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There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities., Competing Interests: Declaration of interests E.T., E.C., K.R., J. Button, A.M., M.B., J.A., A.W., M.A., T.K., A.C., S.S.A., D.L.P., and R.J.T. were employees of and stockholders in Illumina, Inc. at the time of this investigation. V.R. is a stockholder in Illumina, Inc. J.O. is a stockholder in Illumina, Inc. and employee of C2N Diagnostics. J. Belmont and T.W. are stockholders in Illumina, Inc. and were compensated as research advisors through Genetics & Genomics Services Inc. C.S. was compensated as a consultant through Genetics & Genomics Services Inc. for statistical analysis. K.M. is an employee of Ambry Genetics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sickle Cell Anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB . The disease severity is very variable and depends on many factors. We evaluated the clinical and biological profile of sickle cell anemia children in rural Central Africa., Methods: This cross-sectional study was conducted in the Hôpital Saint Luc de Kisantu, located 120 km away from Kinshasa-DR Congo in an area of 35 km around Kisantu with a population of roughly 80 000 individuals. We included SCA patients aged 6 months to 18 years. We collected clinical and hematological data. The SCA scoring system proposed by Adegoke et al. in 2013 was applied to determine the disease severity. We searched for factors associated to the disease severity., Results: This study included 136 patients, 66 males and 70 females (sex-ratio M/F 0.94). The mean severity score was 8.21 ± 5.30 (ranges 0-23). Fifty-nine (43.4%) children had mild disease, 62 (45.6%) moderate and 15 (11%) severe disease. Girls had higher levels of HbF than boys ( p  = 0.003). An inverse correlation was observed between fetal hemoglobin and the disease severity ( p  = 0.005, r -0.239, IC 95% -6.139; -1.469). Some factors such age influence the occurrence of certain chronic complications such as avascular bone necrosis., Conclusion: In conclusion, the disease severity of SCA depends on multiple factors. In this study, fetal hemoglobin was the main modulator of the disease severity. These data may also serve as a baseline to initiate HU treatment in this setting.

Introduction: The COVID-19 pandemic prompted a surge in digital public health surveillance worldwide, with limited opportunities to consider the effectiveness or impact of digital surveillance. The news media shape public understanding of topics of importance, contributing to our perception of priority issues. This study investigated news media reports published during the first year of the pandemic to understand how the use and consequences of digital surveillance technologies were reported on., Methods: A media content analysis of 34 high- to low-income countries was completed. The terms "COVID-19," "surveillance," "technologies," and "public health" were used to retrieve and inductively code media reports., Results: Of the 1,001 reports, most were web-based or newspaper sources on the development and deployment of technologies directed at contact tracing, enforcing quarantine, predicting disease spread, and allocating resources. Technology types included mobile apps, wearable devices, "smart" thermometers, GPS/Bluetooth, facial recognition, and security cameras. Repurposed data from social media, travel cards/passports, and consumer purchases also provided surveillance insight. Media reports focused on factors impacting surveillance success (public participation and data validity) and the emerging consequences of digital surveillance on human rights, function creep, data security, and trust., Discussion: Diverse digital technologies were developed and used for public health surveillance during the first year of the COVID-19 pandemic. The use of these technologies and witnessed or anticipated consequences were reported by a variety of media sources worldwide. The news media are an important public health information resource, as media outlets contribute to directing public understanding and shaping priority public health surveillance issues. Our findings raise important questions around how journalists decide which aspects of public health crises to report on and how these issues are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Comer, Donelle, Ngole, Shelley, Kothari, Smith, Shelley, Stranges, Hiebert, Gilliland, Burkell, Cooke, Hall and Long.)

Background : Despite a high incidence of sickle cell anemia, hydroxyurea (HU) treatment is rarely used in the DR Congo. This study aims to assess the efficacy of HU, the incidence of side effects that may limit its use in adults and to determine the dose needed for clinical improvement in patients. Methods : In a prospective study, patients received an initial dose of 15 mg/kg/day which was increased by 5 mg/kg every 6 months, up to a maximum of 30 mg/kg/day. The response and side effects to HU were evaluated biologically and clinically every 3 months during a 2-year period. Results : Seventy adult patients with a moderate or severe clinical phenotype initiated treatment. Only minor side effects were reported. At the end of the 2-year treatment phase, 45 (64.3%) had dropped out, of whom 33 were without a clear reason. Clinical and biological improvement was more marked during the first year. There was a reduction in severe vaso-occlusive crises ( p  < 0.001), need for transfusion ( p  < 0.001), and hospitalization days ( p  = 0.038). Fetal hemoglobin (HbF) levels increased on average 2.9 times after 12 months ( p  < 0.001). The increase in mean corpuscular volume was greater in the first year ( p  < 0.001) than in the second year ( p  = 0.041). The decrease in leukocytes ( p  < 0.001) was significant during the first year. In 70% of patients, the 20 mg/kg/day dose was needed to reach the 20% HbF threshold. Conclusion : HU is effective and well tolerated. The magnitude of the response varies from one patient to another. Improvement of clinical manifestations is achieved in most patients with a relatively low dose. Effective implementation of HU treatment will require improved adherence to treatment., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Throughout the COVID-19 pandemic, a variety of digital technologies have been leveraged for public health surveillance worldwide. However, concerns remain around the rapid development and deployment of digital technologies, how these technologies have been used, and their efficacy in supporting public health goals. Following the five-stage scoping review framework, we conducted a scoping review of the peer-reviewed and grey literature to identify the types and nature of digital technologies used for surveillance during the COVID-19 pandemic and the success of these measures. We conducted a search of the peer-reviewed and grey literature published between 1 December 2019 and 31 December 2020 to provide a snapshot of questions, concerns, discussions, and findings emerging at this pivotal time. A total of 147 peer-reviewed and 79 grey literature publications reporting on digital technology use for surveillance across 90 countries and regions were retained for analysis. The most frequently used technologies included mobile phone devices and applications, location tracking technologies, drones, temperature scanning technologies, and wearable devices. The utility of digital technologies for public health surveillance was impacted by factors including uptake of digital technologies across targeted populations, technological capacity and errors, scope, validity and accuracy of data, guiding legal frameworks, and infrastructure to support technology use. Our findings raise important questions around the value of digital surveillance for public health and how to ensure successful use of technologies while mitigating potential harms not only in the context of the COVID-19 pandemic, but also during other infectious disease outbreaks, epidemics, and pandemics., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Sickle-cell anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB. DNA testing can help to clarify the diagnosis when Hb electrophoresis is inconclusive. We evaluated the usefulness and feasibility of DNA-based diagnosis of SCA in rural Central Africa., Methods: This is a cross-sectional study conducted from November 2016 to end October 2017 in the Hôpital Saint Luc de Kisantu, located 120 km from Kinshasa. This hospital offers the management of SCA patients, mainly identified using the Sickling test (Emmel test) combined with clinical features. We included patients aged 6 months to 18 years locally diagnosed as SCA, and we collected clinical and hematological data. All patients were offered Hb electrophoresis and DNA testing at the Center for Human Genetics of the University of Kinshasa., Results: This study included 160 patients. Hemoglobin capillary electrophoresis suggested that 136 (85%) were homozygote SS, 13 (8.1%) were heterozygote (AS), and 11 (6.9%) were homozygote normal (AA). DNA testing confirmed these electrophoresis findings, with the exception of four patients, two AS in electrophoresis were found SS due to recent transfusion, and two SS in electrophoresis were found AS because they have compound heterozygous form S/β°-thalassemia. The diagnosis of SCA was therefore wrongly ascertained with Emmel test in 15% of patients., Conclusion: This study reveals a high proportion of false-positive SCA diagnoses in a rural environment in Central Africa. This underlines the importance of DNA testing in conjunction with Hb electrophoresis., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Hemoglobin-based tests form the reference diagnostic test for SCA. In limited resource countries, these tests face limitations including cost, low sensitivity due to recurrent transfusions in endemic malaria region, and interference from fetal hemoglobin in neonatal diagnostic. This study aimed at adapting DNA-based SCA tests to limited resource countries and evaluating the economic benefit., Methods: 338 participants were recruited in the Democratic Republic of Congo, sorted in 3 cohorts based on venous blood, umbilical cord blood (UCB) and buccal swab sampling. RFLP was performed to identify mutated allele. The feasibility and technical validity of this RFLP was evaluated for specimens collected on DBS cards and on EDTA tubes. RFLP on DBS stored at room temperature was regularly repeated to assess sample conservation. Finally, the cost analysis was performed., Results: DBS cards yielded identical results to extracted DNA. Repeated testing returned the same result after four years. The DBS-based test performed on UCB or on buccal swab had a sensitivity and a precision of 100%. Cost comparison indicated that our approach costs half price of the widely used isoelectrofocussing of hemoglobin., Conclusion: The implemented DNA-based test approach overcomes the limitations faced by hemoglobin-based tests, while being more affordable. We propose to implement the RFLP test as a first line diagnostic test after transfusion and as second tiers for newborn screening. However, users should be aware that this test is unable to differentiate HbC from HbS or identify other point mutation of gene deletion of HBB gene., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Infectious diseases pose a risk to public health, requiring efficient strategies for disease prevention. Digital health surveillance technologies provide new opportunities to enhance disease prevention, detection, tracking, reporting and analysis. However, in addition to concerns regarding the effectiveness of these technologies in meeting public health goals, there are also concerns regarding the ethics, legality, safety and sustainability of digital surveillance technologies. This scoping review examines the literature on digital surveillance for public health purposes during the COVID-19 pandemic to identify health-related applications of digital surveillance technologies, and to highlight discussions of the implications of these technologies., Methods and Analysis: The scoping review will be guided by the framework proposed by Arksey and O'Malley and the guidelines outlined by Colquhoun et al and Levac et al . We will search Medline (Ovid), PsycInfo, PubMed, Scopus, CINAHL (EBSCOhost), ACM Digital Library, Google Scholar and IEEE Explore for relevant studies published between December 2019 and December 2020. The review will also include grey literature. Data will be managed and analysed through an extraction table and thematic analysis., Ethics and Dissemination: Findings will be disseminated through traditional academic channels, as well as social media channels and research briefs and infographics. We will target our dissemination to provincial and federal public health organisations, as well as technology companies and community-based organisations managing the public response to the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Skin manifestations are common clinical features among HIV/AIDS-positive patients. Their frequencies, patterns and associated factors have been shown to vary from region to region. The present study is aimed at documenting skin manifestations and their relationships with CD4 cell counts among HIV/AIDS patients in Cameroon., Methods: This study lasted for 16 months (from September 2001 to December 2002). After informed consent, data on skin disorders, HIV status, CD4 and viral load were obtained by physical examination and laboratory methods., Results: Of the 384 subjects studied, 236 (61.5%) were females and 148 (38.5%) were males. Up to 264 (68.8%) patients presented with at least one type of skin problem. Generalized prurigo, oral candidiasis, herpes zoster, and vaginal candidiasis were the most common skin problems. Mean CD4 cell count (128 +/- 85 cells/mm(3)) and mean viral load (79,433 copies/mL) in patients with herpes zoster were higher (P < 0.001). Patients with oral candidiasis and vaginal candidiasis had significantly lower (109 +/- 127 cells/mm(3), P < 0.02) and higher (131 +/- 85 cells/mm(3), P < 0.05) mean CD4 cell counts, respectively. Prurigo was associated with higher mean viral load (31,623 +/- 20 copies/mL, P < 0.04). Viral lesions were associated with high mean CD4 cell count (123 +/- 83 cells/mm(3), P < 0.001). Kaposi's sarcoma and parasitic lesions (crusted scabies) were both, respectively, associated with lower mean CD4 cell counts [(78 +/- 66 cells/mm(3), P < 0.001) (6 +/- 0 cells/mm(3), P < 0.04)]., Conclusion: We conclude, first that skin problems are common in HIV-infected individuals in Cameroon and that patients with advanced stages of these problems have relatively very low mean CD4 cell counts. Second, that mucocutaneous disorders like vaginal candidiasis and herpes zoster occur early in HIV infection while Kaposi's sarcoma is common in advanced HIV infection.