Head ultrasound, CT or MRI? The choice of neuroimaging in the assessment of infants with congenital cytomegalovirus infection

Abstract Background Despite growing interest in universal screening for congenital CMV infection (cCMV), and data to support treatment for cases with central nervous system (CNS) involvement, there is limited regarding the optimal imaging modalities to identify CNS involvement. The objective of this study was to assess the concordance between head ultrasound (US) and magnetic resonance imaging (MRI) or computed tomography (CT), in identifying neurological abnormalities in infants with cCMV infection, and to determine whether the addition of advanced neuroimaging after US had an impact on clinical management. Methods Retrospective review of infants with cCMV infection, referred to the Centre d’Infectiologie Mère-Enfant (CIME) at Sainte-Justine Hospital Center in Montreal, between 2008 and 2016. Only patients who underwent head US followed by and brain MRI or CT scan were included in this analysis. Results Of 46 cases of cCMV identified during the study period, 34 (74%) had a head US followed by MRI (n = 28, 61%), or CT scan (n = 6, 13%). In the majority of cases (n = 24, 71%), both images were concordant (11 both reported abnormal, 13 both reported normal). In 5 cases, US was reported normal and subsequent imaging (MRI = 4, CT = 1); reported abnormal. In all 5 cases patients were clinically symptomatic and met treatment criteria even in the absence of neuroimaging findings. In 5 cases, US was reported abnormal with a subsequent normal MRI (4) or CT (1); in 2 of these cases, patients were clinically symptomatic and met treatment criteria regardless of neuroimaging findings. However, in 3 cases, the patients were clinically asymptomatic, and in 2 of these cases, treated based only on the abnormal US findings. Conclusions In this study, we found that that sequential US and MRI were concordant in the majority (71%) of cases in detecting abnormalities potentially associated with cCMV infection. While the addition of MRI to baseline head ultrasound did not influence the decision to treat in clinically symptomatic infants, the addition of MRI to infants with abnormal HUS imaging who are clinically asymptomatic could help refine treatment decisions in these cases

Linking susceptibility to infectious diseases to immune system abnormalities among HIV-exposed uninfected infants

HIV-exposed uninfected (HEU) infants experience increased overall mortality from infectious causes when compared to HIV-unexposed uninfected (HU) infants. This is the case in both the resource-rich and resource-limited settings. Here, we explore the concept that specific types of infectious diseases that are more common among HEU infants could provide clues as to the potential underlying immunological abnormalities. The most commonly reported infections in HEU vs. HU infants are caused by encapsulated bacteria, suggesting the existence of a less effective humoral (antibody, complement) immune response. Decreased transplacental transfer of protective maternal antibodies has consistently been observed among HEU newborns, suggesting that this may indeed be one of the key drivers of their susceptibility to infections with encapsulated bacteria. Reassuringly, HEU humoral response to vaccination appears to be well conserved. While there appears to be an increase in overall incidence of acute viral infections, no specific pattern of acute viral infections has emerged; and although there is evidence of increased chronic viral infection from perinatal transmission of hepatitis C and cytomegalovirus, no data exist to suggest an increase in adverse outcomes. Thus, no firm conclusions about antiviral effector mechanisms can be drawn. However, the most unusual of reported infections among the HEU have been opportunistic infections, suggesting the possibility of underlying defects in CD4 helper T cells and overall immune regulatory function. This may relate to the observation that the immunological profile of HEUs indicates a more activated T cell profile as well as a more inflammatory innate immune response. However, both of these observations appear transient, marked in early infancy, but no longer evident later in life. The causes of these early-life changes in immune profiles are likely multifactorial and may be related to in utero exposure to HIV, but also to increased environmental exposure to pathogens from sicker household contacts, in utero and postnatal antiretroviral drug exposure, and, in certain circumstances, differences in mode of feeding. The relative importance of each of these factors will be important to delineate in an attempt to identify those HEU at highest risk of adverse outcomes for targeted interventions.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Quantiferon Gold-in-tube assay for TB screening in HIV infected children: influence of quantitative values

Abstract Background HIV infected children are at increased risk of TB disease and require annual TB screening. Data on use of IGRA for TB screening in them are limited. We retrospectively evaluated the usefulness of Quantiferon Gold-in-tube test (QFT), an IGRA in screening for LTBI in relatively healthy, immunologically stable HIV infected children. Methods HIV infected children with no prior history of TB were screened for latent TB as part of routine care. They underwent risk of TB assessment, TST and QFT. QFT was repeated twice or three times depending on the quantitative values. Independent test validation was also performed. Results Eighty one children had 109 QFT tests. All had adequate mitogen responses. The initial QFT was positive in 15 (18.5%) children; quantitative IGRA responses were 0.35-1.0 IU/mL in 9 (60%), 1.0-10 IU/mL in5 (33.3%) and >10 IU/mL in 1 (6.7%). None that tested positive had documented TB exposure or TB disease. Baseline characteristics in the QFT positive and negative groups were similar. Repeat testing within 17 weeks demonstrated reversion to negative in 79% of cases. Repeat blinded independent testing of all QFT positive results and a random selection of initial negative tests demonstrated concordance in 96% of cases. Seven children (QFT > 1.0 IU/mL or positive TST) were offered INH preventive therapy. In no case has TB disease developed in 2 years of close follow-up. Conclusions QFT is a valid method for LTBI screening relatively healthy, immunologically stable HIV infected children. However, reversion to negative on repeat testing and lack of correlation with TST results and risk of TB exposure makes interpretation difficult

Studies on the Changes in Lipid Peroxidation and Antioxidants in Fishes Exposed to Hydrogen Sulfide

In the present aquarium study, Oreochromis mossambicus Peters were exposed to two different concentrations of hydrogen sulfide (H2S) (4.9 and 6.6 mg/l), and the changes in lipid peroxidation (LP) products and antioxidants in test fishes were determined in time intervals of 12, 24, 48, 72, and 96 hours. The results showed that with respect to the H2S concentration and duration of exposure, alterations were observed in the concentration of LP products and antioxidants in the various organs of the test fishes. Malondialdehyde (MDA) content increased in the liver, gill, kidney, and brain on exposure to H2S up to 48 hours, and then the MDA content showed steady value up to 98 hours experimental period. Brain and kidney of fishes showed the maximum increase in concentration of reduced glutathione (GSH) on H2S treatment. The gradual decrease in concentration of GSH in the tissues of H2 S-exposed fishes after 48 to 96 hours compared with the control shows the loss of adaptive mechanisms and the oxidation of GSH to glutathione disulphide (GSSG). Slight increase in the activity of GSH-S-transferase and decrease in activity of GSH peroxidase demonstrated the incapability of the vital organs in neutralizing the peroxides generated in the oxidative stress condition

Identifying Clinical Criteria for an Expanded Targeted Approach to Screening for Congenital Cytomegalovirus Infection—A Retrospective Study

Targeted screening for congenital CMV infection (cCMV), which entails CMV testing of infants who fail newborn hearing screening (NBHS), has become common practice. However, this strategy misses nearly all infected infants with normal hearing at birth who are nonetheless at high risk of subsequent hearing loss and would benefit from timely cCMV diagnosis. The objective of this study was to identify expanded criteria predictive of cCMV to increase the scope and utility of targeted newborn CMV screening. In this retrospective study, 465 newborns were tested for cCMV at a single tertiary care center with a targeted screening program between 2014 and 2018. Twenty-two infants were diagnosed with cCMV, representing 0.2% of the 12,189 births over this period and 4.7% of the infants tested. The highest prevalence of cCMV infection was among infants tested because of primary maternal CMV infection (8/42, 19%), followed by failed initial NBHS (10/88, 11.4%), maternal HIV infection (3/137, 2.2%), and clinical suspicion alone (5/232, 2.2%). The symptoms with the highest prevalence of infection among all infants tested included an enlarged liver and/or spleen (33.3%) (3/9), followed by petechiae (33.3%), microcephaly (9.4%), direct hyperbilirubinemia (7.7%), thrombocytopenia (6%), and growth impairment (4.3%). In addition to CMV screening of newborns who fail the NBHS, these data suggest that certain clinical signs of cCMV—in particular: thrombocytopenia, growth impairment, and HIV exposure in pregnancy—should be additional criteria for expanded targeted newborn CMV screening, where universal screening is not yet the standard of care