Niels Henrik Valerius

Mother to child transmission of HIV infection in the era of highly active antiretroviral therapy

BACKGROUND Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. METHODS Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. RESULTS Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001-2003. The overall MTCT rate in this period was 2.87% (95% confidence interval [CI], 2.11%-3.81%), but it was 0.99% (95% CI, 0.32%-2.30%) during 2001-2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1; P=.003) and elective Caesarean section (AOR, 0.33; P=.04). Detection of maternal HIV RNA was significantly associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03-0.33), compared with vaginal delivery or emergency Caesarean section. CONCLUSIONS Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important.

Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea.

Background. Oral bacteriotherapy promotes recovery from acute childhood diarrhea, but few strains have been shown to have therapeutic potentials. We examined the effect of two newly identified probiotic Lactobacillus strains in acute childhood diarrhea. Methods. Sixty-nine children were randomized during hospitalization for acute diarrhea to receive a mixture of Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 1010 colony-forming units of each strain or placebo twice daily for 5 days. Before selection of these stains their potential probiotic characteristics were demonstrated in vitro and in healthy volunteers. Results. In patients receiving probiotics, the diarrheal phase was reduced by 20%. The duration of diarrhea was 82 h in the treatment group vs. 101 h in the control group (not significant, P = 0.07). However, 3 of 30 patients from the treatment group vs. 13 of 39 from the control group still had loose stools at the end of the study period (P = 0.03). In patients with diarrhea for <60 h before start of treatment (early intervention), a clear effect of the probiotics was demonstrated (80 h in the treatment group vs. 130 h in the control group, P = 0.003). After early intervention, the length of hospitalization was reduced by 48% (3.5 vs. 1.7 days, P = 0.03). At the end of the intervention, rotavirus antigen was found in 12% of patients from the treatment group vs. 46% from the control group (P = 0.02). Conclusions. The two probiotics, L. rhamnosus 19070-2 and L. reuteri DSM 12246, ameliorated acute diarrhea in hospitalized children and reduced the period of rotavirus excretion. Oral bacteriotherapy was associated with a reduced length of hospital stay. The beneficial effects were most prominent in children treated early in the diarrheal phase.

Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers

Background. Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children. Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea. Methods. We studied in a randomized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 1010 colony-forming units of each strain twice daily for 5 days, on acute diarrhea in children in a cohort of children recruited from local day-care centers. The duration of diarrhea and assessment of stool consistency were recorded by the parents. Results. In patients treated with the selected Lactobacillus strains, the mean duration of diarrhea after intervention was reduced (76 h in patients treated with probiotics vs. 116 h in the placebo group;P = 0.05). In patients with diarrhea for <60 h before start of treatment (early intervention), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h in the placebo group (P = 0.02); 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment (P = 0.03). Conclusions. In children from day-care centers with mild gastroenteritis, the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea.

The Role of Mycobacteria Other Than Tuberculosis (MOTT) in Patients with Cystic Fibrosis

The purpose of this study was to estimate the frequency of and evaluate the clinical impact of pulmonary mycobacterial infections among cystic fibrosis (CF) patients. 185 CF patients aged 2.2-38.5 years were screened by sputum samples and by intracutaneous skin tests against tuberculin and sensitins produced from Mycobacterium chelonae subsp. abscessus, M. avium, M. intracellulare and M. scrofulaceum (the MAIS complex). The skin tests towards the sensitins in BCG-vaccinated patients (n = 60) were significantly influenced by the vaccination. 26 of the remaining 125 non-vaccinated patients had > or = 1 positive skin test (95% confidence limits 15-29%). The majority reacted against the MAIS complex. However, the reactions were similar to those of healthy siblings and an age-matched control group. Moreover, the lung function, growth and HbA1c were similar among skin test positive and negative patients. Three patients had repeated positive sputum cultures, the point prevalence being 1.6% (M. intracellulare, n = 2 and M. chelonae subsp. abscessus, n = 1). During the subsequent 4 years, 4 additional patients with M. chelonae subsp. abscessus were identified. Based on clinical observations, 5 of the infected patients were considered asymptomatic, while 2 might have been symptomatic. In 1 patient, M. chelonae subsp. abscessus disappeared spontaneously. Despite intensive treatment with new antibiotics against Mycobacteria Other Than Tuberculosis (MOTT) in 4 patients, the mycobacteria were not eradicated. In conclusion, MOTT infection was rare and the clinical impact difficult to prove. Treatment should focus on clinical improvement in the individual patient suspected of suffering from significant symptomatic infection. Eradication of the bacteria should not be expected.

Age related standards for total lymphocyte, CD4+ and CD8+ T cell counts in children born in Europe

Objective: Currently used reference values for immunologic markers in children are largely derived from cross-sectional data from historic, small sample size studies in predominantly white children. There is a lack of reliable age-related standards for immunologic markers, such as CD4+ cell counts, in particular in black children whose values according to recent reports may differ from those in white children. Standards are essential for diagnosing and monitoring childhood diseases such as pediatric human immunodeficiency virus (HIV) infection. Design: Prospective cohort study with data on 1781 uninfected children born to HIV-infected mothers in the European Collaborative Study. Methods: Age-related standards (centiles) for immunologic markers (CD4+ and CD8+ cell counts and total lymphocyte counts) up to 5 years in black and up to 10 years in white children were constructed using Generalized Additive Models for Location, Scale and Shape method, which allows for variability and skewness of the data. The optimal model was chosen according to the Akaike Information Criterion. Results: Patterns and values of total lymphocyte, CD4+ and CD8+ cell counts varied with age, especially in the first 3 years of life, but less so thereafter. Values of all 3 immunologic markers were substantially and significantly lower in black than in white children of the same age. Conclusions: We present age-related standards separately for black and white children to aid clinicians in the monitoring of childhood diseases. These standards may also contribute to the decision on an accurate cutoff for CD4+ cell counts for initiating treatment of HIV-infected children.

Maternal Smoking during Pregnancy Increases the Risk of Postnatal Infections in Preterm Neonates

Background: Maternal smoking during pregnancy is known to be associated with perinatal complications such as preterm delivery, low birth weight, and sudden infant death syndrome. Objective: The purpose of this study was to evaluate the influence of smoking during pregnancy on the risk of postnatal infections in preterm neonates. Method: We examined 80 preterm infants (gestational age 24–36 weeks), of whom 40% had been exposed to tobacco smoking during pregnancy. Results: Infections occurred in 31 infants. Gestational age and maternal smoking had a significant effect on the occurrence of infections (p < 0.001 and p = 0.015, respectively). An increase in maternal tobacco consumption by 10 cigarettes/day showed an odds ratio of 2.7 (95% confidence interval 1.1–6.4) for occurrence of infections. Conclusions: A significant association between maternal use of tobacco and the occurrence of infections in preterm neonates was found. Thus, campaigns about the damaging effects of tobacco are still warranted.

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk

Aim: To examine the size of the thymus in uninfected infants born to HIV‐positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. Methods: The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti/weight‐ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HIV‐infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula‐fed infants. Results: At birth the Ti was reduced in infants born to HIV‐infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w‐ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23.8 and the mean Ti/w‐ratio was 4.2. Compared with those of exclusively breastfed infants, the Ti and Ti/w‐ratio of infants fed donor milk were significantly reduced (p < 0.01). The Ti/w‐ratio increased in donor‐milk‐fed infants compared with that in the formula‐fed infants (p= 0.02).

Demographics in HIV-infected children in Denmark: Results from the Danish Paediatric HIV Cohort Study

We present the demographic data on HIV-infected children from the Danish Paediatric HIV Cohort Study, an observational database on HIV in Denmark. Up to 1 July 2003 a total of 89 children had been diagnosed with HIV infection before the age of 16 y, of which 12 (13.5%) had died, 2 (2.2%) had emigrated from Denmark, and 13 had reached the age of 16 y. Estimates of prevalence and incidence of HIV infection in the area were 5.77/100,000 and 0.39/100,000 respectively, which are lower than in the adult population. After 1993 the number of newly diagnosed HIV infected children remained quite constant with an average of 4.2 diagnoses per y. Of the enrolled patients only 15.7% had both their parents of Danish origin, while 58.5% had at least 1 of the parents from an African country. Of the entire cohort, 20% were Caucasians, 51% were males and 76% were infected perinatally. There has been a shift in the HIV epidemic in children over recent y, with a higher proportion of newly diagnosed HIV patients having contracted the infection perinatally, a higher proportion being of non-Caucasian race, and the newly diagnosed individuals being younger. Even since 1995, a major part of the newly diagnosed children was born in Denmark by mothers from high-endemic areas and we therefore suggest that HIV-testing should actively be offered to all pregnant women coming from these high-risk areas.

Childhood Tuberculosis in a Scandinavian Metropolitan Area 1984-93

This study was undertaken to describe the epidemiology, clinical manifestations and prognosis of childhood tuberculosis in Copenhagen, with special attention to differences between Danish children and children of foreign origin. From 1984-93, 66 children, aged 0-14 years, in the Copenhagen area were notified for tuberculosis. More than two-thirds of the children of foreign origin, including 5 patients from Greenland, who were transferred to Denmark for treatment. A close adult contact with contagious tuberculosis was identified in only a few patients born to foreign parents, but more than one-third had travelled to their homeland within 1 y prior to diagnosis. 48 patients (73%) were reported to have only respiratory tuberculosis. Tuberculosis located in cervical lymph glands was the most frequent nonrespiratory manifestation, but was found only in children of foreign origin. Five patients had meningitis. The high incidence among foreign children reflects the incidence in their home countries, but poorer and more crowded living conditions among ethnic minorities in Denmark may also facilitate transmission of tuberculosis. Severe manifestations of tuberculosis still occur, even in a low incidence country.

Fluoroquinolones in the Treatment of Cystic Fibrosis

SummaryCystic fibrosis patients suffer from recurrent and chronic lung infections mainly caused by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The fluoroquinolones, notably ciprofloxacin and ofloxacin, represent an important addition to the therapy of P. aeruginosa infections. They offer the possibility of effective oral treatment for early colonisation as well as chronic infections, even in children. They are associated with only few and mild adverse effects. Development of resistance represents an increasing problem.