Burden of sickle cell disease in tribal students in Maa-Baadi institutions in southern Rajasthan - A pilot study

Among the infectious agents, malaria parasite has foisted the most genetic pressure on human populations1. J.B.S. Haldane in 1949 argued that this genetic pressure could lead to a high incidence of genetic blood disorders in malaria-endemic areas2. This theory is now widely recognised for a range of mutations affecting the alpha or beta globin genes that synthesis haemoglobin (haemoglobinopathies), those accountable for sickle cell anaemia, haemoglobin-C, haemoglobin-E, and the alpha and beta thalassaemias3.

Sickle cell disease (SCD), an inherited haemoglobin disorder is characterized by predominance of abnormal haemoglobin (HbS) in the erythrocytes. It is an autosomal genetic disorder caused by a substitution mutation at the sixth position of β-globin with the replacement of glutamic acid by valine4. SCD has been reported as a worldwide community health problem by the World Health Organization5. Every year, more than 0.3 million children with homozygous SCD are born globally5. The study by Piel et al6 revealed that majority of these children belonged to low- and middle-income countries. SCD has remarkable public health implications and early childhood mortality can be reduced if diagnosed at birth, and appropriate healthcare interventions are provided for children less than five years of age7,8.

The tribal population in the scheduled geographical area resides in forests and hilly terrains with difficult accessibility. SCD has emerged as one of the notable public health concerns affecting these indigenous groups. Studies by the Anthropological Survey of India9,10 reported the distribution and frequency of the sickle cell trait which reaches levels as high as 35 per cent in some of the tribes. Studies have also reported that the prevalence of sickle cell trait in the country ranges from 10 to 40 per cent11. However, the data on sickle cell disorder in Rajasthan are scanty. In Rajasthan, there are 12 Scheduled Tribes that constitute 13.5 per cent of the State’s population12. The common tribes are Bhil, Meena, Garasia and Damor.

The present study was intended to determine the prevalence of sickle cell disorder among the tribal students of southern Rajasthan and to estimate the burden of the disease community wise.

Material & Methods

Study sites and demography: This study was undertaken by the ICMR-National Institute for Implementation Research on Non-Communicable Diseases (NIIRNCD), Jodhpur, Rajasthan, India, in the scheduled areas of Rajasthan. The study was approved by the Institutional Ethics Committee for Research on human subjects. A written informed consent was obtained for all participants (4-18 yr) from teachers, wardens and guardians and assent from the eligible participants (7-18 yr). The ethical issues were addressed according to the principles expressed in the Declaration of Helsinki. The criteria used for selecting scheduled area included percentage of the tribal population to the total population and the compactness and size of the tribal population. The scheduled area of Rajasthan includes Pratapgarh, Banswara, Dungarpur, Udaipur (partial) and Abu Road block of Sirohi districts (Table I).

Sampling method: Among the 33 districts of Rajasthan, five districts were selected for the study. These five districts were selected because in these districts, more than 50 per cent population was tribal. Further, only those sub-districts in each district were selected where tribal population proportion was more than 50 per cent. The students of all the Maa-Baadis and schools in the sub-districts were approached to participate in the study.

Programme development: The Ministry of Tribal Affairs, Government of India, New Delhi, had developed a programme through which it desired to establish a database on the occurrence of SCD and sickle cell trait (SCT) among the tribal population of India in collaboration with the Indian Council of Medical Research (ICMR), New Delhi, Department of Health Research (DHR), Ministry of Health and Family Welfare, Government of India. The ICMR-NIIRNCD, Jodhpur (erstwhile Desert Medicine Research Centre) is one of the institutes under the aegis of the ICMR situated in Rajasthan and initiated a joint programme with Medical and Health Department of the five districts for the screening of the SCD among the school going children. The research team of the ICMR-NIIRCD, Jodhpur, visited each of the districts and trained medical officers, technicians and paramedical staffs pertaining to the testing of sickle cell (solubility test), symptoms, basic treatment and intervention for the diseased person suffering from a sickle cell disorder. Genetic counselling was provided to the adult students, teachers and parents of the children with SCD and SCT.

Procedure followed for the screening: All students who gave their assent and written consent to participate in the study were enrolled for the study. The demographic information of the students was provided by teachers in the Maa-Baadi (4-10 yr) centres and in the hostel (11-18 yr) by the project staff. Those with any previous history of blood transfusion were excluded from the study. Twenty microliters of blood was taken from each student of the targeted population for the solubility test and another 20 µl for haemoglobin estimation. However, 40 µl of blood was taken from those found to be anaemic (Hb lower than 7 g/dl). The solubility test was conducted as per the methodology of Surve et al13. Additional 2 ml peripheral blood was taken from individuals positive for the solubility test. Blood samples were collected in vacutainers containing EDTA and were transported to the institute under cold chain.

Confirmatory test: Cellulose acetate electrophoresis-based test was used for confirmation of the diagnosis. The test was conducted in the Biochemistry Laboratory of ICMR-NIIRCD.

Sickle status card: All selected students were screened for SCD/SCT and issued genetic counselling card for the purpose of generating awareness of the tribal people regarding the SCD and take appropriate action to prevent the disease.

Results

The overall prevalence of SCD was 5.8 per cent in the five tribal sub-plan districts of Rajasthan. Among the positive SCD cases, 5.61 per cent were prevalent heterozygous and 0.17 per cent were prevalent homozygous. The prevalence of SCD was 10.5 per cent in the Sirohi district, which was highest among all the study districts. This was followed by Banswara (7.42%) and Udaipur (6.53%). The prevalence of SCDs in Dungarpur and Pratapgarh districts was 1.89 and 5.51 per cent, respectively (Table I). Out of 2132 SCD-suspected cases, 729 were recorded from Banswara district and were maximum among five districts. When the prevalence was compared among the sub-districts of Udaipur, Kotda sub-districts had the utmost prevalence of 14.49 per cent (Figure). Similarly in the Banswara district, Sajjangarh sub-district was with the highest prevalence of SCD (12.28%).

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Figure

Prevalence of the disease in the five districts (23 sub-districts) of the tribal sub-plan area (ArcGIS software).

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Furthermore, the highest prevalence of SCD was reported among the individuals belonging to the Garasia tribe which was 13.81 per cent (Table II). Among the informants belonging to Bhil tribe, the prevalence of SCD was 6.93 per cent. However, the occurrence of SCD in Meena tribe was lower than Garasia and Bhil tribes and the prevalence was 3.25 per cent. Participants from Bhil and Meena tribes were present in all the five study districts, whereas participants of Garasia tribe were present only in the Kotda block (14.27%) of Udaipur district and Abu Road block (12%) of Sirohi district. Furthermore, the prevalence of SCD in Kathodi tribes was 8.41 per cent (Table II).

The prevalence of homozygous SCD cases was found to be equal in the males and females of the study population. However, the prevalence of SCD was higher in the Garasia tribes. All the SCD cases of the Udaipur and Abu Road block of Sirohi districts were of Garasia tribes and their prevalence was 13.81 per cent. All the sickle cell positive cases of the Udaipur district were from the Kotda sub-districts. A total of 2150 SCD-negative samples were collected for confirmation of the solubility test followed by paper electrophoresis. All the cases were found to be SCD negative but were haemoglobin D positive as per the cellulose acetate electrophoresis banding pattern. During the study, 172 cases of the HbD (Punjab) were reported, the district-wise distribution is mentioned in Table III.

Discussion

Every year more than seven million infants are reportedly born globally with either a congenital aberration or a genetic disease14. Of the haemoglobinopathies, SCD is of major concern for community health. SCD patients require immediate attention due to its acute as well as chronic complications, including painful vaso-occlusive episodes, cerebral vasculopathy, chronic kidney disease, priapism, acute chest syndrome, pulmonary hypertension and bacterial infectivity among others15-17. The burden of infectious diseases are a major concern in tropical countries and substantial attempts are currently being made to minimize the same. Because of their global burden and priority for treatment among policymakers, malaria, tuberculosis and HIV, the load of birth defects has largely been neglected. The WHO has invited African nations to tackle the growing burden of SCA5,18, but SCA persists a low importance compared with other health problems19. However, at present priority has been assigned to control the birth defect disease, particularly sickle cell anaemia in India20. The tribal population constitutes nearly 8.2 per cent of the country’s population. The sickle cell gene is found predominantly in the tribal population of Gujarat, Maharashtra, Madhya Pradesh, Chhattisgarh and Odisha21.

An approximate number of sickle heterozygotes (AS) and homozygotes (SS) were estimated in 1988 as 2,434,170 and 121,375, respectively, in India9. As per the estimate by Rao9, 50 per cent of the entire AS and SS neonates are born in primarily three countries, viz. Nigeria, the Democratic Republic of the Congo and India. For the case of sickle homozygous neonates, the estimate for India was 42016, which resembles 88 per cent of the homozygous instances in Asia9. In the present study, 36,752 students were screened and the prevalence of SCD/SCT was reported at the village level in the tribal sub-plan region of Rajasthan. Mandot and Ameta22 screened a total of 1090 children belonging to Garasia tribe in Sirohi district of Rajasthan and the prevalence of sickle cell disorder reported by them was 8.53 per cent. Wherein 0.77 per cent were homozygous (HbSS) and 7.7 per cent were heterozygous (HbAS) which was comparatively lower than that in the present study. On the other hand, Majumdar and Majumdar23 screened 1524 tribal population of Dahod district (Northern Rajasthan) for SCD and recorded 11 per cent trait (heterozygous) and 0.5 per cent disease (homozygous) in a hospital-based study. The percentage of traits and diseases was higher than our study. However, the hospital cohort was not segregated into different tribes in the article and the higher percentage may be because it was a hospital based study. Patel et al24 screened the 168,495 tribal population of Gujarat and recorded 11.3 per cent SCT and 0.57 per cent SCD. The tribal population included in the study were residing in the western and southern parts of Gujarat. Furthermore, the prevalence of SCD was more in the tribal population of Gujarat than that of Rajasthan. Andrew et al25 recorded one per cent prevalence of SCT in the Garasia tribes and 4.4 per cent in Bhil tribes which is lower than the present study. The results of the study showed the prevalence of SCD in the region and lead the policymakers to undertake clinical investigations among the homozygous cases. This is a community-based study and covered all the five districts predominantly inhabited by the tribal population, which is the strength of the study. However, we could not screen the children not attending schools and Maa-Baadis. Also, other congenital haemoglobinopathies could not be included in this study which was weakness of the study. Despite the limited permission from the Tribal Area Development Department, more than 37000 subjects were screened for detecting those heterozygous and homozygous for the sickle cell gene. As a consequence of the study, neonatal screening has been initiated in the tribal region through the National Health Mission.

Overall, the findings of this study suggest that SCD is a major haemoglobinopathy among the tribal people of Rajasthan. Health education and counselling should be given to the carriers of the HbS gene, and this may eventually influence arranged marriages and consequently the reproductive decisions.