Zika virus infection during pregnancy and vertical transmission: case reports and peptide-specific cell-mediated immune responses.

Zika virus (ZIKV) infection in pregnant women is associated with birth defects, which are more prevalent and severe the earlier in pregnancy the infection occurs. Pregnant women at risk of possible ZIKV exposure (n = 154) were screened using ELISA for ZIKV IgM and IgG. Nine of 154 (5.84%) pregnant women who underwent screening exhibited positive ZIKV serology. Of these, two maternal infections were confirmed by real-time RT-PCR and five were considered probable, but only three of those were retained for further analysis based on strict diagnostic criteria. Plaque reduction neutralization tests (PRNT) confirmed ZIKV infection in nine cases (5.84%). Two cases of vertical ZIKV transmission were confirmed by PCR. One infant showed no signs of congenital ZIKV syndrome and had a normal developmental profile despite first-trimester maternal infection. In the second case, pregnancy was terminated. Production of interferon γ (IFN-γ) by peripheral blood mononuclear cells obtained from pregnant women and umbilical cord blood was measured using enzyme-linked immunospot assay (ELISpot) after stimulation with panels of synthetic peptides derived from the sequence of ZIKV proteins. This analysis revealed that, among all peptide pools tested, those derived from the ZIKV envelope protein generated the strongest IFN-γ response.

Use of Triple Combination Antiretroviral Therapy With Raltegravir as Empiric HIV Therapy in the High-risk HIV-exposed Newborn.

The recent approval of raltegravir granules for suspension in the newborn population offers a new option for the antiretroviral prophylaxis of newborns for the prevention of perinatal transmission. However, there are little data on its use in preterm infants, nor on outcomes following its use as empiric HIV therapy for newborns subsequently found to be infected. We describe here the use of RAL granules for suspension in these cases.

Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation In Utero Infection.

Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biological mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with human immunodeficiency virus type 1 (HIV-1). The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491 to 1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median-joining network analysis. Compatible with a loose transmission bottleneck, larger numbers of shared HCV variants were observed in the presence of maternal coinfection. Coalescent Bayesian Markov chain Monte Carlo simulations revealed median times of transmission between 24.9 weeks and 36.1 weeks of gestation, with some confidence intervals ranging into the 1st trimester, considerably earlier than previously thought. Using recombinant autologous HCV pseudoparticles, differences were uncovered in HCV-specific antibody responses between coinfected mothers and mothers infected with HCV alone, in whom generalized absence of neutralization was observed. Finally, shifts in HCV quasispecies composition were seen in children around 1 year of age, compatible with the disappearance of passively transferred maternal immunoglobulins and/or the development of HCV-specific humoral immunity. Taken together, these results provide insights into the timing, dynamics, and biologic mechanisms involved in vertical HCV transmission and inform preventative strategies.IMPORTANCE Although it is well established that hepatitis C virus (HCV) can be transmitted from mother to child, the manner and the moment at which transmission operates have been the subject of conjecture. By carrying out a detailed examination of viral sequences, we showed that transmission could take place comparatively early in pregnancy. In addition, we showed that when the mother also carried human immunodeficiency virus type 1 (HIV-1), many more HCV variants were shared between her and her child, suggesting that the mechanism and/or the route of transmission of HCV differed in the presence of coinfection with HIV-1. These results could explain why cesarean section is ineffective in preventing vertical HCV transmission and guide the development of interventions to avert pediatric HCV infection.

Leukocyte telomere length in HIV-infected pregnant women treated with antiretroviral drugs during pregnancy and their uninfected infants.

OBJECTIVES: HIV disease can lead to accelerated telomere attrition, although certain drugs used as part of antiretroviral therapy (ART) can inhibit telomerase reverse transcriptase activity. This could in turn lead to shorter telomeres. We hypothesized that HIV and ART exposure would be associated with shorter leukocyte telomere length (TL) in exposed mother/infant pairs compared with controls. METHODS: In these retrospective and prospective observational cohort studies, TL was evaluated in peripheral blood leukocytes obtained from HIV-infected pregnant women treated with ART and their uninfected infants, and compared with HIV untreated (retrospective cohort) or HIV mothers and their infants (prospective cohort). RESULTS: In HIV-infected ART-exposed mothers, leukocyte TL was not significantly shorter than that in HIV untreated mothers or HIV controls, nor was their infants' TL significantly different. Cord blood of ART-exposed infants exhibited TL shorter than that from infants born to HIV-negative mothers. Placenta also showed evidence of shorter TL after adjustment for relevant covariates. Factors associated with shorter maternal and infant TL included smoking and the use of drugs of addiction in pregnancy. CONCLUSIONS: These results suggest that maternal HIV infection or exposure to ART has minimal effect on infant leukocyte TL, a reassuring finding. In contrast, tissues that express higher telomerase activity such as umbilical cord blood and placenta appear comparatively more affected by ART. Smoking and the use of drugs of addiction have a negative impact on maternal and infant leukocyte TL, possibly through oxidative telomere damage.

Evaluation of a school-based program for diagnosis and treatment of latent tuberculosis infection in immigrant children.

OBJECTIVE: To evaluate a 10-year school-based latent tuberculosis infection (LTBI) screening program, targeting immigrant children in Montreal, Canada, and to identify predictive factors for refusal and, poor adherence to treatment. METHODS: Immigrant children were screened for LTBI with Tuberculin Skin Test (TST). Isoniazid was, given when LTBI was diagnosed. Predictors of LTBI, of refusal of follow-up and treatment and of poor, adherence to isoniazid were analyzed. RESULTS: Four thousand three hundred and seventy-five children were offered screening, 82.3% consented to TST and 22.8% were positive. An, older age at migration (odds ratio (OR)=1 [95% CI: 1.0-1.01]), as well as migration from a none, established market economy country (OR varying from 2.41 to 4.23) were significantly associated with, positive TST. Among positive children, further evaluation was refused in 5.7%, mainly in migrants from, Eastern Europe (OR=4.05 [95% CI: 2.14-7.69]). Refusal of treatment (11.2%) was more frequent in, Eastern European when compared to South-eastern Asian (OR=6.91 [95% CI: 1.56-30.75]), in, blended families (OR=3.25 [95% CI: 1.25-8.46]) and when the first visit to hospital was delayed (OR=1.01 [95% CI: 1.0-1.02]). Adequate completion of treatment was noted in 61.3%. Age>16 years (OR=1.82 [95% CI: 1.82-2.99]), a delay between TST and first visit>15 days (OR=1.6 [95% CI: 1.12-2.28]), as well as the presence of relative>18 years in the household (OR=1.56 [95% CI: 1.0-2.43]), were associated with poor adherence to treatment. CONCLUSION: Sociocultural and behavioural factors are involved in acceptance of LTBI treatment in, immigrant children. Adherence to treatment is challenging and requires comperhension of sociocultural beliefs and accessibility to TB clinic.