Knowledge, attitudes, and practices of primary healthcare practitioners in low- and middle-income countries: a scoping review on genetics.

Individualised treatment, including genetic services, calls for an increased role of primary healthcare practitioners (pHCPs) in diagnosing and caring for individuals with genetic conditions. PHCPs' genetics knowledge and practices must be current to ensure adequate care. A scoping review was conducted to explore peer-reviewed articles on the knowledge, attitudes, and practices (KAPs) of pHCPs concerning genetics, genetic testing, and genetic services. English-language human genetics/genomics articles published between January 1990 and April 2022 in low- and middle-income countries (LMICs) were included. Twenty-eight articles from 16 LMICs in five World Health Organisation (WHO)-defined regions met the inclusion criteria and showed a steady increase in publications, with varied contributions by region. The Eastern Mediterranean Region (EMR) contributed the most articles (n = 8), while the Western Pacific Region (WPR) had the least (n = 2). Brazil published the most articles (n = 6), while ten countries contributed one article each. Fifteen articles included knowledge, 19 included attitudes towards genetics, and eight included genetic practices. The findings indicate that pHCPs in LMICs lack knowledge of genetics and its applications despite their positive outlook towards genetic services. Barriers such as limited resources, financial constraints, and cultural or religious beliefs hinder access to genetic services. Enhancing pHCPs' genetics education is vital for improving care for those affected by genetic conditions. The scarcity of literature in LMICs emphasises the need for research on educational interventions to improve patient outcomes and family support.

A Capacity Audit of Medical Geneticists and Genetic Counsellors in South Africa, 2024: A National Crisis.

Community genetic services were introduced in South Africa almost seven decades ago, with medical geneticists and genetic counsellors being formally recognized for the past 30 years. Initial training platforms were established at academic centres countrywide, and posts for relevant healthcare professionals, including medical geneticists and genetic counsellors were created in the public sector. Despite these early advances, the number of these specialists required to address the rising burden of congenital disorders in the country remains far below required targets established by the National Department of Health. The aim of this study was to analyse the retrospective, current and projected number of medical geneticists and genetic counsellors in South Africa. The results indicate the number of practicing medical geneticists (n = 13) and genetic counsellors (n = 28) are currently at 10% and 5% of capacity targets, respectively. There is unequal distribution of these specialists between the public and private healthcare sectors, and geographical maldistribution. An alarming trend of emigration is particularly prevalent among newly qualified genetic counsellors. With the proportion of congenital disorders expected to continue to rise in coming years, together with the increasing proportion of ageing South Africans, it is imperative that health workforce planning addresses the ever-widening gap between the supply, demand and unmet need for these crucial specialists in South Africa.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020-2023).

Newborn bloodspot screening (NBS) began in the early 1960s based on the work of Dr. Robert "Bob" Guthrie in Buffalo, NY, USA. His development of a screening test for phenylketonuria on blood absorbed onto a special filter paper and transported to a remote testing laboratory began it all. Expansion of NBS to large numbers of asymptomatic congenital conditions flourishes in many settings while it has not yet been realized in others. The need for NBS as an efficient and effective public health prevention strategy that contributes to lowered morbidity and mortality wherever it is sustained is well known in the medical field but not necessarily by political policy makers. Acknowledging the value of national NBS reports published in 2007, the authors collaborated to create a worldwide NBS update in 2015. In a continuing attempt to review the progress of NBS globally, and to move towards a more harmonized and equitable screening system, we have updated our 2015 report with information available at the beginning of 2024. Reports on sub-Saharan Africa and the Caribbean, missing in 2015, have been included. Tables popular in the previous report have been updated with an eye towards harmonized comparisons. To emphasize areas needing attention globally, we have used regional tables containing similar listings of conditions screened, numbers of screening laboratories, and time at which specimen collection is recommended. Discussions are limited to bloodspot screening.

Operational description of rare diseases: a reference to improve the recognition and visibility of rare diseases.

Improving health and social equity for persons living with a rare disease (PLWRD) is increasingly recognized as a global policy priority. However, there is currently no international alignment on how to define and describe rare diseases. A global reference is needed to establish a mutual understanding to inform a wide range of stakeholders for actions. A multi-stakeholder, global panel of rare disease experts, came together and developed an Operational Description of Rare Diseases. This reference describes which diseases are considered rare, how many persons are affected and why the rare disease population demands specific attention. The operational description of rare diseases is framed in two parts: a core definition of rare diseases, complemented by a descriptive framework of rare diseases. The core definition includes parameters that permit the identification of which diseases are considered rare, and how many persons are affected. The descriptive framework elaborates on the impact and burden of rare diseases on patients, their caregivers and families, healthcare systems, and society overall. The Operational Description of Rare Diseases establishes a common point of reference for decision-makers across the world who strive to understand and address the unmet needs of persons living with a rare disease. Adoption of this reference is essential to improving the visibility of rare conditions in health systems across the world. Greater recognition of the burden of rare diseases will motivate new actions and policies to address the unmet needs of the rare disease community.

The Risk of Orofacial Cleft Lip/Palate Due to Maternal Ambient Air Pollution Exposure: A Call for Further Research in South Africa.

Background: Despite being underreported, orofacial cleft lip/palate (CLP) remains in the top five of South Africa's most common congenital disorders. Maternal air pollution exposure has been associated with CLP in neonates. South Africa has high air pollution levels due to domestic burning practices, coal-fired power plants, mining, industry, and traffic pollution, among other sources. We investigated air pollutant levels in geographic locations of CLP cases. Methods: In a retrospective case series study (2006-2020) from a combined dataset by a Gauteng surgeon and South African Operation Smile, the maternal address at pregnancy was obtained for 2,515 CLP cases. Data from the South African Air Quality Information System was used to calculate annual averages of particulate matter (PM) concentrations of particles < 10 µm (PM10) and < 2.5 µm (PM2.5). Correlation analysis determined the relationship between average PM2.5/PM10 concentrations and CLP birth prevalence. Hotspot analysis was done using the Average Nearest Neighbor tool in ArcGIS. Results: Correlation analysis showed an increasing trend of CLP birth prevalence to PM10 (CC = 0.61, 95% CI = 0.38-0.77, p < 0.001) and PM2.5 (CC = 0.63, 95% CI = 0.42-0.77, p < 0.001). Hot spot analysis revealed that areas with higher concentrations of PM10 and PM2.5 had a higher proclivity for maternal residence (z-score = -68.2, p < 0.001). CLP birth prevalence hotspot clusters were identified in district municipalities in the provinces of Gauteng, Limpopo, North-West, Mpumalanga, and Free State. KwaZulu-Natal and Eastern Cape had lower PM10 and PM2.5 concentrations and were cold spot clusters. Conclusions: Maternal exposure to air pollution is known to impact the fetal environment and increase CLP risk. We discovered enough evidence of an effect to warrant further investigation. We advocate for a concerted effort by the government, physicians, researchers, non-government organizations working with CLP patients, and others to collect quality data on all maternal information and pollutant levels in all provinces of South Africa. Collaboration and data sharing for additional research will help us better understand the impact of air pollution on CLP in South Africa.

The burden, prevention and care of infants and children with congenital anomalies in sub-Saharan Africa: A scoping review.

The aim of this scoping review was to determine the scope, objectives and methodology of contemporary published research on congenital anomalies (CAs) in sub-Saharan Africa (SSA), to inform activities of the newly established sub-Saharan African Congenital Anomaly Network (sSCAN). MEDLINE was searched for CA-related articles published between January 2016 and June 2021. Articles were classified into four main areas (public health burden, surveillance, prevention, care) and their objectives and methodologies summarized. Of the 532 articles identified, 255 were included. The articles originated from 22 of the 49 SSA countries, with four countries contributing 60% of the articles: Nigeria (22.0%), Ethiopia (14.1%), Uganda (11.7%) and South Africa (11.7%). Only 5.5% of studies involved multiple countries within the region. Most articles included CA as their primary focus (85%), investigated a single CA (88%), focused on CA burden (56.9%) and care (54.1%), with less coverage of surveillance (3.5%) and prevention (13.3%). The most common study designs were case studies/case series (26.6%), followed by cross-sectional surveys (17.6%), retrospective record reviews (17.3%), and cohort studies (17.2%). Studies were mainly derived from single hospitals (60.4%), with only 9% being population-based studies. Most data were obtained from retrospective review of clinical records (56.1%) or via caregiver interviews (34.9%). Few papers included stillbirths (7.5%), prenatally diagnosed CAs (3.5%) or terminations of pregnancy for CA (2.4%).This first-of-a-kind-scoping review on CA in SSA demonstrated an increasing level of awareness and recognition among researchers in SSA of the contribution of CAs to under-5 mortality and morbidity in the region. The review also highlighted the need to address diagnosis, prevention, surveillance and care to meet Sustainable Development Goals 3.2 and 3.8. The SSA sub-region faces unique challenges, including fragmentation of efforts that we hope to surmount through sSCAN via a multidisciplinary and multi-stakeholder approach.

Parents' perspectives on the use of children's facial images for research and diagnosis: a survey.

Computer-aided facial diagnostic tools are valuable emerging technologies for the early detection and initial diagnosis of congenital disorders. These tools require large datasets of facial photographs, especially of infants and children, to identify these disorders and improve classification accuracies. Researchers need to balance this need for larger datasets with patients' privacy rights, needs and preferences. This study aimed to investigate parents' views regarding the collection, storage, use and publication of their children's facial images for research and diagnostic purposes. A total of 151 parents of children with and without congenital disorders completed an online survey evaluating their views on the collection, storage, use and publication of children's facial images for research and diagnosis. Overall, 72.5% of parents would allow researchers to take facial photographs of their children, preferring the images to be stored in a secure database that is not available to the public. Parents of children with congenital disorders were more accepting of researchers taking facial photographs of their children, compared to parents of children without these conditions. Half of the respondents would allow facial photographs of their children to be published in academic journals, without their eyes covered, and this acceptance increased as the proportion of the child's face covered increased. Parents also indicated specific requirements to allow the use of these images in other similar research studies which need to be taken into consideration when planning studies that involve facial analysis research.

Observed birth prevalence of congenital anomalies among live births at a regional facility in KwaZulu Natal Province, South Africa.

Congenital disorders (CDs), defined as abnormalities in structure or function present at birth, are an important contributor to the disease burden in developing countries. The size and extent of the problem in South Africa (SA) are unknown due to the lack of recent, reliable, observed data on CDs. To address this empirical data gap, this study aimed to measure the birth prevalence of congenital anomalies (a sub-set of CDs) and to describe the pattern of these anomalies at a regional hospital in KwaZulu Natal (KZN), SA. A retrospective, observational, descriptive review of congenital anomalies diagnosed within the neonatal service at Edendale Hospital (EDH), KZN was undertaken between January and December 2018. All EDH in-house live births diagnosed and notified with congenital anomalies by discharge were included. Stillbirths, other pregnancy losses and out-born neonates were excluded. Data were actively collected from the birth register, neonatal admission register, and the individual paper-based surveillance tool developed by the National Department of Health. The in-facility birth prevalence rate for congenital anomalies was 15.57 per 1 000 live births. The most observed system was musculoskeletal (32%) followed by circulatory system anomalies (19%). When the observed birth prevalence rates of key congenital anomalies were compared with previously published, modelled South African data, no significant difference was found. This study responds to the paucity of birth prevalence data on CDs overall and offers evidence that obvious, structural CDs (congenital anomalies) need to be addressed in the SA public health system.

Modelled epidemiological data for selected congenital disorders in South Africa.

Congenital disorders (CD) remain an unprioritized health care issue in South Africa with national surveillance underreporting by > 95%. This lack of empiric data contributes to an underestimation of the CD disease burden, resulting in a lack of services for those affected. Modelling offers estimated figures for policymakers to plan services until surveillance is improved. This study applied the Modell Global Database (MGDb) method to quantify the South African CD disease burden in 2012. The MGDb combines birth prevalence data from well-established registries with local demographic data to generate national baseline estimates (birth prevalence and outcomes) for specific early-onset, endogenous CDs. The MGBd was adapted with local South African demographic data to generate baseline (no care) and current care national and provincial estimates for a sub-set of early-onset endogenous CDs. Access to care/impact of interventions was quantified using the infant mortality rate as proxy. With available care in 2012, baseline birth prevalence (27.56 per 1000 live births, n = 32,190) decreased by 7% with 2130 less affected births, with 5400 (17%) less under-5 CD-related deaths and 3530 (11%) more survivors at 5 years, including 4720 (15%) effectively cured and 1190 (4%) less living with disability. Results indicate a higher proportion of CD-affected births than currently indicated by national surveillance. By offering evidence-based estimates, the MGDb may be considered a tool for policymakers until accurate empiric data becomes available. Further work is needed on key CD groups and costing of specific interventions.

An Overview of Benefits and Challenges of Rare Disease Biobanking in Africa, Focusing on South Africa.

The North-West University's Centre for Human Metabolomics (CHM) is in the process of establishing the first rare disease (RD) biobank in South Africa and Africa. The CHM Biobank's main focus is on the collection of samples and information for rare congenital disorders. Approximately 72% of all RDs have a genetic origin, of which 70% have an exclusive pediatric onset. The need for such a biobank was identified by the CHM diagnostic laboratory. Feedback toward this initiative was overwhelmingly positive at the first stakeholder meeting in August 2019. However, gaining support from the public sector and recruiting of participants have proven to be challenging. Problems experienced to date include lack of support from government and clinicians; lack of knowledge on RDs (patients and clinicians); public health care focus not directed toward RDs; patients not returning for follow-up visits; and unwillingness to participate due to fear of exploitation. The CHM Biobank's vision and goals are aligned to address a national and international research need: it will provide a valuable resource for scientists to improve what is known about these diseases; to better understand the natural history and pathophysiology; to optimize diagnostic methods; and to potentially develop treatments. The genetic variability of the South African population provides added value to the RD biobank. This review provides a brief overview of the literature on the challenges and benefits of an RD biobank and how this relates to low- and middle-income countries (LMIC) like South Africa. The aim of the review is to draw attention to the potential benefits of such an undertaking and to create awareness, at both local and global level, toward some of the unique collective considerations that an RD biobank in LMIC (also unique South African challenges) faces on an operational, collaborate, and sustainability level.

Facial analysis technology for the detection of Down syndrome in the Democratic Republic of the Congo.

Down syndrome is one of the most common chromosomal anomalies affecting the world's population, with an estimated frequency of 1 in 700 live births. Despite its relatively high prevalence, diagnostic rates based on clinical features have remained under 70% for most of the developed world and even lower in countries with limited resources. While genetic and cytogenetic confirmation greatly increases the diagnostic rate, such resources are often non-existent in many low- and middle-income countries, particularly in Sub-Saharan Africa. To address the needs of countries with limited resources, the implementation of mobile, user-friendly and affordable technologies that aid in diagnosis would greatly increase the odds of success for a child born with a genetic condition. Given that the Democratic Republic of the Congo is estimated to have one of the highest rates of birth defects in the world, our team sought to determine if smartphone-based facial analysis technology could accurately detect Down syndrome in individuals of Congolese descent. Prior to technology training, we confirmed the presence of trisomy 21 using low-cost genomic applications that do not need advanced expertise to utilize and are available in many low-resourced countries. Our software technology trained on 132 Congolese subjects had a significantly improved performance (91.67% accuracy, 95.45% sensitivity, 87.88% specificity) when compared to previous technology trained on individuals who are not of Congolese origin (p < 5%). In addition, we provide the list of most discriminative facial features of Down syndrome and their ranges in the Congolese population. Collectively, our technology provides low-cost and accurate diagnosis of Down syndrome in the local population.

Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations.

Advances in omics and specifically genomic technologies are increasingly transforming rare disease diagnosis. However, the benefits of these advances are disproportionately experienced within and between populations, with Indigenous populations frequently experiencing diagnostic and therapeutic inequities. The International Rare Disease Research Consortium (IRDiRC) multi-stakeholder partnership has been advancing toward the vision of all people living with a rare disease receiving an accurate diagnosis, care, and available therapy within 1 year of coming to medical attention. In order to further progress toward this vision, IRDiRC has created a taskforce to explore the access barriers to diagnosis of rare genetic diseases faced by Indigenous peoples, with a view of developing recommendations to overcome them. Herein, we provide an overview of the state of play of current barriers and considerations identified by the taskforce, to further stimulate awareness of these issues and the passage toward solutions. We focus on analyzing barriers to accessing genetic services, participating in genomic research, and other aspects such as concerns about data sharing, the handling of biospecimens, and the importance of capacity building.

The case for the genetic nurse in South Africa.

The care and prevention of congenital disorders (CDs) is an emerging but unprioritised health need in South Africa (SA). Inadequate empirical data and underreporting conceal the true burden of CDs while medical genetic services to confront the problem have regressed. Positive epidemiological transition in the country now demands these services are improved to significantly further reduce child mortality. Current sector capacity in SA is inadequate and required personnel targets will not be reached quickly enough to meet the growing health need even if relevant posts are designated. Historically, genetic-trained nurses played a defined role in primary healthcare (PHC) by recognising and diagnosing common CDs and counselling patients and their families, while referring complex matters to the limited tertiary medical genetic services available. Policy changes to redress past inequalities and other healthcare priorities resulted in genetic services being incorporated into PHC, with few genetic nurses retaining their genetic services role. While the medium- to long-term aim for SA would be to develop medical genetic services with appropriate capacity at all levels of healthcare, there is an urgent short-term need to provide basic medical genetic services in PHC. Central to achieving this is the upgrading and re-implementation of the previously successful Medical Genetics Education Programme (MGEP). This post-graduate distance learning, education programme is implemented with the Congenital Disorders Course Book, a distance education tool promoting independent, home-based learning. Together, these tools offer an approach to swiftly build up a nursing workforce with improved knowledge and skills in medical genetics.

Review of the 2015 Guidelines for Maternity Care with relevance to congenital disorders.

The 4th edition of the Guidelines for Maternal Care in South Africa published by the National Department of Health in 2015 was evaluated with relevance to the care and prevention of congenital disorders (CDs). Disparate terminology is used for CDs throughout the guidelines, and overall less detail is included on CDs compared with the previous edition. This demonstrates a lack of awareness around the growing health need and contribution of CDs to the disease burden in South Africa (SA). Referrals to medical genetic services in the guidelines for mothers of advanced maternal age and other high-risk categories do not take into account the insufficient capacity available for screening and diagnosis of CDs. This highlights the lack of consultation with the medical genetics sector during the development of the guidelines. To respond to the Sustainable Development Goals by 2030, CDs must be integrated comprehensively at all levels of healthcare in SA.

Prevention of Congenital Disorders and Care of Affected Children: A Consensus Statement.

As the Sustainable Development Goals are adopted by United Nations member states, children with congenital disorders remain left behind in policies, programs, research, and funding. Although this finding was recognized by the creation and endorsement of the 63rd World Health Assembly Resolution in 2010 calling on United Nations member states to strengthen prevention of congenital disorders and the improvement of care of those affected, there has been little to no action since then. The Sustainable Development Goals call for the global health and development community to focus first and foremost on the most vulnerable and those left behind in the Millennium Development Goal era. To maximize the opportunity for every woman and couple to have a healthy child and to reduce the mortality and severe disability associated with potentially avoidable congenital disorders and their consequences for the children affected, their families and communities, and national health care systems, we propose priority measures that should be taken urgently to address this issue.