Ahmed R. Alsuwaidi

Foscarnet salvage therapy for acyclovir-resistant varicella zoster: report of a novel thymidine kinase mutation and review of the literature.

The authors describe an acyclovir-resistant varicella zoster virus infection in a pediatric patient after hematopoietic stem cell transplant, the use of foscarnet as salvage therapy, and review the literature to clarify the pediatric experience with foscarnet in this setting. A novel thymidine kinase mutation is described, along with a new phenotypic assay for characterizing acyclovir resistance in varicella zoster virus.

Seroprevalence of measles, mumps, rubella, varicella–zoster and hepatitis A–C in Emirati medical students

BackgroundThe aims of this study were to assess the seroprevalence of vaccine-preventable infections in Emirati medical students, and to provide scientific evidence for implementation of a cost-effective immunization guideline and policy for medical school admission.MethodsThis prospective cohort study involved 261 (61% female) Emirati medical students (preclinical and clinical) attending the College of Medicine and Health Sciences at UAE University. Data on vaccination and history of infectious diseases were collected from participants. Blood samples were collected between July 1, 2011 and May 30, 2012 for serological testing and QuantiFERON®-TB assay.ResultsAll students tested negative for infection with hepatitis C virus and human immunodeficiency virus. The prevalence of seropositivity to rubella virus was 97%, varicella–zoster virus 88%, mumps virus 84%, measles virus 54%, hepatitis B virus (HBV) 48%, and hepatitis A virus 21%. The QuantiFERON®-TB test was positive in 8% and indeterminate in 2%. Forty percent of students received HBV vaccine at birth; their HBV titers (mean ± SD) were 17.2 ± 62.9 mIU/mL (median = 1.64). The remaining 60% received it at school and their titers were 293.4 ± 371.0 mIU/mL (median = 107.7, p = 0.000).ConclusionAbout 50% of students were susceptible to HBV and measles virus; therefore, pre-matriculation screening for antibodies against these viruses is highly recommended. Moreover, tuberculosis screening is necessary because of the high influx of expatriates from endemic areas. Students with inadequate protection should be reimmunized prior to contact with patients.

The use of an interferon-gamma release assay to screen for pediatric latent tuberculosis infection in the eastern region of the Emirate of Abu Dhabi

OBJECTIVES Intense migration to the United Arab Emirates from tuberculosis (TB) high-endemic areas presents a particular risk to the population. Screening for latent tuberculosis infection (LTBI) usually involves risk assessment, the tuberculin skin test (TST), and interferon-gamma release assay (IGRA). This study investigated the use of an IGRA to screen for LTBI and compared its performance with a risk assessment questionnaire. METHODS This prospective cross-sectional study was conducted at seven Ambulatory Healthcare Services facilities in Abu Dhabi. Participants (88% Emiratis) were pediatric patients presenting for routine care. The QuantiFERON-TB Gold In-Tube test was performed and the parents completed a questionnaire assessing TB risk factors. RESULTS Six-hundred and ninety-nine subjects (median age 8.7 years, interquartile range 9.2 years) were enrolled; 669 (96%) agreed to testing. Four patients had a positive IGRA; one had previously been treated for TB, resulting in three patients with LTBI. The estimated LTBI prevalence was 0.45% (95% confidence interval 0.09-1.3). A household contact from a TB high-endemic area was reported in 44%, travel to a TB high-endemic area in 10%, and contact with someone with a chronic cough in 7%, a TB case in 3%, a TST-positive case in 2%, and an IGRA-positive case in 2%. Fifty percent of participants had at least one risk factor. The risk assessment did not predict a positive IGRA. CONCLUSIONS The questionnaire yielded a risk of TB exposure of 50%, however the LTBI prevalence, as defined by the IGRA, was low (0.45%).

Cellular bioenergetics, caspase activity and glutathione in murine lungs infected with influenza A virus

Inhibition of cellular respiration, oxidation of glutathione and induction of apoptosis have been reported in epithelial cells infected in vitro with influenza A virus (IAV). Here, the same biomarkers were investigated in vivo by assessing the lungs of BALB/c mice infected with IAV. Cellular respiration declined on day 3 and recovered on day 7 post-infection. For days 3-5, the rate (mean±SD) of respiration (µMO2min(-1)mg(-1)) in uninfected lungs was 0.103±0.021 (n=4) and in infected lungs was 0.076±0.025 (n=4, p=0.026). Relative cellular ATP (infected/uninfected) was 4.7 on day 2 and 1.07 on day 7. Intracellular caspase activity peaked on day 7. Cellular glutathione decreased by ≥10% on days 3-7. Lung pathology was prominent on day 3 and caspase-3 labeling was prominent on day 5. IAV infection was associated with suppression of cellular respiration, diminished glutathione, and induction of apoptosis. These functional biomarkers were associated with structural changes noted in infected mice.

In vitro biocompatibility of calcined mesoporous silica particles and fetal blood cells

Background: The biocompatibility of two forms of calcined mesoporous silica particles, labeled as MCM41-cal and SBA15-cal, with fetal blood mononuclear cells was assessed in vitro. Methods and results: Fetal mononuclear cells were isolated from umbilical cord blood and exposed to 0.5 mg/mL of MCM41-cal or SBA15-cal for several hours. Transmission electron micrographs confirmed the presence of particles in the cytosol of macrophages, neutrophils, and lymphocytes without noticeable damage to the cellular organelles. The particles (especially MCM41-cal) were in close proximity to plasma, and nuclear and mitochondrial membranes. Biocompatibility was assessed by a functional assay that measured cellular respiration, ie, mitochondrial O2 consumption. The rate of respiration (kc, in μM O2 per minute per 107 cells) for untreated cells was 0.42 ± 0.16 (n = 10), for cells treated with MCM41-cal was 0.39 ± 0.22 (n = 5, P > 0.966) and for cells treated with SBA15-cal was 0.44 ± 0.13 (n = 5, P > 0.981). Conclusion: The results show reasonable biocompatibility of MCM41-cal and SBA15-cal in fetal blood mononuclear cells. Future studies are needed to determine the potential of collecting fetal cells from a fetus or neonate, loading the cells in vitro with therapeutic MCM41-cal or SBA15-cal, and reinfusing them into the fetus or neonate.

Bioenergetics of murine lungs infected with respiratory syncytial virus

BackgroundCellular bioenergetics (cellular respiration and accompanying ATP synthesis) is a highly sensitive biomarker of tissue injury and may be altered following infection. The status of cellular mitochondrial O2 consumption of the lung in pulmonary RSV infection is unknown.MethodsIn this study, lung fragments from RSV-infected BALB/c mice were evaluated for cellular O2 consumption, ATP content and caspase activity. The disease was induced by intranasal inoculation with the RSV strain A2 and lung specimens were analyzed on days 2–15 after inoculation. A phosphorescence O2 analyzer that measured dissolved O2 concentration as a function of time was used to monitor respiration. The caspase-3 substrate analogue N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspases.ResultsO2 concentration declined linearly with time when measured in a sealed vial containing lung fragment and glucose as a respiratory substrate, revealing its zero-order kinetics. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Cellular respiration increased by 1.6-fold (p<0.010) and ATP content increased by 3-fold in the first week of RSV infection. Both parameters returned to levels found in uninfected lungs in the second week of RSV infection. Intracellular caspase activity in infected lungs was similar to uninfected lungs throughout the course of disease.ConclusionsLung tissue bioenergetics is transiently enhanced in RSV infection. This energy burst, triggered by the virus or virus-induced inflammation, is an early biomarker of the disease and may be targeted for therapy.

Lung tissue bioenergetics and caspase activity in rodents

BackgroundThis study aimed to establish a suitable in vitro system for investigating effects of respiratory pathogens and toxins on lung tissue bioenergetics (cellular respiration and ATP content) and caspase activity. Wistar rats and C57Bl/6 mice were anesthetized by sevoflurane inhalation. Lung fragments were then collected and incubated at 37°C in a continuously gassed (with 95% O2:5% CO2) Minimal Essential Medium (MEM) or Krebs-Henseleit buffer. Phosphorescence O2 analyzer that measured dissolved O2 concentration as a function of time was used to monitor the rate of cellular mitochondrial O2 consumption. Cellular ATP content was measured using the luciferin/luciferase system. The caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspase activity; cleaved AMC moieties (reflecting caspase activity) were separated on HPLC and detected by fluorescence. Lung histology and immunostaining with anti-cleaved caspase-3 antibody were also performed.ResultsFor Wistar rats, the values of kc and ATP for 0 < t ≤ 7 h (mean ± SD) were 0.15 ± 0.02 μM O2 min-1 mg-1 (n = 18, coefficient of variation, Cv = 13%) and 131 ± 69 pmol mg-1 (n = 16, Cv = 53%), respectively. The AMC peak areas remained relatively small despite a ~5-fold rise over 6 h. Good tissue preservation was evident despite time-dependent increases in apoptotic cells. Lung tissue bioenergetics, caspase activity and structure were deleterious in unoxygenated or intermittently oxygenated solutions. Incubating lung tissue in O2 depleted MEM for 30 min or anesthesia by urethane had no effect on lung bioenergetics, but produced higher caspase activity.ConclusionsLung tissue bioenergetics and structure could be maintained in vitro in oxygenated buffer for several hours and, thus, used as biomarkers for investigating respiratory pathogens or toxins.

Corynebacterium macginleyi Conjunctivitis in Canada

ABSTRACT This report describes for the first time Corynebacterium macginleyi as a cause of conjunctivitis in Canada, where menaquinone analysis was done as part of the strain characterization. This species is typically isolated from ocular surfaces of patients from Europe and Japan. The isolate was resistant to erythromycin and clindamycin.

Seroprevalence of vaccine-preventable diseases among young children in the United Arab Emirates

OBJECTIVES In the United Arab Emirates (UAE), many vaccine-preventable diseases are notifiable and are often reported despite high estimated immunization coverage. The serological assessment of immunity against these infections (serosurveillance) complements disease surveillance (notification). This study aimed to assess the yet unmeasured serological immunities to nine vaccine-preventable infections among vaccinated Emirati children. METHODS This cross-sectional study involved children who attended the Well-Child Care Programme of the Ambulatory Healthcare Services (Al-Ain, UAE) between July 2014 and September 2015. Serological testing was performed in 227 Emirati children (49% females); subjects were aged (mean±standard deviation) 45±14 months (median 43, range 23-71 months). RESULTS The seroprevalence rates varied markedly among the studied vaccine-preventable diseases, ranging from 39.2% (pertussis) to 98.3% (rubella). Other high seroprevalence rates were noted for measles (98.2%) and poliovirus (92%). The seroprevalence rate for mumps was 82.8%, for varicella was 68.3%, for diphtheria was 86.4%, for tetanus was 89.9%, and for Haemophilus influenzae type B was 84.1%. CONCLUSIONS A large number of the studied children had low seroprevalence rates against pertussis, varicella, and mumps. Studies are needed to explore whether modifying the national immunization programme could improve these low seroprevalence estimates.

Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice.

We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4-10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤ 2-week-old C57BL/6 mice following RSV infection. Mice (5-14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1-10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1-10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O2 consumption) and ATP following RSV infection is independent of either age or genetic background of the host.