Effectiveness of highly active antiretroviral therapy administered by general practitioners in rural South Africa.

The purpose of this study was to assess the one-year efficacy of highly active antiretroviral therapy (HAART) administered by general practitioners in a primary care community clinic in rural South Africa. We performed an observational cohort study of 675 treatment-naive human immunodeficiency virus (HIV)-infected patients (including 66 children) who began HAART at least 12 months prior to the data analyses. Throughout treatment, the CD4+ T-cell count (percentage of CD4+ T-cells in children) and plasma HIV-RNA level were determined and the patient's weight was recorded. The primary outcome was mortality. Secondary outcomes were viral suppression, immunological response, and weight gain. One year after the start of HAART, 100 of the 675 (15%) patients were lost to follow-up and 119 patients (18%), including six children, died. Mortality was highest during the first few months of treatment. Based on an on-treatment analysis at one year after the start of therapy, 83% of adults and 71% of children had a viral load <400 copies/ml; the viral load was <50 copies/ml in 70% of adults and 61% of children. At one year, the mean CD4+ T-cell count in adults had increased by 236/mm(3), and the mean body mass index (BMI) had increased by 3.5 kg/m(2). In children, the mean CD4% had increased by 17.6. A low Karnofsky score and a low baseline CD4+ T-cell count were independently associated with death. In addition to these factors, a low baseline BMI and gender were predictive of a poor immunological outcome. Our study shows that adequately monitored HIV/acquired immunodeficiency syndrome (AIDS) care administered by general practitioners and their staff is feasible and leads to good results in a rural, primary care center in sub-Saharan Africa. In order to achieve even better results, early mortality should be reduced and efforts should be made to start HAART earlier.

[Episodes of angioedema in children with C1 esterase inhibitor deficiency]. / Aanvallen van angio-oedeem bij kinderen door C1-esteraseremmerdeficiëntie.

A 6-year-old boy and a 3.5-year-old girl presented with unexplained episodes of angioedema without urticaria. Low serum C1 esterase inhibitor activity was found in both children. Family history revealed autosomal dominant inheritance in the girl. The boy had a negative family history for angioedema. C1 esterase inhibitor deficiency is a rare but serious condition that may cause oedema of the upper respiratory tract and death by asphyxiation. Episodes of angioedema occur spontaneously, usually subsiding within 48-72 h. Between episodes, the patients are symptom free. Treatment consists of substitution of synthetic C1 esterase inhibitor during episodes of edema carrying a risk of upper airway obstruction. In patients who have more than one episode of severe angioedema per month, daily treatment with tranexamic acid should be considered. Both of these patients were not receiving daily treatment.

[Adjustment of the hepatitis-B vaccination scheme for newborns born to hepatitis-B virus carriers as of 1 January 2006]. / Aanpassing van het hepatitis B-vaccinatieschema voor zuigelingen van hepatitis B(HBsAg)-positieve moeders per 1 januari 2006.

Timely administration of hepatitis-B immunoglobulin postpartum combined with hepatitis-B vaccination will prevent the majority of vertical hepatitis-B virus transmissions. As of January 2006, the Dutch hepatitis-B vaccination scheme for newborns born to HBsAg positive mothers has been modified. Previously, the first vaccination was given at the age of 2 months. Newborns will now receive their first hepatitis-B vaccination preferably immediately following the administration of hepatitis-B immunoglobulin, within 2 hours after birth, or otherwise within 48 hours after birth. Booster vaccinations are scheduled at the ages of 2, 4 and 11 months, which are standard vaccination times in the Dutch national vaccination programme. The vaccination scheme for the other target-group of infants at increased risk of hepatitis-B virus infection has remained unchanged. As before, these infants will be vaccinated at 2, 4 and 11 months. It is also intended to measure the efficacy of vaccination by determining the anti-HBs antibodies 6 weeks after the last vaccination, at the age of 13 to 14 months. With this modification of the vaccination scheme, the Minister of Health follows the advice of the Health Council of the Netherlands. The goal is to increase the efficacy of hepatitis-B prevention in newborns born to HBsAg positive mothers.

Antibody neutralization of vascular endothelial growth factor (VEGF) fails to attenuate vascular permeability and brain edema in experimental pneumococcal meningitis.

To determine the contribution of vascular endothelial growth factor (VEGF) to cerebral edema formation in bacterial meningitis, we used a VEGF neutralizing antibody to block VEGF in rabbits, following induction of meningitis by intracisternal inoculation with 10(9) heat-killed pneumococci. At 8 h, cerebrospinal fluid (CSF) VEGF was significantly elevated in infected untreated animals, and correlated with CSF white blood cell (WBC) count (r=0.56, P=0.004), and brain water content (r=0.42, P=0.04). Blocking of VEGF did not attenuate brain edema, blood-brain barrier disruption, or CSF pleocytosis. The functional role of VEGF in the pathophysiology of BM remains elusive.

Reprogramming the host response in bacterial meningitis: how best to improve outcome?

Despite effective antibiotic therapy, bacterial meningitis is still associated with high morbidity and mortality in both children and adults. Animal studies have shown that the host inflammatory response induced by bacterial products in the subarachnoid space is associated with central nervous system injury. Thus, attenuation of inflammation early in the disease process might improve the outcome. The feasibility of such an approach is demonstrated by the reduction in neurologic sequelae achieved with adjuvant dexamethasone therapy. Increased understanding of the pathways of inflammation and neuronal damage has suggested rational new targets to modulate the host response in bacterial meningitis, but prediction of which agents would be optimal has been difficult. This review compares the future promise of benefit from the use of diverse adjuvant agents. It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several avenues to reprogram a wider array of mediators simultaneously are encouraging. Particularly promising are efforts to adjust combinations of cytokines, to inhibit neuronal apoptosis and to enhance brain repair.

[Three toddlers with a swelling in the neck]. / Drie peuters met een zwelling in de hals.

Three children, a girl aged 2.5 years and two boys aged 2 and 3 years respectively, presented with unilateral cervical lymphadenitis. The first patient had acute bacterial lymphadenitis due to group A Streptococcus, characterised by a painful cervical swelling of acute onset. The second patient had painless cervical lymphadenitis caused by Mycobacterium avium-intracellulare, which drained spontaneously. The third patient developed a non-tender, cervical swelling within a day. He too was systemically ill with fever and a headache. The lymphadenitis was caused by Bartonella henselae. After drainage, dissection and/or antibiotic therapy, all three recovered. A cervical mass in a young child is most frequently caused by an infectious lymphadenopathy. It rarely represents a malignant or other systemic disease. In many cases the diagnosis of infectious lymphadenitis can be made on the basis of the case history and clinical characteristics. However, when malignancy cannot be excluded tissue examination is always indicated.

[Serious invasive pneumococcal disease in young children: the importance of vaccination]. / Ernstige pneumokokkeninfecties bij jonge kinderen: het belang van vaccinatie.

In three children with fever, two girls aged 8 and almost 10 months and one boy aged 5 months, invasive pneumococcal disease was present. The youngest girl presented with pneumococcal sepsis which was complicated by haemolytic uraemic syndrome--she recovered--and the boy developed fulminant fatal pneumococcal sepsis/meningitis. The oldest girl was admitted for pneumococcal cellulitis and recovered. More than 80% of the cases of childhood invasive pneumococcal disease occur in children less than 2 years of age. However, the long available 23-valent pneumococcal polysaccharide vaccine is not effective in this age group. Recently, a 7-valent pneumococcal conjugate vaccine was registered in the Netherlands. This conjugate vaccine is effective in protecting infants and children from invasive pneumococcal disease. The Health Council of the Netherlands has recommended inclusion of the conjugate vaccine in the standard vaccine schedule. In the absence of a universal vaccination, the 7-valent pneumococcal conjugate vaccine is recommended for children at high risk of invasive disease.

[Pneumonia due to Legionella pneumophila in an immunocompromised child]. / Pneumonie bij een immuungecompromitteerd kind, veroorzaakt door Legionella pneumophila.

A one-year-and-seven-months-old boy was hospitalised because of fever, cough and general malaise. A diagnosed tonsillitis and pneumonia were treated with intravenous antibiotics. His clinical condition worsened despite antibiotic therapy. After immunologic investigations revealed both a cellular and a humoral immune disorder, a broncho-alveolar lavage was performed. The culture revealed Legionella pneumophila. Antibiotic treatment was then changed to erythromycin in combination with rifampicin, with a good response. Although rarely described in childhood, one should consider L. pneumophila as a possible pathogen in immunocompromised children presenting with pneumonia.

[HIV infection in children and the prevention of mother-to-child transmission]. / HIV-infectie bij kinderen en preventie van moeder-kindoverdracht.

The introduction of highly active antiretroviral therapy (HAART) has led to a major improvement in the prognosis of paediatric HIV in the developed world. HIV infected children in the Netherlands exhibit a broad range of social-cultural backgrounds and many of them grow up in multiple-problem families. As well as the impact of HIV itself, these families struggle with social, economic and emotional disadvantages that interfere with an optimal treatment. The failure of HAART and the development of HIV resistant strains resulting from non-compliance are increasingly being observed. For an optimal support of these children and families, an integrated medical and psychosocial service is required. HAART during pregnancy and delivery as well as post-exposure prophylaxis to the neonate have significantly decreased the risk of HIV transmission from mother to child. Due to the implementation of national guidelines and the effort of HIV-internists, obstetricians, midwives and paediatricians, less transmission cases have occurred in the Netherlands in recent years, despite an increasing number of exposed infants. The goal is to detect and treat every pregnant HIV-infected woman and her baby.