The burden of thalassemia disorder: Past and present: The feedback of patients experience in the COVID-19 pandemic crisis

Abstract

Thalassemia is a genetic blood condition and one of the emerging global public health concerns in the world, with an estimated prevalence of 300,000,000. The genes controlling hemoglobin production are affected, leading to an anemia of variable severity. Carriers of this hereditary anemia are found globally, but a high frequency is observed around the Mediterranean basin, in the Middle East, in the Indian subcontinent, and in Southeast Asia, so called the thalassemia belt. This article aims to review the history and factors of spreading of thalassemia, to identify the burden of the disease on individuals, population, and public health, and the issues that thalassemia patients have experienced during the pandemic of COVID-19. Online literature and previous studies on the disease are used to prepare this article. We identified various factors that have contributed to the spread of thalassemia in the last decades and affected the health condition of individuals and population. The recent worldwide pandemic of COVID-19 worsened the situation and made it more complicated for most patients, especially in the emerging countries.

Introduction

Thalassemia is a genetic blood condition and one of the most common rare diseases in the world, with more than 60,000 new births every year.[1] The genes controlling hemoglobin production are affected leading to an anemia of variable severity; minor, intermedia, and major. Carriers of this hereditary anemia are found globally, but a high frequency is observed around the Mediterranean basin, in the Middle East, in the Indian subcontinent, and in Southeast Asia,[2] so called the thalassemia belt.

Alpha- and beta-thalassemias are the main types of thalassemia where the hemoglobin molecule is, respectively, very little or not produced.[3] Patients with beta-thalassemia major, the most severe form, need chronic blood transfusion, and iron chelation therapy.

The thalassemia belt is a wide area that includes 19 countries from the Middle East and North Africa (MENA: mostly Arab), 12 countries of South Europe, 6 countries of the Indian subcontinent, and 9 countries of South-east Asia. The area has a population of more than 2 billion people and is known to have a high prevalence of thalassemia where the frequency of carrier varies between 1% and 11%.[4] The diversity of thalassemia in this area is caused by the admixture of genes between different ethnic groups coming from the Gulf, Indian subcontinent, and MENA region. This has been intensified by the influx of many other nationalities and gene migration from Africa, Eastern and Central Asia, in recent decades.

To fight the expanding disease, public awareness and programs have been implemented by governments and health organizations in many countries over the last decades. These efforts seem to have encouraging results to reduce the prevalence of the disease. Programs, comprising health education, health protection, and health prevention, aim to informing them about their personal health and the health of their progeny[5] so they can be aware of the risks and dangers.

The thalassemia belt covers MENA, South European, Indian subcontinent, and Southeast Asian countries.

Materials and Methods

A systematic review was conducted to identify different sources of information on blood disorders and thalassemia in the MENA, Mediterranean, and Asian countries. The Internet site of the Thalassemia International Federation was consulted for the latest updates on the disease. The second edition of “Prevention of Thalassemias and Other Hemoglobin Disorders” book, volume 1: principles, distributed for the 2^nd MEGMA conference on thalassemia and other hemoglobinopathies, served as a scientific literature. A map of the distribution of thalassemia is drawn, representing the most affected regions in the world (the thalassemia belt) to better understand of the spread of the disease, and finally, articles and interviews about patients experience in the COVID-19 pandemic were reported in this article.

Thalassemia: A Multifactorial Disease

Different factors have contributed to the distribution of thalassemia in areas ranging from North Africa to Southeast Asia, including the Mediterranean basin and the Middle East region [Figure 1]. The most reported factors are:

Figure 1.

The thalassemia belt covers MENA, South European, Indian subcontinent, and Southeast Asia countries

Consanguinity

Marriage within families, known as consanguinity, has been common in those regions for several centuries. The practice is common for Muslims and other cultures; therefore, thalassemia is found in high prevalence in Arab countries, in the Mediterranean basin, in Turkey, and in South Asia, where at least one in four marriages involves related family members. Consanguinity marriages are motivated by religious, sociocultural, and economic reasons. They are mostly seen in poor and rural communities, where the population has low levels of maternal education, characterized by early marriage age, short birth intervals, and longer reproductive spans.[6,7]

Migration

In the last few decades, the active migration of healthy carriers of thalassemia has contributed to the spread of blood diseases in the host countries. Their descendants, affected patients, are spreading the disease in a population where it was previously rare or unknown.

Lack of optimum care

The management of thalassemia is multidisciplinary and requires a lot of resources and efforts. Many host countries are often unprepared for new health problems such as thalassemia. These countries, which are generally poor, have other health priorities such as communicable diseases of high mortality of infants and young children. The health-care system in these countries cannot adequately support chronic and rare diseases and provide adequate drug supply due to the difficult financial situation and lack of patient organizations.

Nonetheless, the evolution of health care could also be considered a global factor in the spread of Thalassemia. since The progress of social and health policies, along with the enhancement of the management of blood diseases, and of malnutritional and infectious diseases, have significantly contributed to the reduction of excess mortality and to a better life expectancy,[8,9] saving patients' lives and increasing the number of thalassemia patients at the same time. Thus, the condition has changed from being fatal to chronic.

Challenges Faced by Thalassemia Patients

The thalassemia heavy therapy has a substantial impact on patients and their families, and the burden for the society and the health-care system is significant. The consequences on schooling are often harmful for young patients, since they have to skip classes to receive the treatment, blood transfusion, and other analyses, their school performance is generally poor and sometimes they leave school early to entirely focus on the disease. Furthermore, finding a job is a big challenge for patients because of their poor health conditions and for the disease treatment. Thalassemia patients, especially with severe conditions face difficulties in planning families, which psychologically affects them. Financial issues represent another challenge for the patient and the family because the treatment is costly and requires a significant budget to cover the blood transfusion, iron chelation therapy, medical consultancy fees, laboratory services, and treatment of adverse effects. The absence of health-care funders and patient support organizations adds another burden to the society and health-care system. Therefore, patients often experience social isolation, social negligence, and sometimes discrimination.[10]

The misapprehension that carriers of thalassemia will manifest the disease is another misunderstanding of the disease.

The Importance of Health Education, Awareness, and Prevention

Many countries in the thalassemia belt, in particular countries with limited or low income, choose to educate parents on thalassemia and risks for future children as the best preventive approach and cheaper method to reduce the occurrence of the disease. This prevention consists of:[11]

• Finding the carriers of thalassemia through a survey and informing them about the risks and dangers

• Before marriage screening allows couples to discuss the health of their family. This is also helpful to plan pregnancy

• Prenatal diagnosis of parents who had affected children.

The education of at-risk couples raised the awareness and led to fewer births compared to prenatal diagnosis. Nevertheless, in many remote places, the cultural heritage remains a problem for educating, preventing, and treating the disease. In fact, some religious convictions are shown to be a barrier, for example, Muslim and some conservative societies in South Asia, for example, India, Sri Lanka, and Nepal, have been reported to refuse prenatal diagnosis.[7] The financial and logistic issues are other barriers to conducting surveys, providing prenatal and antenatal screening programs, and counseling services in these distant places.[12]

Thalassemia and the COVID-19 Pandemic

COVID-19 is caused by the SARS-CoV-2 virus and is primarily transmitted through respiratory droplets. Blood or blood transfusion is not demonstrated to be a direct cause to spread the virus and blood diseases are not related to respiratory conditions in general. However, depending on the severity level of the infection, the virus could be dangerous to thalassemia patients because it may involve other organs such as the lungs, liver, and heart. To date, there are very few clinical records of thalassemia patients infected with the virus[13] for instance a case reported in Pakistan of a patient with thalassemia major reinfected with the COVID-19.

The COVID-19 pandemic surprised the most organized institutions, all services were disorganized in the beginning, and this was a very difficult period for thalassemia patients, which is a lifelong condition. It increased the risks and the burden of the disease. Several reports have stressed an acute shortage of blood in most countries. The pandemic and lockdowns have anticipated the closure of many blood donation camps and several of them were converted to COVID-19 centers to help fight the pandemic. Thalassemia patients coming to centers for regular blood transfusion faced a real risk of contracting the virus by contact with other patients or attendants who might be asymptomatic carriers of the virus. Furthermore, the fear of contracting coronavirus has encouraged thalassemia patients and blood donors to avoid hospitals and health-care centers, despite all the necessary precautions and safety measures put in place. Due to some precautionary and restrictive measures such as physical distancing, COVID-19 testing, temperature checking, and sanitization, the visit time in a hospital for blood transfusion or blood donation was increased adding more discomfort to patients and people accompanying them.

In India (India is the thalassemia capital of the world with 3000 ethnic groups and nearly 40 million carriers [Sanjay Ghandi Postgraduate Institute of Medical Sciences]. The average prevalence of beta-thalassemia is 3%–4% and it varies from state to another), for instance, local media reported that many organizations such as “the National Thalassemia Welfare Society” and other local NGOs have asked patients to get a blood transfusion in other hospitals or to visit smaller centers, generally less frequented but at the same time less well-equipped and with fewer services. While in the United Arab Emirates, doctors confirmed that the three thalassemia centers in the country continued their normal operations during the pandemic, normal blood supply, and treatments with respect to all precautionary measures.

In Tunisia, due to the lockdown, many patients from rural regions reported difficulties to travel to their blood centers for transfusion confronting them with the risks and dangers of both thalassemia and pandemic.

Today, according to the World Healthcare Organization, most countries have achieved significant success in fighting COVID-19[14] due to vaccination and preventive measures, so the priority now is to work to restore all that the pandemic has damaged, including for thalassemia patients.

Discussion

Several studies have been conducted on thalassemia, however, the data in some countries such as the Middle East and the Indian subcontinent still very sparse or introductory, especially in the absence of a national registrar.

Knowledge regarding thalassemia is not sufficient, in particular in countries with educationally and socioeconomically disadvantaged population, namely Yemen, India, Pakistan, Nepal, and Bangladesh. It is important to dispel this misconception so that carriers of thalassemia are not stigmatized; the knowledge deficit and misunderstanding of the disease result in unnecessary anxiety among the public and have negative emotional effects on both carriers and thalassemia patients. Therefore, educational efforts are required to raise awareness, especially among the minority and isolated groups, and to improve the perception gaps.

Premarital or preconception screening remains options but are not yet introduced systematically in most parts of the MENA and South Asia regions. However, these methods, which are strongly recommended, are useful to reduce the incidence of thalassemia. Prenatal screening is the predominant practice, allowing diagnosis at an early stage and enabling prevention of new thalassemia births. Genetic counseling plays an important role in the implementation of thalassemia screening programs by helping individuals and families understand better their disease and dispel misunderstandings.

During COVID-19, thalassemia patients faced unprecedented challenges because of the COVID-19 pandemic. The highest risk was the lack of the availability of donors and blood and other conditions such as transportation, centers, and complementary therapies rather than the virus. It was mandatory to protect these patients from contracting the virus and to bring closer the necessary services and therapies.

In this article, the authors stress the importance of understanding the history of and factors affecting the spread of thalassemia in the MENA, Indian subcontinent, and Southeast Asia regions to search for the best solution to stop disease burden in the future. The topics discussed in the article are helpful for basic teaching but also to use for educational material by medical societies and associations involved in blood hemoglobin diseases. The article is also a reminder to all stakeholders to keep supporting thalassemia centers and thalassemia patients in the difficult and challenging situation posed by the post-COVID-19 pandemic.

It is evident that all areas in thalassemia management need an improvement, but in our opinion, the most reasonable is to keep putting efforts into health education and improving community awareness, because prevention is always better than cure. This can be done by intensifying educational campaigns, establishing a long-term comprehensive educational program, and reaching the maximum number of individuals. The authors encourage innovative approaches like including modules in the school curriculum or organizing special classrooms, and broadcast short films or interactive theatre or plays. On the other hand, we also believe in initiating an appropriate and ethical dialogue with community leaders (religious or opinion leaders for example) in populations with cultural heritage to accept some medical practices and policies such as laboratory analysis, marriage screenings, and prenatal diagnosis, with respect to human dignity and rights.

In addition to prevention, it is necessary to consider the treatment of thalassemia, especially the most severe forms such as beta-thalassemia major. The conventional therapy includes regular blood transfusion and iron chelation, and certainly improves the quality of life of thalassemia patients but remains a life-long treatment. Today, allogeneic hematopoietic stem cell transplantation could offer a definitive cure for those patients. Another promising treatment is gene therapy, but this method is facing many technological and ethical issues and is still at the experimental stage.

In the nearest future, the authors do not expect the situation with thalassemia patients to improve radically because of the consequences of the COVID-19 pandemic, which has added more financial burden and posed more challenges to patients, communities, and already stretched health-care systems.

Note: International Thalassemia Day is marked on May 8 every year to raise awareness about this condition among the public across the globe.

Conclusion

Throughout history, several historical, social, and cultural factors have led to the spread of thalassemia in regions such as MENA, the Indian subcontinent, and Southeast Asia. In the last few decades, economic factors have increased this spread. The very important achievements today are still insufficient to eradicate the disease, so it is necessary to put more efforts on educating and raising awareness about the disease and to implement a more affordable thalassemia treatment in the future. The COVID-19 pandemic also stressed the necessity to increase the protection measures around thalassemia patients, who are a vulnerable group of individuals.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.