Indian sickle cell disease registry for surveillance and patient management: Development and implementation.

In India, sickle cell disease (SCD) predominantly occurs in indigenous (tribal) people, who are about 104 million. However, screening and diagnosis seldom happen. This situation necessitates developing a comprehensive SCD care model, including a registry. This paper describes the development and implementation of the Indian SCD registry (ISCDR) in six tribal-dominated districts of India. The ISCDR was created in two components-(i) an Android-based mobile/tablet application, (ii) a dashboard/admin panel for patients' data management and retrieval. Data capture involves two electronic case report forms (CRF), that is, the primary form (CRF-1) and the repeat visit form (CRF-2). CRF-1 is completed as soon as the patient is found positive and captures the patient's information, including medical history, diagnosis, symptoms, precipitating factors, hospitalisation history and treatment received. Issues related to quality, security and data-sharing were addressed. After the screening system was functional, ISCDR was initiated. In 12 months, data of 324 SCD patients and 1771 carriers were entered. The study demonstrates the feasibility of establishing an SCD registry in India. It collects systematic longitudinal data on SCD patients, which are essential for programme planning and management. Further, it is feasible to scale up and integrate with other health management databases.

Strengthening Health System and Community Mobilization for Sickle Cell Disease Screening and Management among Tribal Populations in India: An Interventional Study.

Sickle cell disease (SCD) affects 5% of the global population, with over 300,000 infants born yearly. In India, 73% of those with the sickle hemoglobin gene belong to indigenous tribes in remote regions lacking proper healthcare. Despite the prevalence of SCD, India lacked state-led public health programs until recently, leaving a gap in screening and comprehensive care. Hence, the Indian Council of Medical Research conducted implementation research to address this gap. This paper discusses the development and impact of the program, including screening and treatment coverage for SCD in tribal areas. With a quasi-experimental design, this study was conducted in six tribal-dominated districts in three phases - formative, intervention, and evaluation. The intervention included advocacy, partnership building, building the health system's capacity and community mobilization, and enabling the health systems to screen and manage SCD patients. The capacity building included improving healthcare workers' skills through training and infrastructure development of primary healthcare (PHC) facilities. The impact of the intervention is visible in terms of people's participation (54%, 76% and 93% of the participants participated in some intervention activities, underwent symptomatic screening and demanded the continuity of the program, respectively), and improvement in SCD-related knowledge of the community and health workers (with more than 50% of net change in many of the knowledge-related outcomes). By developing screening and treatment models, this intervention model demonstrated the feasibility of SCD care at the PHC level in remote rural areas. This accessible approach allows the tribal population in India to routinely seek SCD care at their local PHCs, offering great convenience. Nevertheless, additional research employing rigorous methodology is required to fine-tune the model. National SCD program may adopt this model, specifically for community-level screening and management of SCD in remote and rural areas.

Internal migrants' experiences with and perceptions of frontline health workers: A nationwide study in 13 Indian cities.

The role of frontline health workers is crucial in strengthening primary health care in India. This paper reports on the extent of services provided by frontline health workers in migrants' experiences and perceptions of these services in 13 Indian cities. Cluster random sampling was used to sample 51 055 households for a quantitative survey through interviewer-administered questionnaires. Information was sought on the receipt of health workers' services for general health care overall (from the head/other adult member of the household) and maternal and immunization services in particular (from mothers of children <2 years old). Purposively, 240 key informants and 290 recently delivered mothers were selected for qualitative interviews. Only 31% of the total respondents were aware of the visits of frontline health workers, and 20% of households reported visits to their locality during past month. In 4 cities, approximately 90% of households never saw health workers in their locality. Only 20% of women and 22% of children received antenatal care and vaccination cards from frontline health workers. Qualitative data confirm that the frontline health workers' visits were not regular and that health workers limited their services to antenatal care and childhood immunization. It was further noted that health workers saw the migrants as"outsiders." These findings warrant developing migrant-specific health-care services that consider their vulnerability and living conditions. The present study has implications for India's National Urban Health Mission, which envisions addressing the health care needs of the urban population with a focus on the urban poor.

Feasibility of population-based screening of sickle cell disease through the primary health care system in tribal areas of India.

OBJECTIVE: To describe the development and implementation of a population-based screening programme for sickle cell disease (SCD) implemented in 12 SCD-endemic and tribal-dominated primary/community health centres (PHCs/CHCs) across six districts of India. SETTING: India reports a huge burden of SCD, especially among indigenous (tribal) communities. However, there is no state-led SCD programme in many places, and systematic screening is absent. This situation necessitates developing a model of population screening. METHODS: This programme was meant to screen all people and was carried out in three tiers. The first tier was a symptomatic survey carried out by community health workers. Regular health workers then screened those referred by sickle cell solubility test at sub-health centres as the second tier. The third tier was confirmation by haemoglobin electrophoresis at PHCs/CHCs. Communities were mobilised and prepared to accept the screening. Capacity building of health facilities was ensured through training and supply of equipment and material. RESULTS: Initial observation based on six months' data revealed that out of the 110,754 tribal population of 12 PHCs/CHCs, 8418 (7.6%) were identified in the symptomatic survey. Subsequently, 9416 people, including the above 8418, underwent the solubility test, and 2607 (27.7%) were found to be positive. Of these, 1978 (78.9%) underwent electrophoresis. About 64.2% were found to be positive for sickle haemoglobin (233 (18.4%) SCD and 1036 (81.6%) SCD trait). CONCLUSIONS: The study demonstrates the feasibility of establishing a population-based screening programme in the primary health care system. It is easy to implement in tribal habitations as part of the proposed national SCD/haemoglobinopathies programme.

Sickle cell disease-related knowledge and perceptions of traditional healers in tribal communities in India: implications on sickle cell disease programme.

Sickle cell disease (SCD) is a progressively debilitating genetic disease, and India is the second most affected nation in the prevalence of births with SCD. This SCD prevalence is high among Indian indigenous tribal communities, whose healthcare is pluralistic. Traditional healers are an essential part of tribal pluralistic care. This study aimed to understand the extent of SCD-related knowledge and practices of traditional healers and their willingness to participate in the SCD programme, which is primarily meant to screen and treat SCD. Following the grounded theory approach, data were collected by in-depth interviews with 40 traditional healers selected from five SCD endemic districts. Text data were coded through a deductive approach, and thematic content analysis was carried out. A few healers knew about SCD. However, almost all are aware of anaemia and its symptoms. Most healers were unaware of the cause of SCD and mentioned that malnutrition and anaemia are reasons for the recurrence of SCD-related symptoms. Most of the traditional healers did not give any treatment. Some gave symptomatic treatment and provided herbal medicines along with some rituals. Though some healers treated some of the typical symptoms of SCD like spleen enlargement, jaundice, swelling and pains in joints, they did not link them with SCD. All traditional healers expressed concern and said they support the government-run SCD programme. The programme should recognise the role and importance of traditional healers. Necessary education on SCD may be given to the healers. Such involvement and education empower the healers in appropriately guiding the people concerning SCD care.

Peripheral health workers' knowledge and experience related to sickle cell disease: an in-depth interview study in six tribal-dominated districts of India.

This study reports the extent of sickle cell disease (SCD)-related knowledge and management practices of peripheral health workers located in tribal areas of India. This formative qualitative study used a grounded theory approach and collected data through in-depth interviews. It was implemented in six districts endemic to SCD. From each district, four primary health centre (PHC) areas, predominantly inhabited by tribal communities, were included. The participants were 120 peripheral health workers, in two categories-regular health workers (RHWs) and community health workers (CHWs), working in 24 PHCs. Most of the RHWs and a little lesser number of CHWs were aware of SCD, and most of them knew it as a blood disorder. About half of the health workers reported that SCD is hereditary; however, some attributed it to malnutrition and considered it anaemia. Many health workers could tell some typical symptoms of SCD, including anaemia and severe pain. None of the PHCs offered management/treatment of SCD. And none of the health workers has any expertise in managing SCD patients. However, some health workers dealt with SCD cases and provided symptomatic treatment. Though several health workers said that SCD is preventable, comprehensive knowledge on prevention was lacking. Some health workers mentioned mass screening, counselling, and creating awareness. Thus, this paper reports the inadequacy of SCD-related knowledge and management practices among health workers. Health workers should know their roles and capabilities in managing SCD. They should be provided in-service, regular, and structured training programmes as part of the comprehensive SCD programme.

Inclusive partnership and community mobilization approaches to improve maternal health care access among internal migrants in nine Indian cities.

Background: Disparities in healthcare access to internal migrants exist, and the gaps may widen further if appropriate steps are not taken. Innovative approaches are needed to better align the healthcare services with the migrants' needs. Aim: The aim was to develop and test a supportive strategy of healthcare, which would achieve the desired level of access and delivery of maternal healthcare services to internal migrants living in nine Indian cities. Methods: This intervention with the quasi-experimental design was conducted with pre- vs post-intervention comparisons within the interventional groups and with the control group. The intervention was implemented with an inclusive partnership approach. Advocacy and community mobilization were the main intervention components. Findings: An increased proportion of women sought antenatal care during the intervention. More women initiated seeking antenatal care in the first trimester. Due to intervention, health workers' prenatal (41.7% in the post- against 14.7% in the pre-interventional phase) and postnatal home visits increased (11.6% to 34.7%) considerably. Conclusions: Interventions with inclusive partnership would improve healthcare access to vulnerable communities such as migrants. Hence, efforts to strengthen the government healthcare system through novel strategies are crucial to provide better healthcare to migrants.

Inadequate community knowledge about sickle cell disease among the Indian tribal population: a formative assessment in a multicentric intervention study.

BACKGROUND: Sickle cell disease (SCD) is a serious public health problem, with >300 000 affected births worldwide each year. About 73% of the SCD-affected people in India belong to the tribal population. The Government of India is planning to implement a programme for SCD and hence people's knowledge of SCD is crucial. This paper reports the SCD-related knowledge among the Indian tribal population. METHODS: As part of a formative assessment before an intervention, data were collected from 9837 adults from 24 primary health centre areas of six states. Each community's knowledge of SCD was elicited through an interviewer-administered pretested questionnaire. Univariate and multivariate analyses were conducted. RESULTS: Overall, 32.1% (CI 31.2 to 33.1%) of participants had heard of SCD, 7.9% (CI: 7.3 to 8.4%) knew that SCD is hereditary, 19.4% (CI: 18.7 to 20.3%) knew that a blood test can diagnose SCD and 23.9% (CI: 23.1 to 24.8%) knew that SCD is treatable. Only 13.1% (CI: 12.4 to 13.8%) knew that SCD can be prevented. No more than 16% knew about any SCD symptoms. Multiple logistic regression revealed some predictors of basic knowledge (i.e. had heard of SCD). CONCLUSIONS: There is a gross inadequacy of knowledge about SCD in the Indian tribal population. This study warrants implementing a health education programme as a part of the SCD programme.

Improving the Capacity of Health System and Community for Sickle Cell Disease Screening and Management Among Tribal Population in India: Protocol of an Intervention Study.

Sickle cell disease (SCD) is one of the major public health problems in the world. In India, the burden of SCD is comparatively high in socio-economically disadvantaged tribal communities. Though efficacious interventions are available to manage SCD, they are not reaching to these communities and no comprehensive programme is in place in the health care system. Therefore, the Indian Council of Medical Research has initiated a nation-wide study to develop an effective intervention model for SCD patients in tribal areas through the government health care system. This intervention includes increasing awareness and preparing the communities for accessing the government health care system for SCD care, and improving the capacity of the primary health care systems including the training of the health care providers on prevention and management of SCD. The study adopted a quasi-experimental design with pre-vs. post-intervention comparisons of outcome variables within the interventional groups and with the control group. The study will be implemented in 6 districts which are endemic for SCD, spread across different geographical zones of India. In each district, four primary health centre (PHC) areas which are predominantly inhabited by tribal population will be selected. Of these four PHC areas, two will be selected randomly for implementing the intervention and the remaining two will be the control area. Information necessary for development and implementation of the intervention will be gathered during formative research, by using both quantitative and qualitative research methods. Intervention with an inclusive partnership and community mobilization will be implemented. The major steps in the implementation of intervention are partnership building with various health and non-health partners including the community. Capacity building and strengthening is another important component to enable the primary health facilities to screen and manage SCD patients. Primarily, sub-health centres and primary healthcare centres will be equipped with appropriate SCD screening techniques. All doctors in the system will be trained in advanced treatment and management issues. To improve the community's awareness and readiness, community mobilization activities will be conducted. An impact evaluation will be carried out at the end of the intervention by comparing the improvement of SCD management in intervention PHCs to that of the control PHCs. However, the process evaluation and necessary mid-term corrections will be made throughout the intervention period. Thus, an intervention model in terms of its suitability, replicability and sustainability for the tribal population will be developed and tested. The findings of this study are more suitable to use during advocacy and to replicate the model by the state health departments. This study develops and places an appropriate referral system for SCD patients at the PHC level. Improving the community's access to health care, improving the quality of care in government health centres and raising awareness among tribal communities are crucial to achieving through innovation. Taken together, these innovations would significantly contribute to better access to health care and management of the SCD patients of underserved tribal population.

Rosmarinus officinalis L. extract ameliorates intestinal inflammation through MAPKs/NF-κB signaling in a murine model of acute experimental colitis.

We investigated the anti-inflammatory and anti-colitis effects of Rosmarinus officinalis L. extract (RE) by using both in vitro LPS-activated mouse RAW 264.7 macrophages and in vivo dextran sulfate sodium (DSS)-induced experimental murine colitis and suggested the underlying possible mechanisms. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was performed to identify the major components present in the RE. The clinical signs, biochemistry, immunoblot, ELISA and histology in colon tissues were assessed in order to elucidate the beneficial effect of RE. RE suppressed the LPS-induced pro-inflammatory cytokine production and the expressions of inflammatory proteins in macrophages. Administration of RE (50 and 100 mg kg(-1)) also significantly reduced the severity of DSS-induced murine colitis, as assessed by the clinical symptoms, colon length and histology. RE administration prevented the DSS-induced activation of p38, ERK and JNK MAPKs, attenuated IκBα phosphorylation and subsequent nuclear translocation and DNA binding of NF-κB (p65). RE also suppressed the COX-2 and iNOS expressions, decreased the levels of TNF-α and IL-6 cytokines and the myeloperoxidase activity in the colon tissue. Histological observation revealed that RE administration alleviated mucosal damage and inflammatory cell infiltration induced by DSS in the colon tissue. Hence, RE could be used as a new preventive and therapeutic food ingredient or as a dietary supplement for inflammatory bowel disease.

Oral administration of geraniol ameliorates acute experimental murine colitis by inhibiting pro-inflammatory cytokines and NF-κB signaling.

Ulcerative colitis is associated with a considerable reduction in the quality of life of patients. The use of phyto-ingredients is becoming an increasingly attractive approach for the management of colitis. Geraniol is a monoterpene with anti-inflammatory and antioxidative properties. In this study, we investigated the therapeutic potential of geraniol as a complementary and alternative medicine against dextran sulphate sodium (DSS)-induced ulcerative colitis in mice. Disease activity indices (DAI) comprising body weight loss, presence of occult blood and stool consistency were assessed for evaluation of colitis symptoms. Intestinal damage was assessed by evaluating colon length and its histology. Pre-treatment with geraniol significantly reduced the DAI score, improved stool consistency (without occult blood) and increased the colon length. The amount of pro-inflammatory cytokines, specifically TNF-α, IL-1ß and IL-6 and the activity of myeloperoxidase in colon tissue were significantly decreased in geraniol pre-treated mice. Western blot analyses revealed that geraniol interfered with NF-κB signaling by inhibiting NF-κB (p65)-DNA binding, and IκBα phosphorylation, degradation and subsequent increase in nuclear translocation. Moreover, the expressions of downstream target pro-inflammatory enzymes such as iNOS and COX-2 were significantly reduced by geraniol. Pre-treatment with geraniol also restored the DSS-induced decline in antioxidant parameters such as reduced glutathione and superoxide dismutase activity and attenuated the increase in lipid peroxidation marker, thiobarbituric acid reactive substances and nitrative stress marker, nitrites in colon tissue. Thus, our results suggest that geraniol is a potential therapeutic agent for inflammatory bowel disease.

Role of HLA class II loci polymorphism in the manifestation of type 1 diabetes in a Bengali Indian patient population.

To assess the contribution of the HLA class II region for susceptibility to type 1 diabetes mellitus (T1DM), we investigated the association of HLA class II alleles-DP, DQ, and DRB1. Here, we present an extensive molecular typing for HLA class II alleles and their haplotypes in a Bengali-speaking Indian population of T1DM patients (n=151) and controls (n=151) from West Bengal. HLA typing was done by DNA sequencing using a 3730 DNA Analyzer. The individual analysis of each gene gave the following alleles to be higher in cases than in controls, thus making them susceptible alleles-DPA1*020103, DPB1*020102, DQA1*050101, DQA1*0201, and DQB1*020101G. Similarly, the following alleles are protective alleles in our study-DPA1*010602, DPB1*040101, DQA1*010201, DQA1*0103, and DRB1*15. Our result confidently establishes that HLA-DP allelic, and its haplotypic, diversity contributes significantly to the risk for T1DM. The DQA1*0103 allele is a novel allele with a significant association with the protection from T1DM. Among the various haplotypes tested, the DQA1*0201:DQB1*020101G, DQA1*050101:DQB1*020101G, and DQA1*0201:DQB1*030101G were the most frequently found in T1DM patients. In India, very few investigations have been undertaken to study the impact of the genetic background on the risk to develop T1DM in its population, where the annual average incidence is 10.5/100,000/year. In conclusion, the present study highlights the genetic effect of HLA haplotypes that contributes to the susceptibility to T1DM.

Polymorphisms in the IRS-1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women.

Polycystic ovary syndrome is known to be characterized by metabolic abnormalities such as hyperinsulinemia, adiposity and dyslipidemia. Both insulin receptor substrate-1 and peroxisome proliferator-activated receptor-γ have emerged as significant candidate genes in the pathogenesis of PCOS. In this study, we report for the first time, the association pattern of these genes with PCOS among South Indian women. Two hundred fifty PCOS cases and 299 controls were sequenced for IRS-1 exon1 and PPAR-γ exon 2 and exon 6 to study the already reported SNPs in other ethnic groups and to identify any novel SNP in these exonic regions specific to the Indian population. We did not find any novel SNP in our population except for those already reported- two IRS-1 polymorphisms (Gly972Arg and G2323A) and two PPAR-γ polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR-γ exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p≤0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR-γ haplotypes with mutations depicted reduced frequency of hyperandrogenic and metabolic traits in PCOS compared to the haplotype with only wild type alleles. Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR-γ is reaffirmed in our study.