Prevalences of herpesviruses DNA sequences in salivary gland biopsies from primary and secondary Sj?gren's syndrome using degenerated consensus PCR primers.

BACKGROUND: Sj?gren's syndrome (SS) is an autoimmune exocrinopathy associated with multiple autoantibodies, lymphocyte infiltration of various organs, and functional deficiency of T cells. Several viruses have been implicated by PCR based studies, but their contribution to the pathophysiology of SS is still controversial. OBJECTIVES: In an attempt to explore the presence of human herpesviruses DNA sequences in salivary glands biopsies from patients suffering of SS, a recently developed strategy based on PCR with consensus degenerated primers that allowed to detect known and eventually unknown herpesviruses was used. STUDY DESIGN: Salivary glands biopsies from 55 patients suffering of primary and SS syndrome were explored by herpesviruses consensus PCR primers and all the PCR products were sequenced. RESULTS: Nine out of 55 salivary glands were positive by PCR and sequence analyses allowed to identify Epstein-Barr virus (EBV) in 6 cases and herpes simplex virus (HSV)-1 in 3 cases. We did not detect any sequences that could be related to a new herpesvirus. CONCLUSION: In view of the good sensitivity of the technique used, our study is not consistent with SS being associated with an unknown herpesvirus. However, our results suggest that EBV and HSV-1 could be implicated in a subset of SS cases and this possibility needs to be explored, to assess the potential benefit of antiviral drugs in some cases.     

Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist treatment-naive patients

Resistance to CCR5 antagonists can be driven by mutations in gp120. Sequences from 323 anti-CCR5 naive patients were analyzed for the presence of previously described in-vivo or in-vitro resistance mutations to CCR5 antagonists located in the V3 loop of gp120. The V3 loop region was rather polymorphic, and 7.3% of patients showed viruses with combinations of mutations in V3 loop previously described to be involved in maraviroc resistance, a licensed CCR5 antagonist.     

Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13 patients with transient neonatal diabetes: new hypothesis raised by the finding of a unique case with hemizygotic deletion in the critical region

Background

Transient neonatal diabetes (TND) is a rare form of diabetes usually present in the first few days after birth that resolves within 1 year but that has a tendency to recur later in life. It can be associated with chromosome 6 paternal uniparental disomy (UPD), paternal duplications or loss of maternal methylation at the 6q24 imprinted locus.

Objective

To report on a cohort of 13 sporadic TND cases, including five with birth defects (congenital abnormalities of heart, brain and bone) and eight without.

Results

The hallmarks of diabetes were similar in patients with or without 6q24 defects. The chromosome 6 abnormalities in our patients (n = 13) included 2 of 13 (approximately 15.4%) cases of paternal UPD6, 2 of 11 (approximately 18%) cases of complete and 3 of 11 (approximately 27%) cases of partial loss of the maternal methylation signature upstream of ZAC1‐HYMAI imprinted genes in non‐UPD cases, and 1 of 13 (approximately 7.7%) cases of hemizygotic deletion.

Conclusion

The deletion was found in a patient with severe congenital abnormalities. This genetic lesion was not reported previously. The hypothesis of an effect on regulatory elements critical for imprinting and tissue‐specific gene expression in early development by the deletion is raised. The data presented here may contribute to the diagnosis and the understanding of imprinting in the region.     

Tracking Demographic Movements and Immunization Status to Improve Children’s Access to Immunization: Field-Based Randomized Controlled Trial

BackgroundCountries’ Expanded Program on Immunization (EPI) contribute to the reduction of mortality and morbidity, but access to these vaccines remains limited in most low-income countries.ObjectiveWe aim to assess whether involving community volunteers (CVs) to track children’s vaccination status and demographic movements and using recorded data to plan catch-up immunization sessions can improve children’s vaccination timeliness, completeness, and coverage.MethodsThis was a field-based randomized controlled trial and communities of the Foumban health district in West Cameroon were allocated to intervention or control groups. In the intervention group, a CV per community was trained to visit households monthly for a year to assess and record in a register, details of EPI-targeted children, their demographic movements and immunization status. The scanned recorded pages were sent to the health center immunization team through WhatsApp and used to organize monthly community catch-up immunization sessions. In the control group, EPI vaccination sessions were routinely conducted. Surveys were conducted at 6 and 12 months from the beginning of the intervention in both study groups to assess and compare immunization timeliness, coverage, and completeness.ResultsOverall, 30 buildings per cluster were surveyed at midline and endline. Of the 633 and 729 visited households in the intervention group at midline and endline, 630 (99.5%) and 718 (98.4%), respectively, consented to participate. In the control group, 507 and 651 households were visited and 505 (99.6%) and 636 (97.7%), respectively, consented to participate. At 12 months intervention, the month one timeliness of bacille Calmette–Guerin (BCG) vaccine did not increase in the intervention group compared with the control group for the age groups 0-11 months (adjusted odds ratio [aOR] 1.1, 95% CI 0.7-1.8) and 0-59 months (aOR 1.1, 95% CI 0.9-1.4), and significantly increased for the first-year BCG vaccine administration for the age group 0-23 months (aOR 1.5, 95% CI 1.1-2.2). The coverage of diphtheria-pertussis-tetanus and hepatitis B+Hemophilus influenzae type B (DPT-Hi +Hb) dose 3 (aOR 2.0, 95% CI 1.5-2.7) and of DPT-Hi+Hb dose 1 (aOR 1.8, 95% CI 1.4-2.4) vaccines increased significantly in the intervention group compared with the control group in the age groups 12-59 months and 12-23 months, respectively. Specific (DPT-Hi+Hb dose 1 to DPT-Hi+Hb dose 3: aOR 1.9, 95% CI 1.4-2.6) and general (BCG to measles: aOR 1.5, 95% CI 1.1-2.1) vaccine completeness increased significantly in the intervention group compared with the control group.ConclusionsFindings support that involving CVs to track children’s vaccination status and demographic movements and using recorded data to plan catch-up immunization sessions improve children’s vaccination timeliness, completeness, and coverage. This strategy should be adopted to improve access to vaccination for EPI target populations and the consistency verified in other contexts.Trial RegistrationPan African Clinical Trials Registry PACTR201808527428720; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3548     

Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in Djibouti

Kaposi's sarcoma herpesvirus (KSHV) is linked causally to Kaposi's sarcoma. Epidemiological studies have shown that KSHV transmission can occur during sex among homosexual men, but heterosexual transmission seems to be very rare in KSHV low prevalence countries. A seroepidemiological study was conducted to determine whether KSHV is transmitted sexually between heterosexuals in an endemic country. Sera from 282 subjects of African origin living in Djibouti were tested for antibodies to KSHV and HIV-1. Among the 282 individuals, 43 were female prostitutes working in the streets (group 1), 123 were female prostitutes working in luxury bars (group 2), 41 were non-prostitute females (group 3), and 75 were non-prostitute males (group 4). KSHV seroprevalence was 26, 20, 17, and 36% in groups 1, 2, 3, and 4, respectively. The seroprevalence of KSHV is not different between street or bar prostitutes and non-prostitute females (OR = 1.67; P = 0.34 and OR = 1.18; P = 0.73). These results suggest that in this endemic country commercial sex work does not seem to be a risk factor for KSHV infection and provides evidence against heterosexual transmission of KSHV in the female population studied.     

Rapid assessment of the HIV/AIDS crisis in racial and ethnic minority communities: an approach for timely community interventions

OBJECTIVES: The US Department of Health and Human Services, in collaboration with the Congressional Black Caucus, created a new initiative to address the disproportionate ongoing HIV/AIDS crisis in racial/ethnic minority populations. METHODS: This initiative included deploying technical assistance teams through the Office of HIV/AIDS Policy. The teams introduced rapid assessment and response methodologies and trained minority communities in their use. RESULTS: The first 3 eligible cities (Detroit, Miami, and Philadelphia) focused assessments in small geographic areas, using multiple methodologies to obtain data. CONCLUSIONS: Data from the first 3 eligible cities provided critical information about changing the dynamics of the HIV/AIDS epidemic at the local level, including program and policy changes and infrastructure redeployment targeted at the most serious social and environmental conditions.     

Clinical validation of saquinavir/ritonavir genotypic resistance score in protease-inhibitor-experienced patients

OBJECTIVE: To identify a genotypic score for resistance to saquinavir boosted with ritonavir (SQV/r; 1,000/100 mg twice daily)-based regimens in protease inhibitor (PI)-experienced patients. METHODS: One-hundred and fifty-one PI-experienced patients receiving a SOV/r-containing regimen were enrolled retrospectively. The virological response (VR) was defined as the decrease in HIV RNA at months 3-5. The effect of each mutation in the protease gene on the VR to SQV/r regimen was assessed using non-parametric univariate analyses and then a step-by-step analysis was carried out using a Jonckheere-Tepstra (JT) nonparametric test to retain the group of mutations most strongly associated with VR. RESULTS: Among the 138 patients with detectable plasma SQV, the median VR was -1.48 [range: -4 to +1.2] log10 copies/ml. Changes at 12 codons were associated with a reduced VR to SQV/r: codons 10, 15, 20, 24, 46, 54, 62, 71, 73, 82, 84 and 90. The JT procedure led to selection of the following genotypic score, 10+15+20+ 24+62+73+82+84+90, as providing the strongest association with VR. In the 35 patients with none of the mutations in this score, the median decrease in HIV RNA was -2.24 log10 copies/ml and it was -1.88 (n=29), -1.43 (n=24), -0.52 (n=30), -0.18 (n=9), -0.11 (n=6) and -0.30 (n=5) log10 copies/ml in those with 1, 2, 3, 4, 5 and 6 mutations, respectively. CONCLUSION: With this resistance score to SQV/r, the isolates were classified as having no evidence of resistance (0-2), possible resistance (3) or resistance (> or =4) by grouping the number of mutations in samples for which the viral load reduction was similar.