HIV-1 transmission through breast-milk: appraisal of risk according to duration of feeding.

OBJECTIVES: To estimate the risk of HIV-1 transmission through breast-milk in children born to infected mothers, and to determine the relationship between duration of breast-feeding and risk. DESIGN AND METHODS: The study population included 168 breast-fed and 793 bottle-fed children born to seropositive mothers. All subjects were enrolled and followed-up in the Italian Register for HIV Infection in Children; HIV sero-status was defined in all children. Multivariate analysis was performed using a logistic regression model. Independent variables included biological factors (duration of breast-feeding, gestational age, clinical condition of mother at delivery, mode of delivery, birth-weight and sex). Year of birth and age when HIV infection was diagnosed were also considered in the analysis attempting to control for possible selection biases. RESULTS: Breast-feeding increased the risk of HIV-1 transmission. The estimated adjusted odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence interval, 1.10-1.28). The infection odds ratio of breast- versus bottle-feeding increased with the natural logarithm of the duration of practice. CONCLUSIONS: These results are the first to provide an appraisal of the additional risk of HIV-1 transmission associated with a seropositive mother breast-feeding her child. Biological significance of this route of transmission was supported by demonstration of a relationship between duration of breast-feeding and risk of HIV-1 transmission.

T-cell subsets and serum immunoglobulin levels in infants born to HIV-seropositive mothers: a longitudinal evaluation.

T-lymphocyte subsets and serum immunoglobulins were assayed in 27 neonates and 12 infants younger than 6 months, all born to HIV-seropositive mothers. No differences in T-lymphocyte subsets between the 27 seropositive and 34 seronegative infants were found at birth. Twelve seroreverted and 14 infected children were followed. CD4+ cell counts were significantly lower in the latter at 3 and 24 months of age. Serum immunoglobulin levels and CD8+ percentages became higher in the infected group, starting from the sixth month, while CD4+ percentages and CD4+/CD8+ ratios became lower, starting from the twelfth month.

Early diagnosis of HIV infection in infants.

Eighteen infants born to anti-HIV-positive mothers were tested bimonthly for immunoglobulin M (IgM) anti-HIV by Western blot and HIV p24 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) in order to determine the role of these markers in the early diagnosis of HIV infection. Twelve healthy infants were also studied as a control group. In 11 out of 18 children (61.1%) an IgM response was demonstrable, in 13 out of 18 (72.2%) IgM anti-HIV and/or p24 antigen (Ag) were detected. Two patterns of IgM response were identified: a precocious IgM positivity (group of five children positive at birth) and a later appearance of IgM, always within the third month (six cases). Early p24 antigenemia occurred in one infant. Three out of four children who developed antigenemia after birth were symptomatic within the sixth month. No clinical or immunological abnormalities were found among the three children who were persistently negative for both IgM anti-HIV and p24 Ag. Serial IgM anti-HIV and p24 Ag testing may be helpful in the early identification of HIV-infected patients.

Acute otitis media in human immunodeficiency virus-infected children.

To evaluate the occurrence and outcome of acute otitis media (AOM) in human immunodeficiency virus (HIV)-infected children, a prospective comparative cohort study was performed. Twenty-seven HIV-infected children were individually matched with paired control subjects and followed up for 543 months (mean 19.4 +/- 11). Data collected were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to Centers for Disease Control classification. During the observation period, 46 episodes of AOM were diagnosed in 15 HIV patients and 22 in 16 control children: 11 P1 had 27 AOM episodes vs 17 in 13 control children; 6 P2 had 19 AOM episodes vs 5 in 4 control children. Human immunodeficiency virus infection does not seem to modify the occurrence of AOM. Recurrent AOM (3 or more episodes in 6 months) was, however, significantly more common in P2 children. Amoxicillin, to which the bacteria isolated in P2 children were sensitive in vitro, cured 33 of 46 episodes in HIV-infected children compared with 20 of 22 in control children. Cure rate was similar in P1 children compared with control children but was significantly lower in P2 versus control children (47.3% vs 100%). Reasons for higher occurrence of failures in P2 children remain to be investigated.

HIV-1 reverse transcriptase codon 215 mutation and clinical outcome in children treated with zidovudine.

OBJECTIVE: In HIV-infected adults prolonged monotherapy with zidovudine may be associated with the appearance of HIV strains with decreased zidovudine sensitivity, owing to specific mutations in the reverse transcriptase (RT) gene, and this has been suggested to be a reason for reduced zidovudine efficacy. This study was undertaken to determine the appearance of mutation at codon 215 of the RT gene in proviral DNA from PBMCs in HIV-infected children. DESIGN: A prospective, open study. SETTING: A University Pediatric Department. PATIENTS AND METHODS: Nineteen HIV-infected symptomatic children were treated with zidovudine for a median of 24 months. Clinical and laboratory controls for HIV infection status were performed monthly. Mutant proviral sequences were evaluated at the start of therapy, every 3 months during the first 6 months of therapy, and every 6 months thereafter. Clinical outcome was defined as stable or deteriorating. RESULTS: No child had proviral sequences mutant at codon 215 before starting zidovudine. Ten of 13 children who had received zidovudine for more than 6 months developed mutant proviral sequences. All the children (10 of 10) with mutant proviral sequences had a deteriorating clinical condition, compared to none of those (0 of 9) without mutation at codon 215. CONCLUSION: The appearance of HIV-1 codon 215 mutation seems to be strongly associated with zidovudine therapy and with clinical progression of HIV disease in children.

Occurrence of infections in children infected with human immunodeficiency virus.

To evaluate the occurrence of infections in asymptomatic and symptomatic human immunodeficiency virus (HIV)-infected children we performed a prospective comparative cohort study. Twenty-seven HIV-infected children were individually matched with paired immunocompetent controls and followed up for a total of 543 months (mean per child, 19.4 +/- 11 months). Collected data were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to the Centers for Disease Control classification. Twenty-seven HIV-infected children had 185 infectious episodes vs. 27 matched controls who experienced 118 infections. P1 children had a number of infections similar to those of normal controls (99 vs. 86) whereas P2 children had a significantly higher number of infections than did controls (86 vs. 32). Pneumonia and oral candidiasis occurred significantly more frequently in symptomatic HIV-infected children than in normal controls. Severe infections occurred almost exclusively in HIV-infected symptomatic children.

Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population.

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 +/- 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HIV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.

Behavioral and psychological disorders in uninfected children aged 6 to 11 years born to human immunodeficiency virus-seropositive mothers.

This study investigated the behavioral and psychological differences between 39 uninfected children born to human immunodeficiency virus (HIV)-seropositive mothers (HIV-seroreverter [SR]) and 78 children with no family history of HIV infection. Caretakers completed the Child Behavior Checklist and the Gittelman modification of the Conners' Parent's Questionnaire, whereas children completed the Children's Manifest Anxiety Scale and the Children's Depression Inventory. In 14 SR children and 28 controls, narrative task was also evaluated. The personalities of SR children, as measured by the caretaker-completed scales, revealed significantly more problems of social adjustment and attention and more externalizing symptoms than did the personalities of control children. On the child-completed scales, SR children showed significantly more anxiety and depression than did controls. Caretakers reported consistently fewer symptoms of anxiety and depression in the children than did the children themselves. Difficulties in verbal recall included aspects of depressive and anxious feelings; on the narrative task measure, SR children showed poorer skill in free verbal recall than did control children, and they simplified episodes with mixed emotions. In addition, ambiguous episodes elicited significantly more negative feelings in SR children than in controls. These findings show that there is a great necessity for assisting SR children. It will be important to determine whether these children will remain at risk for emotional consequences in their adult lives.

[Prolonged Q-T syndrome (Romano-Ward syndrome). Description of a case diagnosed in infancy]. / La sindrome del Q-T lungo (S. di Romano-Ward). Descrizione di un caso diagnosticato nella prima infanzia.

A case of prolonged Q-T interval syndrome without deafness (Romano-Ward syndrome) is reported. A 2-month-old female was seen in consultation because of a near-miss event (syncopal attack). An EKG showed a long Q-T interval. Successful therapy was achieved with propanolol.

C-reactive protein in acute otitis media.

This study was designed to explore whether C-reactive protein (CRP) in serum is helpful in assessing the etiologic diagnosis of acute otitis media (AOM) in children. CRP was measured serially by a radial immunodiffusion method in sera from 67 children with AOM and in 67 matched controls, affected by noninfectious neurologic disorders. In the study group 43 (64%) children had a confirmed bacterial AOM and 24 (36%) showed no bacterial growth from middle ear fluid. The upper limit of CRP in controls was 15 mg/liter. Concentrations of CRP in patients with bacterial AOM ranged from less than 6 to 150 mg/liter; in 71% of the cases the value was greater than 15 mg/liter. In the patients with sterile middle ear fluid CRP ranged from less than 6 to 110 mg/liter; in 67% of the cases the level was greater than 15 mg/liter. CRP greater than 15 mg/liter showed sensitivity of 72%, specificity of 33%, predictive value of a positive test of 66% and predictive value of a negative test of 40%, in detecting bacterial AOM. Measurement of CRP should not be used in the decision regarding antimicrobial therapy for AOM in children.

Amoxicillin twice daily in the treatment of acute otitis media in infants and children.

A total of 110 children with acute otitis media were assigned randomly to treatment with 60 mg/kg per day amoxicillin in a twice-daily (group A) or a thrice-daily (group B) regimen for 10 days. Patients were scheduled for follow-up examinations at mid-treatment, 5 days after the end of therapy and 30, 60, 90 days after starting therapy. At 15 days 6 out of 55 patients (10.9%) treated with amoxicillin twice daily were considered treatment failures compared to 4 children (7.2%) in the thrice daily group. Rates of cure, recurrent otitis media and persistent middle ear effusion were comparable in the two groups of patients at later time intervals. By 90 days the total cure rate was 42.3% (22/52) in children treated twice daily and 41.5% (22/53) in those who had received amoxicillin thrice daily. At the same time persistence of bilateral and unilateral effusion was noted in 12/52 (23.1%) and 8/52 (15.3%) children in group A and in 16/53 (30.1%) and in 10/53 (18.9%) in group B respectively. No significant difference was noted in the two treatment regimens with regard to adverse side effects. Because reduction in division of the amoxicillin dose caused no significant difference in the efficacy of antibiotic treatment of acute otitis media in infants and children, we think that this simplified scheme of therapy can routinely be used in clinical practice and thus improve compliance to antibiotic administration.

Differential development of type 1 and type 2 cytokines and beta-chemokines in the ontogeny of healthy newborns.

Interleukin (IL)-2, interferon gamma (IFN-gamma; type 1 cytokines), IL-4, and IL-10 (type 2 cytokines), and beta-chemokines (MIP-1alpha and RANTES) production by cord blood lymphocytes (CBL) and peripheral blood lymphocytes (PBL) of newborns was analyzed in a cross-sectional study to examine the maturation of these components of the immune response. Immunophenotyping was performed on the same specimens. Results showed that the CD4/CD8 ratio remains stable, the percentage of natural killer cells decreases, and the number and percentage of B cells increase after birth. Analysis of cytokine production suggested that the production of all cytokines increases gradually and steadily after birth, and that IFN-gamma and IL-10 production is reduced at birth whereas IL-2 and IL-4 production is not. Finally, mitogen-stimulated beta-chemokine production was present at birth and increased slightly but significantly with age. These data indicate that a differential functional maturation of immune response after birth favoring a more precocious development of IL-2 (a type 1 cytokine) is present and should help to analyze the ontogeny of the immune system.

Prophylaxis of recurrent acute otitis media and middle-ear effusion. Comparison of amoxicillin with sulfamethoxazole and trimethoprim.

We compared the efficacy of amoxicillin with that of the combination drug sulfamethoxazole and trimethoprim in reducing recurrences of acute otitis media (AOM) in a single-blind, randomized, placebo-controlled trial involving 96 children. Each of the children had had three or more episodes of AOM in the preceding 6 months, and 97% (93/96) of them still had unilateral or bilateral effusion at the beginning of the study. During the 6-month study period, 9 (27%) of 33 of the children in the amoxicillin group developed 9 episodes of AOM, 9 (27%) of 33 of the children in the sulfamethoxazole and trimethoprim group experienced 11 episodes of AOM, and 19 (63%) of 30 of the children in the placebo group developed 25 episodes. Young age and day-care attendance characterized children for whom prophylaxis was more efficacious. Overall persistence of middle-ear effusion was shorter in treated children only as a consequence of the reduced number of new episodes of AOM.

Antibiotic and cholestyramine treatment of chronic diarrhea in HIV-infected children.

BACKGROUND: Chronic diarrhea is a common feature in children infected with human immunodeficiency virus (HIV), and is associated with an increased risk of death in these patients. To describe the effects of an empiric treatment on diarrhea and body weight on HIV-infected pediatric patients. PATIENTS: Eleven vertically HIV-infected children with chronic diarrhea were treated with oral gentamicin, metronidazole and cholestyramine for 3 to 5 days. RESULTS: In children not infected by Cryptosporidium the treatment resulted in a 50% reduction of stool frequency and a 9% increase in body weight. No statistically significant effect was found in children harbouring this parasite. Diarrhea relapsed within 1-2 months in 3/3 children with Cryptosporidium and in 1/8 children without Cryptosporidium (p < 0.05). No untoward side effects from the treatment were observed. CONCLUSIONS: These results suggest that an empiric treatment of this type should be attempted early in HIV-infected children with chronic diarrhea, particularly in those not infected by Cryptosporidium.

Ranitidine pharmacokinetics in newborn infants.

Few data are available for ranitidine pharmacokinetics in the first few days of life. Twenty seven newborn infants were treated with intravenous ranitidine because they were vomiting blood, although they had a negative Apt's test. Each infant provided two blood samples at randomly selected times 30-360 minutes after a 2.4 mg/kg intravenous bolus of ranitidine. A single exponential equation for the concentration-time graph was fitted to the mean serum concentrations at different times. From this model the following mean (SD) measurements wer derived: elimination half life, 207.1 (19.1) minutes; total volume of distribution, 1.52 (0.91) l/kg; and total plasma clearance, 5.02 (0.46) ml/kg/min. Assuming that these measurements do not change with different administered doses, regimens can be derived to assist in planning ranitidine treatment in newborn infants.

Upper GI bleeding in healthy full-term infants: a case-control study.

OBJECTIVE: The aim of this case-control study was to evaluate the frequency and the type of mucosal lesions in newborn babies with upper GI bleeding (UGIB), the diagnostic role and safety of upper GI endoscopy, and the recognition of risk factors associated with the hemorrhagic event. METHODS: A population of 5180 infants born from June, 1988 to May, 1997 was examined. A case was defined as any patient who had UGIB within 4 days of delivery. The diagnosis was made by endoscopic examination in an endoscopy room. The following parameters were determined: amniotic fluid features, funicular blood pH, Apgar index at 5 min, neonatal weight, body length, gestational age, and the presence of other pathologies. Biochemical profiles were also evaluated. Clinical and demographic data of the mothers of the newborn babies were analyzed. Sera of cases and the respective parents were tested for gastrin and pepsinogen. As a control group, 53 full-term healthy infants matched for sex and age were randomly selected from the population of infants born in our pediatric department. RESULTS: Sixty-four of 5180 newborn babies (1.23%) suffered from UGIB within 26.5 +/- 20 h of life. In 53 of 64 cases (mean age = 24.2 +/- 25.5 h) it was possible to carry out an endoscopic examination. In one case, endoscopy was limited to the esophagus because of the presence of multiple mucosal ulcers and substenosis of the viscus. Esophageal damage was observed in 24/53 patients. The esophageal lesions were isolated in nine cases, and occurred jointly with gastric or duodenal damage in 14 cases and one, respectively. Gastric and duodenal lesions were seen in 43/52 and 1/52 patients, respectively. There were 17 cases of gastric ulcers and one case of duodenal ulcer. Blood clots were observed in 14 gastric ulcer patients; in one case there was evidence of active bleeding at the margins of a gastric ulcer. There was no significant difference with regard to the demographic and clinical characteristics of the cases and controls. Median values of serum gastrin of the cases and controls were similar. Median serum pepsinogen was significantly higher in the case group. CONCLUSIONS: UGIB in the newborn babies is often associated with clinically relevant mucosal lesions of the upper GI tract. The evolution, after treatment with antisecretory drugs, is generally rapid and favorable, with clinical recovery usually obtained within 24-48 h. The higher serum pepsinogen levels may only represent a significant risk factor of mucosal lesions and complications.

Impaired response to hepatitis B vaccine in HIV infected children.

Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.

Immunological study in newborns at risk for HIV-1 infection.

We have performed an isoelectric focusing study (IEF) to detect the presence of oligoclonal bands (OB) in serum and in 5 of the correspondent cerebrospinal fluid (CSF) from 14 HIV-seropositive mothers and their newborns. CB were also searched in serum from 4 newborns every 3 months over a period of 12 months. OB were present in 8/14 sera and in 3/3 CSF obtained from the mothers; CSF OB were different from the correspondent serum indicating an intrathecal synthesis. OB were also visualized in serum, but not in CSF, from 3 newborns studied at birth: two of them died respectively at 4 and 5 months of age. One of the 4 newborns that were serially studied showed the appearance of OB at 12 months of age. A comparative study between sera obtained at the moment of delivery from the mother and her newborn showed that oligoclonal banding patterns were superimposable. Our data indicated that: 1) the IgG forming OB in the newborn's serum derive from a passive filtration from mother's serum; 2) the presence of OB seems to be an unfavourable prognostic feature in infants at risk for HIV-1 infection.