Symposium : Genetics for Pediatricians-I
Medical Genetics in Primary Health Care Arnold L Christianson
Dfpartment of Human Genetics and Developmental Biology, Faculty of Medicine, University of Pretaria, Prctoria, South Africa Medical genetics has been at the forefront of developments in medicine for the last 50 years. This progress has mainly benefited industrialized countries. Due to continuing improvements in the socio-economic and health indices in developing nations more than half of them have now reached a stage where it has become relevant for them to initiate and develop medical genetic services. The WHO foresaw this eventuality in 1985 and further recognised the need to develop community based medical genetic services that are relevant to and can be incorporated into primary health care. The need for primary health care based medical genetic services has subsequently also been accepted in industrialized nations. This paper summarises those primary health care based interventions that can be undertaken to ensure the control of genetic disorders and birth defects. [Indian a Pediatr 2000; 67(11) : 831-835] Koywords : Primary health care, Medical genetics.
Medical genetics has been in the forefront of developments in medicine for the latter half of the last century culminating with the recent announcement of the mapping of the human genome. The benefits of this progress have been significant, particularly in industrialised countries. By comparison limited impact has ensued in developing nations where 80 percent of the world's population resides and 90 percent of i~s birth occurs1. Because infectious diseases and malnutrition are erroneously considered to still cause an unacceptably high proportion of infant and childhood mortality and morbidity in developing nations, a persisting concept exists that medical genetics is a field of endeavour appropriate only for developed countries. The reality is markedly different as many of the developing nations are undergoing a significant epidemiological transition. Improvement in the socio-economic and health indices in at least 75 (53%) of the world's 147 developing nations, in which some 2.8 billion (60.5%) people live, have resulted in their evolution to a situation comparable to that experienced in most industrialised nations in the 1950s and beyond 2. In these countries the previously obscured public health significance of genetic disorders and birth defects is becoming apparent resulting in the necessity for the initiation and development of medical genetic servicesTM.Significant barriers to the provision of medical genetic service also exist in industrialised Rep~mt requests : Dr. Arnold L. Christianson, Department of Human Genetic & Development Biology, Faculty of Medicine, University of Pretoria, Post Box-2043, Pretoria, South Africa. E-mail :
[email protected]. Indian Journal of Pediatrics, 2000; 67 (11) : 831
nationsl,L Thus a worldwide need exists to develop approaches for the equitable provision of medical genetic services. The purpose of medical genetic services has been defined to help the genetically disadvantaged to live and reproduce as normally as possible 2. This requires the implementationof a control program for genetic disorders and birth defects which consists of an integrated strategy combining best possible patient care, with prevention of genetic disorders and birth defects by community education, population screening, genetic counselling and the availability of prenatal diagnosis. Therein, treatment and prevention are combined in the development of medical genetic programmes. At the population of community level this necessitates the integration into the existing primary health care (PHC) system of a combination of public health and medical genetic measures. This indudes the requisite education and training of PHC practitioners. These PHC approaches need to be developed and initiated within the limits of local circumstances and customs, and available manpower and material resources. The system developed also requires to be networked with available secondary and tertiary medical services, particularly in reproductive health, obstetrics, pediatrics, and other social services1'4'~. In 1985 the WHO recognised the need to develop community based medical genetic services which were relevant to and could be incorporated into PHC 3. This necessity has become increasingly more apparent since then even in industrialised nations, culminating in two recent WHO documents on this issue and the first International Conference on Community Genetics in June 20001,4-1~
Arnold L Christianson
Patient care in primary health care
Worldwide, barriers to patient care include economic constraints, lack of appropriately educated and trained manpower, isolation of medical genetic services in tertiary care services, ethnicity, language, religion, culture and geographic isolation1,~6.To overcome these barriers, it is now recognised that the services necessary to do so require to be undertaken at community level by primary care practitioners. Care of patients with genetic disorders and birth defects is challenging. The outcomes are frequently limited, especially in developing countries, where prognosis for many patients is mostly infant or early childhood death. Despite this all patients affected with a genetic disorder or birth defect, and their families, are entitled to expect the 'best possible patient care" available in the prevailing circumstances1,4. Patient care in this context includes diagnosis, therapeutic intervention, if possible, and available genetic counselling and psychosocial support. Primary healthcare practitioners need to be educated and trained to enable them to render the 'best possible patient care" within the framework and capacity of their country's health, education and social welfare systems. "Best possible patient care' in the PHC setting requires delineation. It comprises early and accurate diagnosis of commonly prevalent genetic disorders and birth defects. This allows for triage and appropriate further management, which to the greatest extent possible must be undertaken at PHC level. This should include basic genetic counselling, psychosocial support and treatment such as antibiotics, cardiac failure treatment, anti-malarial prophylaxis and neurodevelopmental therapy. Psychosocial support includes referral to and assistance from allied services including education and social welfare. Where diagnosis and treatment are not available, and in situations in which they will significantly improve prognosis, patients should be referred to the appropriate facility for further care (e.g. for diagnosis and management of complex conditions, surgery, visual and auditory assessment and management). In turn many of these patients will be referred back to their PHC facilities for on-going management. It has to be recognised that for numerous conditions 'best possible patient care' at PHC level may consist of terminal/palliative care, and primary care practitioners need to be capable of assuming this responsibility1,n. It is the author's opinion that in the development of PHC based genetic services "best possible patient care" is an absolute and prevention of genetic disorders and birth defects is the ideaP ~ Once diagnosis and treatment options for genetic disorders and birth defects become available, patients survive longer, population prevalence of these conditions increase, resulting in the concomitant rise of the financial burden to the healthcare system for patient 832
care. Simultaneous implementation of strategies for the effective prevention of genetic disorders and birth defects thus becomes a cost-saving and cost-effective prerequisite for the continued further development of medical genetic services at all levels4,5. Public health approaches for prevention of genetic disorders and birth defects in primary health care: At the community or population level, prevention of genetic disorders and birth defects initially requires the implemen~tion of a series of basic public health measures in PHC 1,~swhich include : Familyplanning.The availability and appropriate use of family planning plays an important role in the prevention of genetic disorders and birth defects. In situations in which infant and childhood mortality is reducing and family planning is available, parents tend to stop reproducing once they have their desired number of children. Thus the crude birth rate declines resulting in a decrease in affected children. In addition women of advanced maternal age (>35 years of age), who are at significantly increased risk of delivering an infant with a chromosomal disorder, reproduce less with a concomitant reduction in the birth of infants with chromosomal abnormalities, particularly Down syndrome. Couples with a known increased genetic risk, determined by family history or genetic screening, can limit further reproduction with family planning, thus avoiding the risk of having further affected children. Maternal nutrition: There is growing evidence of the need to optimise maternal nutrition during a woman's reproductive period, especially during pregnancy, to prevent birth defects. This should include prevention and correction of maternal anaemia and malnutrition. Evidence is emerging of the predisposing influence of maternal health and nutrition on common multifactorial diseases. The efficacy of dietary supplementation on the occurrence and re-occurrence of neural tube defects and possibly other birth defects is now well documented. Maternal iodine deficiency; which often occurs in central arid and mountainous regions, can lead to impaired fetal brain development and should be avoided. In addition to ensuring that women obtain an appropriate diet with respect to proteins, calories, vitamins and n~'cronutrients, it is also necessary to make sure that they are aware of the dangers of substances to the fetus that may be imbibed or ingested, including alcohol, smoking and recreational drugs. Maternal health : Maternal ill health during pregnancy predisposes the fetus to increased risk of birth defects. This should thus be detected and avoided whenever possible. Women with insulin-dependent diabetes meUitus have a two to three times greater risk of a seriously malformed infant compared to the general popuIndian Joumal of Pediatrics, 2000; 67 (11)
Medical Genetics in Primary Health Care
lafiorL This risk can be reduced by careful diabetic control prior to conception and during pregnancy. Some epileptic medications including sodium valproate, phenytoin, carbamazipine are teratogenic. It is usually not possible or advisable to discontinue anti-epileptic medication during pregnancy. If possible, prior to conception, seizure control with a non-teratogenic medication should be obtained. Further, as a general principal, epileptic monotheraphy with the lowest dosage possible should be used whenever possible. Maternal infection : Worldwide, these represent the greatest risk to the fetus, particularly human immunodeficiency virus (HIV/AIDS) and syphilis. Early diagnosis of these infections in order to initiate treatment to reduce the risk of vertical transmission and teratogenesis to the fetus is important. In the case of syphilis, treatment of the mother with penicillin is safe, efficacious and cost effective. A number of strategies including the use of anti-retroviral agents, elective cesarean section and disinfection of the vagina during labour and delivery have been used to reduce the risk of fetal infection with HIV. Impediments to the use of anti-retroviral drugs include cost and availability in many developing nations, and it is not practical in such countries with a high HIV prevalence to encourage the use of elective cesarian section. Rubella infection is still a potential cause of birth defects especially in developing countries where immunisation of schoolgirls is not practised. Each country needs to assess its own need to initiate such a programme. Alternately, screening and immunisation of non-immune women of reproductive age prior to marriage can be considered. Medical genetic approaches for the prevention of genetic disorders and birth defects in primary health care The public health approaches described above can be integrated into a functioning PHC system. Once achieved this will assist in the reduction of the baseline birth prevalence of serious genetic disorders and birth defects. To achieve a fttrther decrease in the birth prevalence of these conditions requires the implementation of population screening programmes 5. By their nature population screening programmes are based in PHC but require to be well integrated with medical genetic, laboratory, prenatal diagnostic and termination of pregancy services in secondary and tertiary facilities. Population screening seeks to identify people at risk of having a child with a genetic disorder or birth defect, in order that they may be forewarned and offered appropriate reproductive choices. The recognised prerequisites for a population screening programme are that the target condition is common, clinically well delineated, serious and the screening will produce a definitive diagnosis. There must also be available, effective management options for treatment and / or Indian Journal of Pediatrics, 2000; 67 (11)
prevention and the programme should be cost efficient. Different options for population screening programmes exist, and each country would need to decide which programmes to initiate according to their needs and circumstances 4,s. The choices include : Carrier screening : In situations where an inherited disorder is very common it may be feasible to systematically screen the entire population for carriers. Conditions that could be considered for such a programme in different parts of the world include the haemoglobin disorders (thalassaemia, sickle cell anaemia, glucose-6-phosphate dehydrogenase deficiency) and cystic fibrosis. The well documented success of such programmes for thalassaemia in Sardinia and Cyprus bears testimony to the efficacy of such programmes. Antenatal ultrasound screening: This can be a major tool for detecting serious congenital malformations but is expensive and requires a sophisticated infrastructure to be implemented. It is also not universally acknowledged as an acceptable method for population screening. Antenatal screening for chromosomal disorders : This can be undertaken in two ways. Mid-trimester maternal screening is available in many industrialised countries. It is reliant on an accurate estimation of gestational age, and thus is not feasible in situations where antenatal ultrasound dating is not available. The increasing risk of chromosomal trisomy, particularly Down syndrome, with advancing maternal age (AMA) allows the possibility of offering to older women, prenatal diagnosis by genetic amniocentesis and karyotyping of fetal fibroblasts. An important role for the primary care worker in this situation is to detect pregnant women of AMA and refer them in time for genetic counselling and possible amniocentesis. Preventing severe neonatal jaundice: Two genetic conditions, Rhesus incompatibility between mother and fetus, and neonatal glucose-6 phosphate dehydrogenase deficiency (G-6-PD) can cause neonatal jaundice, severe enough to abuse death and disability from kernicterus. Screening for Rhesus negativity and the administration of anti-D immunoglobulin after birth and abortion to Rhesus negative women has significantly reduced mortality and morbidity from Rhesus haemolytic disease of the newborn. Neonatal screening for G-6-PD in areas where this is a significant problem is recommended as well as advice to parents on environmental factors that can aggravate the problem. These include local herbal remedies and clothes stored with naphthalene mothballs. Fava beans can cause haemolyfic crises in children and adults and should be avoided. Family history : Inherited disorders occur in families. By their nature a person affected with one can pass the condition and / or the abnormal gene on to their child in the subsequent generation. In addition, the disorder or the 833
Arnold L Christianson
abnormal gene may be present in individuals in the same or other generations. Therefore, documenting a proband's family history can be a powerful tool, when combined with appropriate genetic testing, for detecting family members who are at increased risk of having the same disorder or being carriers of the abnormal gene, depending on its pattem of inheritance. A family pedigree is also useful in detecting parental consanguinity, which places the couple at increased genetic risk for a child with an autosomal recessive condition. In both situations obtaining a farrfily history facilitates subsequent genetic counselling. Taking and interpreting a family history is an ability that is well within the capabilities of primary care practitioners and they should be trained to use this invaluable tool. Newborn screening: Usually this is considered to be biochemical neonatal screening u s i n g filter p a p e r (Guthrie) cards to test for conditions that include metabolic and haemoglobin disorders (e.g. congenital hypothyroidism, phenylketonuria, G-6-PD, sickle cell anaemia). Each country needs to decide on its priorities in this regard. However, a trained primary care practitioner should examine all newborns for genetic disorders and birth defects. This is not the case in some developing nations, and clinical newborn examination thus constitutes the most basic form of newborn population screening n .
Thus its principles and practice should be i n d u d e d in the core curriculum of all practitioners including those in PHC. Thereafter, primary care practitioners should be educated, trained and supported to manage common problems to the greatest extent possible at the primary health care level. Each country will require to develop its own curricula and education and training programmes to accomplish this within the context of its health, education and social welfare systems and the social, religious and legal milieu. New technologies are becoming available to assist with this process including telematic education and information technology. An example of the latter is the ApoGI programme that makes available on CD and the internet, genetic information on haemoglobin disorders appropriate for the use of primary care practitioners 12. Communityeducation. It is essential for the success of any control programme for the public to be educated with appropriate knowledge in order that they can understand and accept the tenets of the programme and be able to utilise it appropriately and to their advantage. Such education should be considered as health promotion and be undertaken by governmental and non-governmental organisations including patient / parent support groups ~,5.
Genetic Counselling
Historically medical genetic services have been rendered from tertiary, mainly academic, centres. The need to diversify these to PHC has now been recognised and accepted. In developing countries it is recommended that it would be beneficial to ensure the involvement of PHC from an early stage. The basis for this involvement, summarised above, has been detailed in three recent WHO documents, to which the reader is recommended for further detail and amplification l'*'s. However, it is important to note, that before any prog r a m m e to introduce medical genetics into primary health care is embarked upon, this requires full governmental political will, commitment and financial support to underpin the process 1,~".
Integral to the delivery of medical genetic services, for both treatment and prevention, at all levels of care induding PHC, is genetic counselling. This seeks in a nondirective manner to educate patients and their family about the disorder in question, the genetic risk implidt to family members, and the options available for management and prevention. Its objective is to empower those counselled to be able to make their own informed decisions regarding their situation according to their beliefs, customs and circumstances. Their caregivers must then support these decisions1-~.Primary care practitioners are in many ways ideally suited and placed to give genetic counselling. They reside in the area of their patients, speak their language, understand their customs and beliefs and are usually well respected by the community n. For them to be able to undertake this takes, they require to be appropriately educated and trained to give genetic counselling, at least for those conditions that are common in their region. Education
Primary care practitioners : Increasingly medical genetics is becoming central to the practice of medicine. 834
CONCLUSION
Acknowledgement
The author would like to recognise Professor B. Modell, Dept. of Primary Care and Population Sciences, University College London Medical School, and Professor V.B. Penchaszadeh, Beth Israel Medical Centre, New York, with w h o m he has had the privilege and pleasure of working with over the last few years, and who were instrumental in developing many of the concepts in this article. Indian Journal of Pediatrics, 2000; 67 (11)
Medical Genetics in Primary Health Care REFERENCES
1. WHO Services for the prevention and management of genetic disorders and birth defects in developing countries. Report of a WHO/WAOPBD Meeting. The Hague, January 1999. Document WHO / HGN / GL / WAOPBD / 99.1.WHO, Geneva, 2000. 2. UNICEF The state of the world's children 1999. Education 1999, UNICEF, New York. 3. WHO. C o m m u n i t y approaches to the control of hereditary diseases. Report of a WHO Advisory Group o n Hereditary Diseases. Geneva, October 1985. Unpublished WHO document HMG / AG / 85.10. Hereditary Diseases Programme. WHO, Geneva, 2000. 4. Alwan AA, Model B. Community control of genetic and congenital disorders. Technical Publication Series, No 24. Alexandria, WHO Regional Office for the Eastern Mediterranean, 1997. 5. WHO. Primary health care approaches for prevention and management of congenital disorders and disability.
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6. 7. 8. 9. 10. 11.
12.
Report of a WHO Meeting. Cairo, December 1999. Document WHO / HGN / WG / 00.1. Human Genetic Programme. WHO, Geneva. In press. Paul N, Kavanagh L. (eds) Genetic services for underserved populations. Birth Defects: Original Artide Series 1990; 26 (2). Qureshi N, Raeburn JA. Clinical genetics meets primary care. BMJ 1993; 307 : 816-817. Penchaszadeh VB. Genetics and public health. BulIPAHO 1994; 28(1) : 62-72. Christianson AL, Gericke GS, Venter PA, Du Toit JL. Genetics, primary health care and the third world. (Opinion). S. Afr Med ] 1995; 85(1) : 6-7. Gaudet D. From DNA to the Community. Community Genet 1999; 2 : 139-140. Christianson AL, Venter PA, Modiba JI-I, Nelson MM. The development of a primary health care clinical genetic service in rural South Africa-the Northern Province experience 1990-1996. Community Genetics. In Press. www. chime.ucl.ac.uk/ApoGI/.
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