Need for a universal thalassemia screening programme in India? A public health perspective.

Thalassemia is one of the significant public health concerns as the carrier rate and disease numbers are increasing worldwide. The increase in number is because of consanguineous marriage which has a deep-rooted norm among many people globally. Besides various clinical and psychological problems associated with thalassemia, a lifelong treatment aspect makes it much more difficult for a person or family to sustain with thalassemia or thalassemia-affected children. Though the government has come up with a screening programme for thalassemia, given the fact that it is optional, people tend to ignore it. Examples from Pakistan and Iran remind us to have a mandatory prenatal screening programme which is very much cost-effective. With a highly recommended notion, we suggest that it should be universal to have an antenatal screening programme to avert thalassemia-related deaths.

Thalassemia – A Major Public Health Concern

Thalassemia is one of the common hereditary blood disorders manifesting as a wide variety of associated symptoms that usually appear in the first 2 years of life. Untreated thalassemia can result in medical complications which may lead to death. It is also an important public health concern throughout the Mediterranean, Middle East, Southeast Asian Region.[1]

Humans have 23 pairs of chromosomes out of which 22 are autosomes, and 1 pair is sex chromosome. Genes that are responsible for thalassemia are present on chromosome number 11 which is an autosome. Recessive means the disease is manifested only when the genes in both the alleles are affected. The genotype and phenotype are described in Table 1.

Table 1

Genotype and phenotype of thalassemia

Genotype	Phenotype
HH	Normal
Hh	Beta-thalassemia minor (carrier)
	Normal year expectancy
hh	Beta-thalassemia major
	(1–2 years)
	15–20 years on frequent blood transfusion

Let us look at the various combinations in which crossing can occur [Figures 1 and 2].

Figure 1

Inheritance pattern of thalassemia

Figure 2

Inheritance pattern of thalassemia

It is clear from Table 1 and Figures 1 and 2 if both the parents are beta thalassemia minor (Hh), there are 25% chances that they will produce a thalassemia major (hh) child. If the gene is deleted or mutated, there will be impairment or imbalance in the production of globin chains, and that is known as thalassemia. Hemoglobin has four globin chains, two are alpha and two are beta. Depending upon which globin chain is impaired or imbalanced, thalassemia is of two types. If the synthesis of the alpha chain is impaired, it is known as alpha thalassemia, and if the beta chain is involved, it is known as beta thalassemia.

Offspring inherits this disorder from their parents.

So, these kinds of marriages should be prevented to stop the production of thalassemia major children, because the children will die between 1 and 2 years of age and can maximumly survive up to 15–20 years with frequent blood transfusions.

The Outlook of Burden

Thalassemia is one of the most prevalent disorders among inherited conditions – carried in genes and passing from one generation to other, affecting nearly 200 million people globally.[2] Thalassemia poses a serious public health threat globally because of the higher prevalence extending from the Mediterranean region and parts of Africa.[3] National carrier state of thalassemia remains 5% to 7%. Globally, thalassemia affects nearly 4.4/10,000 live births.[4]

In India, every year 10,000 children are being born with thalassemia which approximately accounts for 10% of the total world incidence of thalassemia-affected children[5] and one in eight of thalassemia carriers live in India. The prevalence of thalassemia ranges between 0.6% and 15% across south India.[6]

In India, there are nearly 42 million carriers of the β-thalassemia trait. There are communities in which it is more prevalent like Sindhis, Punjabis, Gujaratis, Bengalis, Mahars, Kolis, Saraswats, Lohanas, and Gaurs. In West Bengal and Northeastern states, specifically Hb E, a variant of hemoglobin, significantly contributes to the disease burden.[7]

Consanguineous Marriage – An Influential Factor

Being a diverse multicultural country, India has various religions and castes. There are around 3000 castes and 25,000 subcastes in India, and most interestingly people in India adhere to their specific caste. Consanguineous marriages are marriages that occur between the individuals who are closely related to one another. Consanguineous marriage remains the choice of an estimated 10.4% of the world population.[6] Currently, one billion of the global population lives in communities with a preference for consanguineous marriage.[8] In people of North Africa, West Asia, and South India, consanguineous marriages are culturally and socially acceptable and constitute 20%–50% of all marriages.[8] Understandably, the expressions of autosomal-recessive disorders are more increased in consanguinity. Consanguinity has got deep roots in the society with one billion people currently living in countries; where consanguineous marriages are customary, and among them, one in every three marriages is between cousins.[8]

Disease Manifestation and Treatment Burden

The effects of thalassemia on physical health can lead to physical deformity, growth retardation, and delayed puberty, and this contributes to poor self-image for the patient.[9] Even, children with chronic physical illnesses like thalassemia are prone to get emotional and behavioral problems.[10] The chronicity and complications of thalassemia not only disturb the quality of life of victims but also it hampers the whole family.[3] Children with thalassemia in the pre-school and latency age groups are usually anxious and excessively dependent on their parents.[1112]

Usually, no visible symptoms are present at birth for children born with thalassemia; it appears in later life.

At present, the complete and only treatment available for thalassemia major is bone marrow transplantation, which only a few patients can afford. For supportive care and management of a child with thalassemia major nearly 100,000–250,000 INR/year is required depending on the age and presence of complications.[1314]

The nature and the particular treatment of this chronic disease impose a heavy psychosocial burden to the patients with thalassemia and their families.[15]

The function of the families mainly depends upon the emotional and physical health as well as their cognitive and social functioning.[16] Experiences and effects of the family members and their reactions towards the children's chronic condition directly affect each other in the family.[17] Its chronic treatment is a permanent reminder to get depressed and makes it impossible to have a normal life.[18]

Health and wellbeing of parents and the family functioning depends mainly on the health of the children. Therefore, the health status of parents and their children strongly depend on each other. A family is the most important source of support for people with chronic disease.[2]

Screening Test

With early prenatal screening and detection, it is possible to diagnose a congenital defect as early as possible during pregnancy. Screening tests and diagnostic tests are the two types of tests. Prenatal screening is recommended for all expectant mothers. Invasive and noninvasive tests are available for screening which can depict the risk for the condition [Figure 3].

Figure 3

(a) Screening procedure. CVS: Chorionic villus sampling; Hb: hemoglobin; IEF: Isoelectric focusing; NESTROF: Naked Eye Single Tube RBC Osmotic Fragility; RBC: Red blood cell; RFLP: Restriction fragment length polymorphism (b) Diagnostic Test

Diagnostic Test

It has been recommended when screening test shows an increased risk of birth defect. When a screening test is positive, and either of the couples shows the presence of a genetic disorder, it is recommended to get it confirmed by a diagnostic test. Diagnostic tests are done in the cells obtained from the fetus by chorionic villus sampling (CVS) or amniocentesis [Figure 3].

Indications of Diagnostic Tests

All the antenatal mothers are advised to go for thalassemia screening through hemoglobin electrophoresis between 10 and 12 weeks of pregnancy. A partner is advised to do screening in case of a positive test result of his spouse, no actions needed in case of a negative test result. A diagnostic test is required further to confirm the presence of thalassemia in the fetus.

Chorionic Villus Sampling

CVS is a clinical test performed during pregnancy to identify abnormalities that are specific to an unborn baby. Genetic defects are tested from the sample of cells taken from the placenta. It is highly recommended in pregnancies where there is a high risk of the baby having an inherited disorder. It is usually done between 10th and 13th week of pregnancy.

Two types of CVS are (1) transabdominal CVS – a procedure that involves a needle which is inserted through the abdomen of pregnant women, observed at all times by ultrasound. It is performed under local anesthesia. (2) Transcervical CVS – a procedure which involves a tube that is inserted through the cervix and observed by ultrasound. Anesthesia is not given in this procedure.[19]

Amniocentesis

Amniocentesis is done in 15–20 weeks of pregnancy or after the 15th week of gestation. Gestational age and fetal viability are tested using ultrasound testing. Evaluation of the fetus is followed by the amniocentesis procedure.

Early screening allows adequate time for work-up and counseling of the couples. Timely identification of thalassemia major helps in preparing for the choice of termination of pregnancy. Antenatal screening is advised to all the pregnant women to plan their pregnancy, about prevention of thalassemia.[19]

Besides the continuous effort of the government in initiating the screening programmes, the gap still exists in the control and prevention of thalassemia. Giving importance to child health, Government of India launched a programme namely Rashtriya Bal Swasthya Karyakram (RBSK). The programme is aiming at early identification and early intervention for children (birth to 18 years) to cover defects at birth, deficiencies, diseases, and development delays including disability.

Child Health Screening and Early Intervention Services under Rashtriya Bal Swasthya Karyakram envisages covering 30 selected health conditions for screening, early detection, and free management in which beta-thalassemia is optional.[20] The reasons may be two fold. Firstly, the epidemiological data is incomplete, and th e precise burden of these disorders is unknown. Secondly, International organizations like WHO and Thalassemia International Federation do not make antenatal screening mandatory.[7]

Mechanisms for Screening at Community and Facility Level [Figure 4]

Community level and facility level are the two levels of child screening under RBSK. Facility-based screening includes newborn screening done at public health facilities –primary health centres, community health centers, and district hospitals conducted by medical officers, staff nurses, and auxiliary nursery midwives.[20]

Recommended algorithm for thalassemia screening at different levels

Community-level screening includes a screening of newborn done by mobile health teams at Anganwadi centers and government schools.

Previous surveys[212223] revealed that there was insufficient knowledge on the detection of carrier status in children and most of the respondents had not heard of the test for detecting thalassemia carrier status. This suggests that lack of awareness due to illiteracy[20] and insufficient flow of resources contributes to the wider spread of the disease; which in turn leads to an increase in burden and its after-effects.[232425]

Recommendations and Conclusion

Fortunately, we have a already screening programme in place for early detection of diseases and intervention for the children (RBSK); now it will not be wise or prudent if thalassemia screening programme remains in an optional category. The necessity of a universal screening programme is strongly recommendable as mentioned, considering its future implications. However, there are limitations in legal abortions in early diagnosis. The potential problem could practically have been solved by screening and then followed by diagnostic tests.[24] We also suggest this recommendation, by comparing the report given from our neighbouring country Pakistan,[21] which demonstrates that prenatal screening is feasible and acceptable throughout the country. One more example which needs a mention here is that of Iran. It has been shown that prenatal diagnosis by CVS and subsequent abortion of the affected fetus is acceptable and affordable to most families who are at risk. Observing experimental results and learning's from Iran on prenatal diagnosis, CVS programme, it is high time to follow the same to reduce the burden of thalassemia in the Indian scenario.[25]

A study of Indian context revealed that by and large, parents have no reservations in sharing information of their affected children with their relatives, most of whom (relatives) accepted the risk of being a carrier and some of them even tested for it. But the communication needs to be improved for all the families to accept the risk of them having a thalassemic child.[26] There is also a need to make the screening more readily available and to motivate high-risk groups through awareness-raising programmes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.