VPS51 biallelic variants cause microcephaly with brain malformations: A confirmatory report

International audienc

A pooled testing strategy for identifying SARS-CoV-2 at low prevalence

Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups1-7. A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test8. Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30-48-fold dilutions described in previous studies9-11). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).info:eu-repo/semantics/publishe

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm(3) at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population

Oral-genital HPV infection transmission, concordance of HPV genotypes and genital lesions among spouses/ partners of patients diagnosed with HPV-related head and neck squamous cell carcinoma (HNSCC): a scoping review

Abstract Background There is an increase in number of Human Papillomavirus related head and neck squamous cell carcinoma (HPV-related HNSCC) High risk HPV(HR-HPV) types can be cleared by an infected person, however, some can persist and develop HN cancer. There is a broad knowledge gap regarding HPV and related cancers. Main text The aim of this review is to assess existing published knowledge on oral-genital HPV transmission, concordance of HPV genotypes and risk of oral or/and genital lesions among spouses/partners of patients diagnosed with HPV-related HNSCC, identify gaps in the current research and highlight areas that requires further inquiry. Method Database like Pub med, Google Scholar, Scopus, Puplon, Wiley online library were used for search strategy. Published papers on transmission, concordance of HPV genotypes and genital lesions among spouses/partners of patients diagnosed with HPV-related HNSCC were included. Papers published from January1,2000 to October 31, 2022 were included. The published papers included are 8 Case reports, 2 cross-sectional studies, 3 Cohort studies and 2 systematic reviews. Results A total of 2125 citations were retrieved from the five sources. 15papers were included. Case reports reported concurrent HPV-related oropharyngeal, tonsillar, unspecified HNSCC, laryngeal and nasopharyngeal carcinoma among couples. The two cross-sectional studies were done. Almost all the tumors taken from patients with HPV-related oropharyngeal carcinoma (HPV-related OPC) and their spouses were positive for identical HPV 16 type. The three cohort studies showed an increase risk of upper aero-digestive tract cancer among male spouses of females with cervical cancer. Two systematic reviews reviewed literature studies which evaluated concurrent cases of HPV-related Oropharyngeal cancers. Examination of these papers showed that the majority of the studies suggested that there is HPV transmission, concordance and risk of HNSCC cancer among spouses with HPV-related oral-genital cancer. No studies evaluated the risk of developing genital cancer in spouses of patients with HNSCC. Conclusion The findings of this review highlighted big need of further research on oral-genital HPV infection among spouses of patients diagnosed with HPV-related HNSCC. Studies are needed to evaluate the risk of getting genital and upper aero-digestive tract HPV-related cancer among spouses with HPV-related HNC

Array-CGH analysis in Rwandan patients presenting development delay/intellectual disability with multiple congenital anomalies.

BACKGROUND: Array-CGH is considered as the first-tier investigation used to identify copy number variations. Right now, there is no available data about the genetic etiology of patients with development delay/intellectual disability and congenital malformation in East Africa. METHODS: Array comparative genomic hybridization was performed in 50 Rwandan patients with development delay/intellectual disability and multiple congenital abnormalities, using the Agilent's 180 K microarray platform. RESULTS: Fourteen patients (28%) had a global development delay whereas 36 (72%) patients presented intellectual disability. All patients presented multiple congenital abnormalities. Clinically significant copy number variations were found in 13 patients (26%). Size of CNVs ranged from 0,9 Mb to 34 Mb. Six patients had CNVs associated with known syndromes, whereas 7 patients presented rare genomic imbalances. CONCLUSION: This study showed that CNVs are present in African population and show the importance to implement genetic testing in East-African countries

Clinical, cytogenetic and molecular characterization of two cases of mosaic ring chromosome 13.

The occurrence of mosaic ring chromosome 13 is rare. The mechanism of ring chromosome formation is usually associated with loss of genetic material. We report 2 cases of mosaic ring chromosome 13, resulting in deletion of 13qter. The first patient, a 15 year-old boy, presented a delayed psychomotor development, mental retardation, dysmorphic features and bleeding disorders associated with a de novo terminal 13q34 deletion. The second case was a foetus of 31 weeks with prenatal diagnosis of severe malformation such as holoprosencephaly, congenital cardiac defects, gastro-intestinal abnormalities with intrauterine growth retardation, the molecular analysis showed a de novo deletion encompassing the region 13q31.3-q34