Maternal risk factors associated with inadequate testing and loss to follow-up in infants with perinatal hepatitis C virus exposure.

OBJECTIVES: Inadequate testing (IT) and follow-up in infants with perinatal hepatitis C virus (HCV) exposure are challenging. We sought to identify maternal clinical and demographic risk factors that are associated with inadequate testing (IT) and follow-up of perinatally HCV-exposed infants. METHODS: In a retrospective cohort study spanning a period of 23 years, medical records of HCV-infected women and their perinatally exposed infants were reviewed for maternal characteristics that could be associated with their infants' IT and loss to follow-up. RESULTS: A total of 27% (108/407) of HCV-exposed infants were adequately tested (AT) for HCV perinatal transmission. Among AT infants, HCV transmission rate was 11% (12/108). History of maternal intravenous drug use (IVDU) was significantly higher in IT vs. AT infants [88% (193/218) vs. 76% (70/92); p = 0.005]. The percentage of mothers on methadone maintenance treatment during pregnancy was higher in AT vs. IT infants [53% (35/66) vs. 34% (65/186); p = 0.010]. The percentage of mothers with HCV medical care was higher among AT than IT infants [54% (56/102) vs. 41% (106/255); p = 0.022]. CONCLUSIONS: Infants born to HCV-infected mothers have suboptimal testing, possibly leading to an underestimation of the rate of HCV vertical transmission. Infants of mothers receiving HCV medical care and methadone treatment have improved testing. Infants of HCV-positive mothers with history of IVDU have lower rates of testing. Screening HCV-infected pregnant women for history of IVDU and linking them to drug treatment programs, and HCV medical care may improve testing and follow-up in their infants.

Hepatitis C Virus universal screening versus risk based selective screening during pregnancy.

OBJECTIVES: We sought to compare the value of HCV universal screening versus risk-based selective screening in pregnant women. STUDY DESIGN: In a prospective observational study (Jan 2012 - March 2012), pregnant women, in a high risk inner city clinic, who were at "low risk" for HCV infection were tested for HCV antibodies (universal screening) and their medical records were compared to the medical records of pregnant women who were at "high risk" (risk based selective screening as assessed by their obstetricians' screening questionnaire). RESULTS: During the study period, 419 women delivered at our institution with 8.8% (37/419) at high risk for HCV. In 95% (183/193) of available and consenting low risk women, HCV antibody testing was done. The prevalence of HCV was 3.18% (7/220; 95% CI: 1.36-6.50) in all tested women versus 0.95% (4/419; 95% CI: 0.31-2.59) in risk-based selectively tested women. Overall the screening questionnaire had a sensitivity of 0.85 (0.42-0.99) and a specificity of 0.52 (0.45-0.58) in all women who had HCV antibody testing and questionnaire screening. CONCLUSIONS: Using a screening questionnaire to identify women at risk for HCV infection during pregnancy under-estimates the real prevalence of HCV. A universal screening should be considered in high risk cities.

Recurrent Mycobacterium avium osteomyelitis associated with a novel dominant interferon gamma receptor mutation.

Mycobacterium avium causes infections in immunocompromised individuals. Recurrent infection with this organism has been associated with a deletion at the 818 residue of the interferon-gamma receptor (IFN-gammaR). This mutation produces a truncated receptor without an intracytoplasmic tail, resulting in diminished signaling. We describe a substitution at the 832 residue of the IFN-gammaR causing a similar truncated receptor in a 7-year-old girl with recurrent M avium osteomyelitis.

Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media.

OBJECTIVES: To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis. METHODS: In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow-up between Days 22 and 28. RESULTS: Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (13 of 19) [corrected], P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture-positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow-up. CONCLUSIONS: Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM.

Deficient total cell content of CR3 (CD11b) in neonatal neutrophils.

Neonatal neutrophils (PMN) show a well-documented defect in chemotaxis that is associated with several abnormalities of PMN structure and function, including deficient surface expression of CR3 (CD11b), a critical adhesion molecule, on chemoattractant-activated PMN. After activation of PMN with additional stimuli including calcium ionophores, we also found deficient surface CR3 (but normal CR1) expression on neonatal PMN suggesting that abnormal signaling mechanisms are not likely to explain the deficient CR3 expression on activated neonatal PMN. Therefore, we hypothesized that deficient surface expression of CR3 on stimulated neonatal neutrophils is caused by a deficiency in total cell content of CR3. We tested this hypothesis using three different methods to compare the total quantity of CR3 in neonatal versus adult PMN. Western blotting of serial twofold dilutions of PMN lysates from five adult and neonatal pairs, using a monoclonal antibody (MoAb) against CR3 (21PM19C), consistently showed diminished CR3 content in neonatal PMN. A sandwich enzyme-linked immunosorbent assay, in which the CR3 heterodimers in PMN lysates were captured by MoAb to the beta-chain, CD18 (R15.7), then detected with a biotinylated MoAb to the alpha-chain, CD11b (anti-Mac-1), showed that neonatal PMN lysates contain about 66% of adult PMN levels of CR3 (P < 0.03; n = 6). PMN fixed with paraformaldehyde and permeabilized with saponin were studied by immunofluorescence flow cytometry to determine total (surface plus intracellular) CR3 content using phycoerythrin-conjugated MoAb to CR3 (anti-Leu15). Mean total cell CR3 content (in relative fluorescence units) was 58 +/- 14 for adult PMN and 27 +/- 6 for neonatal PMN (n = 5; P = 0.013). In each method, total cell content of CR1 was equivalent for neonatal versus adult PMN. We conclude that neonatal PMN are markedly deficient in total cell CR3 content compared with adult PMN. This result provides a primary explanation for deficient CR3 surface expression on activated neonatal PMN that, in turn, may be important in the chemotactic defect of these cells.

Impairment of chemoattractant-stimulated hexose uptake in neonatal neutrophils.

Neonatal neutrophils (polymorphonuclear leukocytes [PMN]) exhibit a well-documented deficiency in chemotaxis, the nature of which has not been fully elucidated. To determine whether impaired ability of neonatal PMN to increase hexose uptake in response to chemoattractants could contribute to this defect, we compared uptake of 2-deoxy-D-glucose (2-DOG) in stimulated versus resting PMN from neonates (cord blood) and healthy adults. Compared with unstimulated values; N-formyl-methionyl-leucyl-phenylalanine (fMLP) (optimal at 10 nmol/L) caused a threefold to fourfold increase in 2-DOG uptake by adult PMN. Unstimulated 2-DOG uptake by neonatal PMN was slightly higher than that for adult cells, but fMLP caused only a minimal (less than twofold) increase, and optimally stimulated uptake was significantly lower than for adult PMN (P < .01 for adult versus neonatal stimulated uptake; n = 6). Findings were similar when ionomycin or C5a was used as a stimulus. Optimal fMLP stimulation of adult PMN was associated with a marked decrease in the Km for 2-DOG uptake, from 0.74 +/- 0.11 to 0.23 +/- 0.03 mmol/L (delta Km = -0.51 +/- 0.12 mmol/L; n = 6). In contrast, there was relatively little fMLP-induced change in the Km for uptake of 2-DOG by neonatal PMN (from 0.44 +/- 0.04 mmol/L to 0.32 +/- 0.019 mmol/L n = 6); delta Km = -0.12 +/- 0.04 mmol/L; P = .011 for adult versus neonatal delta Km. Stimulation with fMLP was not accompanied by a significant change in the Vmax for 2-DOG uptake with either adult or neonatal PMN, and the respective values for Vmax were similar. We conclude that the chemoattractant-induced increase in hexose uptake by PMN is deficient in neonates compared with adults and that this deficiency involves mechanisms that determine the Km for this process. This impairment may contribute to defective chemotaxis in neonatal PMN.