This review aimed to interrogate the published literature for pHCP’s genetic knowledge, attitudes and practices towards genetics and genetic testing in LMIC. To our knowledge, this is the first review of this kind. Over the 32-year period of study (1990-2022) only 28 articles met the inclusion criteria from 16 LMIC countries.
The low number of articles on the knowledge, attitudes and practices of genetics/genetic testing found in this review may be indicative of the limited implementation of genetic services in LMIC. High income countries have been the forerunners in introducing and offering genetic testing for diagnosis and prenatal diagnosis, with research into genetics knowledge of pHCP dating back to 1989 in these countries (16). In comparison, many LMIC lack comprehensive genetic services, reflecting the ongoing epidemiological transition in these countries – a process that was completed in most HIC countries decades ago (17).
Publications overview
Geography
South East Asia Region
Geographically, the highest number of articles meeting the inclusion criteria were identified in SEAR (n=8), emanating from only four of the 11 countries. This may be accounted for, in part, by a group of HCPs with an interest in reproductive and genetic technologies, including TOP, in Sri Lanka, who collectively published three articles over four years (2002-2005) (18-20). The first IVF clinics emerged in the country in 1999, but without accompanying laws or guidelines governing their regulation (18). The authors of these three timeous publications were interested in the effects of these new technologies on reproductive options, especially since Sri Lanka is a multi-cultural and multi-religion country, with various worldviews and ethical concerns. This was followed up by an article by de Silva, Jayawardana (21) who investigated TOP for four genetic conditions in Sri Lanka.
India was another SEAR country with articles published; one on late TOP for fetal anomalies (22) and the other on Huntington’s disease (23). There was then an 8-year gap until Alfaqih, Khader (24) investigated attitudes towards genetics and biochemistry in Jordan. The most recent publication from this region was from Indonesia on attitudes towards genome editing (25). The lack of publications from other countries in the region may be due to a high rate of consanguinity and the general lack of physicians and inadequate genetic education of physicians, who are not trained or empowered to identify and diagnose genetic conditions (26). It may also be indicative of the early stages of epidemiological transition experienced by the countries during this time period, when the diagnosis and management of infectious diseases would have been a greater priority. For example, India was reported to have neither a social healthcare system nor a compulsory healthcare insurance system at the time. Although WHO has frequently emphasised the need for genetic services, with proposed guidelines in all member states (27) the continued lack of financial and human resources and supporting evidence base prevents implementation – particularly in LMIC.
The Region of the Americas
The AMR and EMR were the next most productive regions, with seven articles published in each. In AMR, the majority of articles (n=6) were published in Brazil, plus one in Mexico, which was also the earliest article included in this review in 1999 (28), focusing on predictive and prenatal diagnosis of Huntington’s disease. In that article, they reported that a genetics course was only considered mandatory for completing a medical degree since 1996 at the Medical School of the National Autonomous University of Mexico. They also suggested that specific genetic conditions be managed by genetics units and specialists with greater disease-specific knowledge. This provides context for the lack of genetics-related knowledge/services in the country. No subsequent articles were identified regarding knowledge, attitudes and practices of HCP in Mexico, published in English.
Brazil as an individual country had the highest number of published articles (n=6, 22%) in the review. The earliest article, in 2008, focused on a specific cardiac diagnosis of Brugada syndrome (29), however, three articles were published by different departments of a specific institution, the Federal University of São Paulo (30-32). These focused on HCP awareness of primary immunodeficiencies and competencies in prevention and diagnosis of birth defects. More recent, studies were published by different groups across Brazil (15, 33)with a focus upon the provision of genetic healthcare services. This may be linked to a co-ordinated health strategy in the country in response to the Zika outbreak in the region, which also benefited other conditions, including congenital disorders.
Eastern Mediterranean Region
Seven articles from four of the 16 LMIC countries in the EMR were included. These seven articles included Lebanon (34, 35), Pakistan (36, 37), Iran (38, 39) and the most recent from Syria (40). The topics covered were diverse; one article on attitudes towards termination of pregnancy (34), two on haematological disorders (36, 39), two on the provision of clinical and counselling genetic services (35, 37), and one on HCP's knowledge of PIDs (38). The most recent article from this region focused on the newer developments of pharmacogenomics (40). Countries in the EMR have a higher rate of consanguinity in Arab communities, which has led to a higher frequency of congenital disorders (CD), particularly autosomal recessive conditions (41). Coupled with the views and laws around TOP, research into autosomal recessive and haematological disorders, TOP and the provision of genetic services, provides insight into healthcare services in this region.
Africa
While there are 47 countries in the AFR region, only four produced articles included in this review. Three of the four articles focused on pregnancy and SCD (42-44). SCD is the most common monogenic disorder (45) with a high birth prevalence in SSA(46). In countries such as Cameroon, where there is no universal medical insurance, non-communicable diseases (NCD) such as SCD represent an increasing health burden (43). The carrier rates for SCD are estimated to be around 1 in 4 people (42). Although national control programmes may be partially implemented, care for affected individuals is still lacking (42, 43).
Western Pacific Region
China and Malaysia were the only two countries from 23 LMIC in the region to have articles included in the review (47), (48). It is possible that non-English articles are available from these countries. Both articles discussed pregnancy and prenatal testing; NIPT was not covered by medical insurance in China, resulting in this being unaffordable for many women, while prenatal diagnosis, and treatment, for thalassemia was available at public-funded hospitals in Malaysia. If NIPT was funded by the state in China, this would assist in “decreasing the societal burden of birth defects” in China and contributing towards their national goal (47).
Timing of Publications
During the study period (January 1990 to April 2022), only one article (28) preceded the publication of the human genome in 2000. In the following decade, nine studies were published and a further 18 from 2010 to April 2022. This increase in relevant publications across LMIC is encouraging, particularly individual publications from India, Iran, Lebanon and Malaysia (22, 23, 34, 35, 38, 39, 48), suggesting recognition of the need for clinical genetic services. Many African countries, where there is a high burden of SCD (42-44), have begun to assess the need for HCP and genetic services in primary healthcare, which is ideal for screening, antenatal care and early childhood treatment of genetic conditions.
Qualitative Framework
The thematic framework (Figure 6) developed from the articles was used to contextualise and evaluate the qualitative component of this review.
Lack of knowledge:
With over half of the articles (n=15) incorporating aspects of pHCP knowledge, most reported on the insufficient genetic knowledge of HCP. This lack of knowledge leads to barriers in services due to uncertainty and lack of confidence in treating and referring patients with genetic problems (49). The results of self-rating and/or assessment of knowledge scores implemented in these articles ranged from very knowledgeable, satisfactory and adequate/fair to insufficient (15, 24, 28-31, 37-39, 44). This reported deficit supports the call for continuous educational interventions for the improvement of pHCP’s knowledge (50).
Shortfalls in several areas of genetic knowledge were identified:
Lack of basic genetic knowledge
Both pHCP and nurses were reported as lacking specific genetics knowledge (i.e., as taught in medical school or nursing college). This included: not knowing that genetic conditions could be “prevented”; the availability/option of prenatal screening, and; the inheritance pattern of certain conditions, including how to collect information via a family history (28, 31, 32, 51). A systematic review by Talwar (52) focused on furthering the education of non-genetic specialist HCP found that most studies and interventions on basic genetics knowledge were conducted in the USA, and others were similarly undertaken in Canada, Europe and HICs in Asia. A recent review by Chou, Duncan (53) highlighted strategies to facilitate delivery of genetic testing and services through primary healthcare, again with most studies from HIC only. One article focusing on LMIC was a needs assessment undertaken in Ethiopia by Quinonez, Yeshidinber (51), to evaluate HCP experiences with genetic services, and suggested tools to assist with data collection for epidemiological studies. This study highlighted how clinical genetic services may be supported in LMIC by the introduction of tools to assist pHCP.
Emerging technologies
Applying existing genetics knowledge in primary practice is already a challenge for many pHCP. Genetics and genomics are rapidly developing fields, and pHCP are at risk of being left behind in a genomics era that is becoming increasingly reliant on this knowledge. Staying abreast of newer developments in genetics includes the application of genome editing in newborns, WGS, whole genome association studies and epigenetics (24, 25, 30, 38). Keeping up to date with these and other emerging technologies and the scope and methodologies of available tests is challenging for pHCP, as they are infrequently exposed to genetic conditions in their practices/clinics.
Educational interventions to inform pHCP about new genetic developments will enhance their knowledge, and this may be incentivised by accrediting such interventions as continued professional development (CPD) events.
Referral to Genetic Services
The referral of patients in existing health systems in LMIC is challenging. HCP may be unaware of existing facilities and/or the travelling distances and time required by patients to access these services may be prohibitive. Antoun, Zgheib (35) reported that up to 15% of HCP were unaware of genetic services in their area of practice. It has also been shown that HCP are less likely to order genetic tests if they are unaware of the availability of genetic services (54). This lack of knowledge of services leads to a lack of appropriate care for patients and their families. In Brazil, Iriart, Nucci (15) reported a lack of referral from inland, rural Brazil to the capital cities and urban centres, where genetic services are offered. Transportation challenges and the cost of travel in a resource poor country is a major obstacle for patients and may result in a reluctance by HCP to refer. Decentralisation and expansion of genetic services may contribute to increased access to these services in LMIC.
Clinical Guidelines
Knowledge of and attitudes towards recommendations of the Center for Disease Control (CDC) and other international and national guidelines or a local protocol was found to be poor. Ferreira, Russo Akiba (31) reported that only half of pHCP prescribed folic acid for pregnant women, and only 10% of HCP reported knowledge of the international guidelines for testing for Huntington’s disease (28). This deficit highlights the need for education related to relevant guidelines and recommendations for the management and care of CDs. Such recommendations and guidelines may also be country-specific, for example in Cameroon and central African countries for SCD, or the international guidelines for diagnostic and predictive testing for Huntington’s disease.
Attitudes of Primary Health Care Practitioners
Towards genetic services
Of the 28 included articles, 19 (70%) included a component on attitudes in general, indicating a belief that genetic testing and counselling are important (35) - especially among general practitioners (GPs) and primary care physicians (36). A positive attitude was also noted towards genetic counsellors being incorporated into the healthcare system, with five articles discussing positivity towards obtaining a genetic diagnosis and genetic services in general (24, 28, 32, 36, 37). Supportive attitudes towards genetic counselling, prenatal diagnosis and selective termination of affected pregnancies were also highlighted (44), depending on the specific legislation related to TOP. Overall, positive attitudes were generally related to the potential offered by genetics and genetic testing for the future development of genetic services in LMIC.
In contrast, the findings of Wonkam and Hurst (43) emphasised that genetic services challenge the “power to cure” by HCP, which may create an overall negative attitude towards such services. This suggests that pHCP may feel helpless and uncomfortable caring for patients with incurable genetic conditions, thus impacting on their confidence. Education and psychosocial interventions for HCP are proposed to assist with the perceived emotional burden of caring for affected individuals. HCP should be made aware that parents see HCP’s offering to care for the patient (and their family) may be better than no treatment at all. Other reasons for HCP not accepting genetic services include a mistaken belief that other preventable diseases (mainly infectious) should be treated first, the fear of discrimination, an increase in abortion rates and individual stress (36).
Towards patients with genetic conditions
Insecurity of pHCP related to prescribing medication for patients with genetic conditions was expressed (15). HCP face bureaucratic challenges in accessing appropriate care (medication and nutrition) for their patients (15). This may leave patients and families feeling further stigmatized and unable to access appropriate treatment, together with a reluctance by HCP to care for patients where they are not able to treat appropriately.
Towards new technologies
In general, the articles indicated that most pHCP are positive about the impact of new technologies on genetics and care. They understood the role of genetics in designing better targeted therapies and how the role of specific variants may determine disease susceptibility (24). A similar attitude was noted towards preimplantation genetic diagnosis (PGD). The use of new technologies to overcome infertility was viewed in a positive light (18). A positive attitude towards the implementation of non-invasive pregnancy testing (NIPT) in China was also reported (47), as well as towards genome editing for the purposes of treating fatal or debilitating diseases, at both the embryonic and somatic levels in Indonesia (25).
Negative attitudes were expressed towards genome editing when it was applied to non-health related aspects such as enhancing human ability or performance i.e. eugenic (25). Alfaqih, Khader (24) reported on the diverse views around establishing a DNA database to enhance personalised medicine, and Albitar and Alchamat (40) reported that physicians were uncertain about requesting pharmacogenomics testing before prescribing medication. It is anticipated that as related knowledge increases and application of these genetics tests improves, the attitudes of HCP may change and improve as a result of the expanding evidence base.
Barriers to Genetic Services:
Barriers to developing and accessing genetic services globally have been reported for decades (49). More recently, key barriers to obtaining these services have been outlined as: 1) Lack of knowledge and skills (the focus of this article); 2) Challenges in national healthcare systems; 3) Ethical, legal and social issues (ELSI), and; 4) Lack of an evidence base (7). Additional barriers include poor skills in taking family histories, non-existent referral guidelines and other tools, and a lack of confidence in delivering genetic services (attitudes and skills), time constraints and cost of tests (32, 33, 35, 48).
Specific barriers to genetic services identified in this review include:
Inadequate genetic services
Although the availability of formal genetic services available remains undocumented in many LMIC, an overview of 34 LMIC by Kaur, Hadley (55), indicates that limited genetic services exist in these countries. While anecdotal evidence indicates a lack of clinical genetic services in many LMIC, there is little empiric evidence to support this, particularly in Africa. The Society for the Advancement of Sciences in Africa (SASA) (56) states that clinical genetic services are either non-existent or rudimentary across Africa, except for in South Africa which has a formal training programme to build capacity.
Other, specific challenges in providing genetic services highlighted by this review include:
Capacity:
Many LMIC lack the necessary personnel, technology, infrastructure and capabilities to be able to offer a comprehensive clinical genetics service. (43, 51). For example, in Pakistan there are no genetic counselling services offered by the healthcare system (57), preventing patients with single gene and other congenital disorders from receiving the required counselling to accompany a diagnosis (37, 47). Further service bottlenecks may also be due to a lack of adequate genetic specialists in the country, as reported by Ashfaq, Amanullah (37) in Pakistan.
Capacity issues are compounded by the overall scarcity of relevant clinical specialists, including clinical geneticists, and other relevant specialities. In some LMIC such as Ethiopia, there are no clinical geneticists or genetic counsellors (58). Encouragingly, Abacan, Alsubaie (59) reports on several LMIC that have genetic services provided by genetic counsellors. These include Cuba with 900 genetic counsellors equating to 82 per million, Romania (Europe) with 4 per million, Malaysia has 5 equating to 0.2 per million, the Philippines 0.1 per million (SEAR) and South Africa with 0.4 per million (AFR). A recent article from Brazil reported that 332 medical geneticists for approximately 30% of the 211 million population of (1.6 per million) (60). South Africa is the only country in AFR with both clinical geneticists and genetic counsellors. However, with only 14 medical geneticists (0.2 per million) and 20 genetic counsellors (0,4 per million), capacity remains far below the recommended 120 clinical geneticists (2 per million) (61) for 60 million people. This lack of capacity is emphasised by comparison with the UK, with a similar population size (60 million) where 5 genetic counsellors per million are available. This is a far cry from HIC such as the USA with 12, Canada with 9, and Australia/New Zealand with 7 genetic counsellors per million of the respective populations (59).
To maximise capacity, several alternative, innovative options have been proposed by Mikat-Stevens, Larson (7) to increase access to genetic services, including telehealth and virtual consults. The recent COVID19 global pandemic has made virtual consults a reality for many patients and HCP, including genetic services.
The collective challenges of limited resources, high costs, and a lack of demand for genetic testing (due to a continued focus on infectious diseases in many LMIC), results in many genetic tests being sent abroad. Recently, the focus is being shifted to building local expertise and testing capacity, but this remains an uphill struggle for LMIC when international companies offer equivalent testing at a lower price. In response to this need, the African Society of Human Genetics (AfSHG) and the Human Heredity & Health in Africa (H3Africa) aim to create and build genetic capacity by facilitating genetic research laboratory training at all levels to encourage genetic services and to contribute to patient care (www.afshg.org).
Political Will
For genetic services to be implemented, legislation must first be developed and implemented using appropriately allocated resources. Wonkam and Hurst (43) postulate that a high rate of termination of SCD-affected pregnancies is indicative of the failure of professional stakeholders to provide adequate care in Cameroon. In contrast, in Brazil, national policy has required the integration of genetic services into the primary healthcare (32). This political commitment to genetic services is demonstrated by the number of medical geneticists in the country, as indicated above.
Financial constraints
Inadequate Funding
Seven articles in this review highlighted the challenge of inadequate funding allocated for genetic testing in LMIC (30, 33-35, 37, 44, 47). Most of these countries cannot afford to implement comparable genetic services to those in HIC (51). In LMIC, even basic genetic services are seen as an unnecessary expenditure, and HCP do not consider CDs a priority (33), since the underlying genetic cause cannot be changed and these conditions are considered untreatable (20). Such attitudes, combined with a preference to fund more obvious and “treatable” infectious diseases, results in inadequate budget allocations for genetic services, including genetic testing.
Care for patients and individuals with rare genetic conditions is often costly, and treatment options, if available, are often limited and unaffordable (15). Most state healthcare services in LMIC cannot afford to provide treatment for patients with rare diseases (15, 20). In Cameroon and other African countries, families are expected to pay for hospital bills due to lack of universal health insurance coverage (43).
Out of pocket expenses
Due to a lack of state funding for genetic testing and related services, the financial burden falls upon the patient and their families. For patients with no private medical insurance, the patient or family is expected to pay for the services out of their own pocket. Ashfaq, Amanullah (37) reported that the cost of genetic testing in Pakistan is prohibitive, given the per capita income, unless a new cost model is developed. The example of carrier screening and prenatal screening/testing for specific conditions was highlighted in five countries: Ghana, Lebanon, Pakistan, Brazil and China (15, 35, 37, 44, 47). Pregnant women in Ghana may not be able to access testing for the sickle cell trait, if they are unable to pay for laboratory testing (44). HCP in Lebanon are hesitant to offer genetic counselling due to the cost (35) and in another study in China, 72,5% of HCP believed that women would not undergo NIPT if they had to pay (47). Such studies undertaken in LMIC highlight the additional financial burden of genetic testing placed upon the patient and family, who are rarely able to afford these costs, as well as transport and additional living expenses. These challenges, in part, contributes to the higher burden of congenital disorders and associated mortality and morbidity in LMIC (62).
Religious and cultural beliefs
This review revealed that the diverse cultural and belief systems in LMIC may affect access to specific genetic services, depending on the dominant religion in the country of residence (37). This was specifically highlighted in two topics:
1. Termination of pregnancy
TOP for foetal anomaly is a contentious topic. TOP is not permitted by some religions, and related laws and regulations vary within and between LMIC, limiting options for addressing affected pregnancies (19, 20, 34, 36, 48). de Silva, Jayawardana (21) reported that religious affiliation was the only variable that influenced decisions regarding aspects of TOP in their study. Even following amendments to relevant TOP laws and regulations in some countries, such as in Sri Lanka in 1995 (where TOP was strictly prohibited, but is now allowed when the mother’s life is in danger with supporting signatures from three doctors), TOP for CDs remains controversial, with religious leaders opposing revised legislation to make it permissible (18). The decreased uptake of this secondary prevention measure in both LMIC and HIC results in a higher rate of affected births, requiring lifelong care and considerable socioeconomic impacts.
Five articles in this review highlighted issues related to TOP for foetal abnormality and willingness or reluctance to terminate an affected fetus. Both HCP (21) and patient perspectives (i.e. acceptance of fate and God’s will) were reported (37). The common denominator regarding decisions related to TOP for affected pregnancies by patients/families was identified as religious affiliation (21) . The greater acceptance by HCP may be attributed to their awareness of the significant financial and social burden of caring for an affected child.
2. Emerging Technologies
Reservations towards the use of some specific genetic technologies e.g., PGD, gene therapy and gene editing, was noted amongst HCP. However, religious beliefs are not always a barrier to genetic services, as some doctors from all religious backgrounds are supportive of the newer genetic techniques to assist with reproductive difficulties (18). Beliefs will differ between countries, cultures, religions and individuals. As education of HCP and the public improves around these issues, there may be a greater willingness to consider the benefits of these technologies.
Limitations:
The inclusion criteria of this review included restriction to publications in English only. Many LMIC are multi-linguistic, with numerous languages and dialects within some countries, and relevant studies published in other languages may have been excluded. Additionally, the high-quality English required by many high-ranking, peer reviewed journals may have prevented the publication of some LMIC manuscripts. Publication bias may be an issue, as positive outcomes of studies performed in LMIC may have a higher chance of being published than those with negative findings (Begg, 1989; (63), or negative findings are not written up by the researchers. While this scoping review focused on non-genetic specialist HCP, some articles covered specialist and non-specialist audiences, and these were retained to so as not to omit important information.
The way forward:
Much can still be done for the care and prevention of CD, particularly in LMIC. Suggestions from this review include the incorporation of genetic services by pHCP into primary healthcare, including primary health clinics - with the potential for more accessible, efficient and less expensive services. In-service training and online educational programmes (via short courses and CPD -accredited events) would empower HCP with relevant genetics knowledge, skills and an incentive to remain updated on emerging technologies.
Ultimately, better educated pHCP should improve the identification and management of patients affected by congenital disorders and enable integration into routine clinical practice. Educational strategies for genomics must include basic genetic principles and inheritance, and skills development for clinical management. This will be largely dependent on governmental policies, and the individual willingness and commitment of pHCP to incorporate genetics and genomics into daily practice.
Studies in Africa on genetic knowledge, attitudes, skills and practices is an unresearched/unpublished field. Nevertheless, South Africa appears to be in the unique position on the continent to be able to offer genetic services in the form of medical genetic services and genetic testing. Therefore, HCP have an obligation to improve their genetic knowledge, and know how to initially manage, access, and refer families with genetic conditions to available genetic services.
This review highlights the need for further research on the knowledge, attitudes and practices related to genetics and genomics. Such increased awareness will contribute to an improvement of overall healthcare and improve lives of people and families living with congenital disorders and contribute to no one being left behind (27).