4%). Almost all (88.7%) agreed that they should tell the children their diagnosis in the future but half needed health-care providers to help them at the event. CONCLUSION: There is a need for the development of disclosure guide-lines and models for health-care providers and care givers as there was a high rate of inaccurate disclosure and, in addition, care givers expressed their need for assistance from health-care providers for the future disclosure.     

Duration of hospitalization and appetite of HIV-infected South African children

Human immunodeficiency virus (HIV)-infected children generally show poor growth. Episodes of diarrhoea and pneumonia in HIV-infected children are thought to be more severe than in HIV-uninfected children. The objective of this study was to compare duration of hospitalization, appetite and nutritional status of HIV-infected children with that of uninfected children. A cross-sectional study was performed on children (2-24 months) admitted with diarrhoea or pneumonia to the university hospital. Children were tested for HIV, and the duration of hospitalization was noted for 189 children. Follow-up for blood analysis (n=154) and appetite measurement (n=48) was performed 4-8 weeks after discharge. Appetite was measured as ad libitum intake of a commercial infant cereal using highly standardized procedures. Hospitalization (in days) was significantly longer in HIV-infected children; among children admitted with diarrhoea (5.9 ± 1.9 vs. 3.8 ± 1.5) (mean ± standard deviation) and with pneumonia (9.0 ± 2.5 vs. 5.9 ± 1.9). Serum zinc, iron and transferrin concentrations, and haemoglobin levels were significantly lower in HIV-infected children compared with uninfected children. Appetites [amounts eaten (g) per kg body weight] of HIV-infected children were significantly poorer than those of HIV-uninfected children (18.6 ± 5.8 vs. 25.2 ± 7.4). The eating rates (g min(-1) ) of HIV-infected children were also slower (17.6 ± 6.2 vs. 10.1 ± 3.7) Mean Z-scores for length-for-age were significantly lower among HIV-infected children compared with HIV-uninfected children. Weight-for-length Z-scores were not significantly different. In summary, HIV-infected children had a 55% longer duration of hospitalization and a 21% lower appetite.     

Pain: a common symptom in human immunodeficiency virus-infected Thai children

Aim: To determine the prevalence and characteristics of pain in Thai human immunodeficiency virus-infected children. Methods: A cross-sectional study was performed at the HIV/AIDS outpatient clinic at the Queen Sirikit National Institute of Child Health, Bangkok, Thailand from November 2002 to January 2003. Sixty-one human immunodeficiency virus-infected patients aged 4 to 15 y, an equal number of age-matched children with no chronic disease and their caregivers participated. We interviewed children and their caregivers using a structured questionnaire on pain. The main outcome measure was the percentage of human immunodeficiency virus-infected children reporting pain. Results: Forty-four percent of the human immunodeficiency virus-infected children reported pain compared to 13% of the children with no chronic disease (odds ratio, OR = 5.3; 95% CI: 2.0-14.3). Seven percent of the infected children experienced chronic pain. Children in human immunodeficiency virus clinical categories B and C reported more pain than children in categories N and A (OR = 4.0, 95% CI: 1.1-14.7). Pain in infected children tended to occur in the abdomen, lower limbs or head. Only 44 percent of the infected children experiencing pain received analgesic medication.

Conclusion: Despite being a common experience, pain is insufficiently taken into account and treated in Thai children with HIV/AIDS. Therefore, adequate pain identification, assessment and management should be systemically considered in their routine care.     

The effect of nutritional support on weight gain of HIV-infected children with prolonged diarrhoea

AIM: To examine the effect on growth and immunity of enhanced calorie and protein provision to HIV-infected children presenting with prolonged diarrhoea. METHODS: A total of 169 HIV-infected children aged 6-36 months with diarrhoea for 7 days or more were randomly assigned to either standard nutrition support for children with prolonged diarrhoea or an enhanced diet started during hospitalisation and continued after discharge. The change in weight between enrolment and 8, 14 and 26 weeks and changes in plasma HIV-RNA and CD4 cell count at 8 and 26 weeks were estimated. RESULTS: Children receiving enhanced nutrition achieved significantly more weight gain (p < 0.001) between enrolment and 8 weeks than children on the standard diet (median increase in weight-for-age standard deviation score +1.02 vs. +0.01). After 8 weeks median weight velocity was normal and similar in both groups. The change in median CD4 count was similar in both groups. The 26-week mortality rate was high in both groups (standard support: 22%, enhanced support: 29%). CONCLUSIONS: Nutrition support of children with advanced HIV infection and prolonged diarrhoea resulted in significant and sustained weight gain, but did not improve CD4 counts or survival. These results support integrated nutrition interventions for HIV-infected children.     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Immune reconstitution inflammatory syndrome after initiating highly active antiretroviral therapy in HIV-infected children

The outcome of HIV infection has improved since the widespread availability of highly active antiretroviral therapy (HAART). Some patients, however, develop a clinical and radiological deterioration following initiation of HAART due to either the unmasking of occult subclinical infection or an enhanced inflammatory response to a treated infection. This phenomenon is believed to result from the restored ability to mount an immune response and is termed immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease. IRIS is widely reported in the literature in adult patients, most commonly associated with mycobacterial infections. There is, however, a paucity of data documenting the radiological findings of IRIS in children. Radiologists need to be aware of this entity. As a diagnosis of exclusion it is essential that the radiological findings be assessed in the context of the clinical presentation. This article reviews the common clinical and radiological manifestations of IRIS in HIV-infected children.     

Detection of HIV RNA by in situ hybridization in peripheral blood mononuclear cells of seronegative children born to HIV-infected mothers

Of 44 children born to human immunodeficiency virus (type 1) (HIV)-infected mothers, 11 have become seronegative. After the loss of maternal antibodies all children were analysed for several immunological functions and virological parameters in order to determine their HIV status. All children to date are clinically healthy and have normal immune functions. HIV-1 was detected by p24 antigen in one child, by in situ hybridization in nine children while viral cultures were all negative. These data suggest that the rate of vertical transmission of HIV-1 may be underestimated if seronegative children are considered to be not infected. They also suggest that molecular biological techniques are more sensitive than HIV antigen assay or viral cultures.     

Unexpected finding of laparoscopic appendectomy: appendix MALT lymphoma in children

Mucosa-associated lymphoid tissue (MALT) lymphomas comprise a group of indolent B-cell non-Hodgkin lymphomas (NHL), which are rare in pediatric age. The clinical presentation of MALT lymphomas varies according to the location of the lymphoma. We report on a case of MALT lymphoma involving the appendix in a 6-year-old girl. A 6-year-old girl was referred to our institution in May 2005 with a diagnosis of appendicitis. The abdominal ultrasound showed slight effusion in the pelvic fossa. The patient underwent laparoscopic appendectomy using the three-trocar technique. The appendix appeared moderately hyperaemic with slight enlargement of the two-thirds of the distal portion. The postoperative course was uneventful and the girl was discharged on day 1 without any complication. The morphological and immunohistochemical examination showed typical findings of low-grade MALT lymphoma (positivity for CD20, no immunostaing for CD5 and CD10, positivity for anti-λ light chain and low positivity for Ki-67). Further extensive examinations (abdominal MRI, gastroscopy, colonscopy and capsule endoscopy of the ileum) revealed that the lymphoma was limited to the distal two-third of the appendix (stage IA) and was not associated with any specific infection. At a recent follow-up the patients appeared to be doing well. Appendiceal MALToma is a rather uncommon pathology and, to our knowledge, there is only one report of appendiceal intussusception associated with appendiceal maltoma. According to our experience, low-grade MALToma can be managed by simple appendectomy. The histological examination should be the rule whenever an appendectomy is performed in children.     

Pathology of AIDS in children

AIDS in children is a multisystem disease. The various infections, degenerative, proliferative and vascular lesions can be classified into three categories based on the known, presumed or undetermined pathogenesis. The primary lesions are due to HIV infection. The associated lesions are related to direct or indirect sequelae of HIV infection or its treatment. The third category is of lesions of undetermined pathogenesis. The pediatric pathologist plays an important role in the study and management of AIDS by demonstrating new pathologic lesions, by making the etiologic diagnosis of infection in children with AIDS, and by providing clinicopathologic correlation which leads to better understanding of the disease process and its natural history. Diagnosis of neoplastic disorders is also made by the pathologist. There is a dearth of systematic pathologic study of AIDS in children in developing countries. Although no basic differences between pathologic lesions in pediatric AIDS in Western countries, and in developing countries is expected, such a study would lead to better understanding and better management of the disorder as it affects children from the developing countries.     

Management of vertically HIV-infected children in Europe

AIM: To describe policies for the therapeutic management of vertically HIV-infected children, and to compare these with practice, using children enrolled in a cohort study in the same setting. METHODS: A postal questionnaire survey of clinicians in the paediatric centres of the European Collaborative Study (ECS) was used. Prospective data collected within the ECS on the treatment and clinical status of infected children seen in these centres in 1999-2001 were analysed and compared with the year 2000 policies reported. RESULTS: In 3 of the 10 centres, the policy was routinely to administer antiretroviral therapy (ART) to infants upon confirmation of infection, and in 7 centres initiation of therapy was delayed until specific clinical, virological and immunological criteria were reached. Evidence of disease progression was a reason for treatment modification in all centres; other considerations included adherence problems and side effects. However, practice did not always match policy. For the 84 children with at least 5 y of follow-up (73 treated and 11 untreated), overall, 69% of the 420 person-years lived were spent without treatment, and 72% without any HIV-related symptoms. Untreated children were without symptoms for 94% of these 5 y, whereas treated children spent nearly a third of their time with mild or moderately severe symptoms. CONCLUSIONS: Therapeutic management of paediatric HIV disease requires a balance between preventing disease progression and minimizing adherence problems and side effects. This is important, as most infected children are without symptoms most of the time. Recent European consensus guidelines for the treatment of infected children will facilitate management.     

Hepatic Involvement in Dengue Fever in Children

Objective

Hepatic dysfunction is common in dengue infection and the degree of liver dysfunction in children varies from mild injury with elevation of transaminases to severe injury with jaundice. This study was undertaken to assess the spectrum of hepatic involvement in dengue infection.

Methods

110 children with serologically positive dengue fever aged between 2 months - 14 years were studied for their hepatic functions both clinically and biochemically after excluding malaria, enteric fever, Hepatitis A and Hepatitis B with relevant investigations.

Findings

All cases were grouped into DF (Dengue fever), DHF (Dengue hemorrhagic fever) and DSS (Dengue shock syndrome) according to WHO criteria. The spectrum of hepatic manifestations included hepatomegaly (79%), hepatic tenderness (56%), jaundice (4.5%), raised levels of aspartate transaminase (AST)(93%), alanine transaminase (ALT)(78%), alkaline phosphatase (AP) (57%), prolonged prothrombin time (PT) (20%), reduced levels of serum albumin (66%) and abnormal abdomen ultrasound (65%).

Conclusion

Hepatic dysfunction was observed more in DHF and DSS group compared to DF group. About 17.27% of children had >10 fold increase in the liver enzymes. There was no correlation between the degree of hepatic enlargement or hepatic tenderness with the abnormalities of liver functions. Any child with fever, jaundice and tender hepatomegaly in geographical areas where dengue is endemic, the diagnosis of dengue infection should be strongly considered.     

Primary liver tumours in children in Victoria: incidence and pathology

This paper reviews the incidence and pathology of liver tumours in children in the State of Victoria from 1955 to 1987. Seventy-four cases were found and are believed to represent all liver tumours in the State during that time. There were 29 benign and 45 malignant tumours. The benign tumours comprised 13 haemangiomas, 12 mesenchymal hamartomas, and 4 epithelial lesions. The malignant tumours were 30 hepatoblastomas, 8 embryonal sarcomas, 4 hepatocellular carcinomas, and 3 miscellaneous tumours. The haemangiomas were more commonly cavernous. Four were associated with skin lesions and 3 of these were capillary in type. Mesenchymal hamartomas varied from predominantly solid to predominantly cystic. All, however, contained hamartomatous collections of ducts and liver cells irregularly arranged in dense fibrous tissue. The commonest malignant tumour was hepatoblastoma, and there were 15 of predominantly epithelial type and 15 of mixed epithelial and mesenchymal type. The 8 undifferentiated sarcomas of embryonal pattern were characterised by pleomorphism of cells, bizarre giant cells, and extensive mucoid stromal change. Four examples of hepatocellular carcinoma were seen. All were multifocal and no further case has been seen for the last 15 years. The 3 miscellaneous tumours were gastrinoma, rhabdoid tumour, and myofibroblastic tumour of uncertain histogenesis. Incidence was calculated for the period of review. The rate for benign tumours was 0.81 per million children per year and for malignant tumours 1.33 per million children per year. Surgery for hepatobalstoma was shown to be the most important factor in improving survival.     

Liver transplantation in children

The results of liver transplantation has improved significantly in the last decade with one year survival figures close to 90% for children with chronic liver disease. This can be attributed to improvement in surgical techniques, better postoperative care and newer immunosuppresive drugs. As a result of this, increasing number of children are referred for transplantation with no significant increase in the number of solid organ donors. The earliest transplants in children were performed using organs from size matched pediatric donors. However, as the pediatric donor numbers were limited, liver reduction techniques were developed to transplant small children before deterioration. Increasing experience with reduced livers led to the development of split liver, living donor and auxiliary liver transplantation. Better management of immunosuppressive drugs and newer agents such as Mycophenolate Mofetil have reduced the incidence of graft loss due to chronic rejection and long-term renal toxicity. The goal for the future will remain to be transplantation without the use of longterm immunosuppression.     

Policy, ethics, and reproductive choice: Pregnancy and childbearing among HIV-infected women

As the numbers of women infected with HIV continue to increase, there are more calls for women who are HIV-infected not to have children, or for policies to be created that limit or try to influence the reproductive choices of HIV-infected women. Although motivated by legitimate concerns, such potential policies may be problematic in terms of their threats to the autonomy of women and considerations of justice. An alternative counseling approach is proposed that advocates encouraging HIV-infected women to make reasoned and considered decisions concerning childbearing. Such an approach would require providers to discuss with women not only the medical facts relevant to vertical transmission, but also many of the psychosocial issues relevant to the woman's interest in bearing a child. Moreover, the encounter would be contextualized to include discussion of issues unique to the woman's situation and other family considerations.     

Pulmonary infections in HIV-positive children

Infection of the lungs and airways by viral, bacterial, fungal and protozoal agents, often producing atypical radiographic features, is common in children with human immunodeficiency virus (HIV) infection. Conventional chest radiography and chest CT remain the most useful imaging modalities for evaluation of the immunocompromised patient presenting with a suspected pulmonary infection. In this review the radiological features of acute lung infections in this population are discussed.