National Sickle Cell Anaemia Elimination Mission. Need for a design re-think !!

The National Sickle Cell Anaemia Elimination Mission  launched by the Union government in July 2023 focuses on “Eliminating sickle cell disease as a public health problem in India before 2047 “ as well as addressing the significant health challenges posed by sickle cell disease. ¹

Sickle cell disease (SCD) is an inherited blood disorder, that results in modest anaemia, often referred to as sickle cell anaemia. This condition alters the shape of red blood cells, causing them to become rigid and sticky, potentially leading to either slowing or blocking of blood flow that affects organs and causes acute painful episodes. The disease is associated with a significant risk of early childhood mortality, primarily due to infections like pneumonia. Survivors may face chronic organ damage, resulting in a notable reduction in life expectancy.

SCD is a chronic single-gene disorder requiring the inheritance of two SCD gene copies, one from each parent, for manifestation. Individuals with only one copy, known as carriers or having the sickle cell trait, exhibit no disease symptoms. The carrier frequency of the SCD gene varies widely, ranging from 1% to 35%. By the Global Burden of disease estimates , an estimated 82,500 births with SCD occur annually in India ², and the prevalence is estimated at   1.28 million cases, making it a significant public health concern. Additionally, β-Thalassemia, another inherited blood disorder, is also prevalent in India, with carriers averaging a frequency of 3-4%.

Implemented in 17 high-focus states across the country, this Sickle Cell Anaemia Program (SCAP) aims to improve the care and prospects of all sickle cell disease patients while reducing the prevalence of the disease. The 17 states are- Gujarat, Maharashtra, Rajasthan, Madhya Pradesh, Jharkhand, Chhattisgarh, West Bengal, Odisha, Tamil Nadu, Telangana, Andhra Pradesh, Karnataka, Assam, Uttar Pradesh, Kerala, Bihar, and Uttarakhand.

The program is to be executed in mission mode as the National Sickle Cell Anaemia Elimination Mission. The Mission goal is to eliminate sickle cell genetic transmission by the year 2047, showing a long-term commitment to eradicating the disease. The main strategies outlined the Operational Guidelines issued by the Ministry of Health and Family Welfare³ are:

1. Primary prevention strategies: involve creating awareness, providing pre-marital and pre-conceptional counselling, genetic counselling and testing interventions in high prevalence districts, and health promotion activities with widespread community involvement.
2. Secondary prevention and Screening: approximately 7.0 crore people under 40 years of age in the next 3 years to identify those with sickle cell carrier state and those with disease.
3. Sickle cell genetic status cards: Issued to all those screened. They would be encouraged to match this card before deciding on marriage to reduce incidence in next generation.
4. Holistic management and continuum of care: for those affected through primary to tertiary care support, advanced diagnostics, and treatment, Ayushman Bharat enrolment giving them free access to services, The integration with AYUSH, patient support, and rehabilitation.
5. Prioritize tribal communities in India: the mission prioritizes its intervention in the high prevalence and tribal states.

The official press release at the mission launch highlighted the Prime Minister distributing Sickle Cell Genetic Status Card to the beneficiaries and that he “kickstarted the programme with distribution of about 3.57 crore Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB-PMJAY) cards”⁴. In the same meeting, the health minister also urged that people should match Sickle Cell Genetic Status Cards before marriage, to ensure that the disease is not transferred to the next generation:

As per the Mission dashboard as of February 20^th, 2024, 1.98 crores have been screened, and of these 6.10 lakhs have sickle cell trait (meaning a single copy of the gene- also known as heterozygote) and 1.09 lakh have been found to have the disease (two copies of the gene – also known as homozygote) and in another 2.84 lakhs the disease is suspected after the first test, but the confirmatory second test is awaited.

While the renewed focus on a neglected illness like SCD is welcome, there are major unsettled ethical and effectiveness concerns with the current strategy-design.

• The idea that we can eliminate a genetic disease.

Eliminating selected diseases has become a goal since we eliminated smallpox forty years ago.  We have targets for eliminating poliomyelitis, tuberculosis, malaria, kala azar, filariasis in our calendars. But all these illnesses are infectious diseases and are amenable to intervention at the causative agent and the transmitting environment besides the host for us to maintain hope in disease elimination. SCD is an autosomal recessive genetic disease whose elimination is only possible by preventing births of people with this disease. Even if there were no new cases each year, since the heterozygote state will always continue, the gene remains in the population. Even the elimination of a marriage between a man and a woman both having sickle cell trait is a near impossible goal and is fraught with many ethical, operational, and social issues. Mitigating the effects of this disease and ensuring the highest quality life outcomes for people who suffer is a more reasonable goal, which is what all other countries in the world aspire towards.

• The conflation of sickle cell disease with Adivasis.

Surely, the Adivasis have it in higher proportion than what it would be if the disease was uniformly distributed. The sickle gene emerged and underwent selection in humans around 30,000 years ago, providing protection against severe falciparum malaria-related deaths in a heterozygote state. As falciparum malaria is most prevalent in forest and forest fringe ecosystems, regions like the central Indian belt from Gujarat to Bengal and the northeastern states have a higher prevalence of the sickle gene, with a significant proportion of adivasis residing in these areas. While it’s accurate to state that nearly half of individuals with sickle cell disease may be adivasis, it’s crucial to avoid categorizing sickle cell disease solely as an Adivasi illness. This characterization not only misleads but also poses a risk of fostering stigma and discrimination, as the disease affects both adivasis and non-adivasis.

• Our diagnostic plan is not in place, and the hope that is invested in the Point of Care Diagnostic (POC) may be premature!!

The diagnosis of sickle cell disease traditionally has been a two-stage process- a screening test done at the point of care, which is cheap and easy to do, and then a confirmatory test like a hemoglobin electrophoresis, which would be done in a referral laboratory. Inefficient logistics management in our public health systems, make stock outs of the cheap reagents for the solubility screening test a common occurrence in many states. The larger problem is the near absence of any confirmatory testing facility for the great majority of those screened positive. In the last few years, we have had the availability of a point of care (POC) test, as a rapid diagnostic kit, that combines the two stages and thus give the treating team a confirmed diagnosis. These POC tests are now increasingly being used in the public health system- both as a screening+ confirmatory test, and as a confirmatory test once the solubility screening test is positive. There is much hope that this will be a game changer in the diagnosis and care of sickle cell disease and if so, that would be welcome. Nevertheless, there is insufficient field experience with these, and numerous field reports[1] raise concerns about the reliability of test results, with published data still unavailable.

4. An unaddressed need for demystifying treatment of SCD and decentralizing treatment initiation and management with hydroxyurea to  primary care providers

We have had a cheap drug like hydroxyurea for the last 20 years that is recommended for almost everyone with sickle cell disease for a lifetime. This controls the disease in over 90% of patients. But its widespread use is still to happen, with many physician administrators and physicians showing reluctance in its use. Regular uninterrupted supplies of this drug and ensuring that the patient can access this drug at the level of primary healthcare provider would be a game changer. Besides hydroxyurea, medicines for pain crisis, and antibiotics to treat infections and pneumococcal vaccines which all those with the disease must take are also priorities that are essential for good comprehensive care and preventing deaths. This should be a top priority for the entire health system.

Sickle cell disease is now included as a disability about which there is little to no knowledge among health professionals and public. More importantly even the benefits of people with disabilities are not readily available, for example reservation for jobs and for education. The emphasis on enrolment in PM-JAY seems to imply that this is largely a tertiary care intervention, when on the contrary it is a condition which is best managed at the primary care level, except  during a sudden exacerbations. And such exacerbations can be almost completely prevented.

5. The focus on blood transfusion has to be brought down, even as a measure of the effectiveness of our management plans.

Sickle cell disease patients had traditionally been given a tablet of folic acid and frequent blood transfusions, especially when they had painful crisis. If the disease is managed correctly with hydroxyurea, and analgesics and antibiotics when needed, the proportion of sickle cell disease who require blood transfusions can be brought down to less than 10%. At any rate, blood is a precious therapeutic agent, which should only be used when essential. We can be confident that once we put in place a rational management strategy for all sickle cell disease patients, unwanted and inappropriate blood transfusions would stop.

6. Importance of a Community Based Approach : for a chronic disease demanding daily treatment and for decades,.

The duration of most chronic diseases like diabetes, epilepsy, hypertension, severe mental disorders, and sickle cell disease is often life long, and thus treatment and regular follow up is needed for many years and decades. To maintain compliance and continuity of therapy for these illnesses is frequently a challenge. For example, it is known that compliance with treatment of hypertension and its adequate control is less than 20% in institution-initiated care. Community based approach to care for chronic diseases is mandatory if we wish to maintain a reasonable continuity of care. This means facilitating formation of peer support groups of patients with this disease, availability of drugs and follow up care close to people’s homes and larger role for community-based health workers. These features are   almost completely missing in the present design of the sickle cell disease program.

The Odisha government has taken the initiative of providing transport support to the tune of INR 500 per month for patients with SCD, which is worth emulating by other states.

[1] Personal communication from several sites in Chhattisgarh with  author, YJ.