Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India

Jain, Dipty; Arjunan, Aishwarya; Sarathi, Vijaya; Jain, Harshwardhan; Bhandarwar, Amol; Vuga, Marike; Krishnamurti, Lakshmanan

doi:10.1002/pbc.26085

Cited by 12 publications

(5 citation statements)

References 37 publications

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“…These advances appeared to be associated with a reduction in mortality [ 59 , 62 ] and stroke incidence in children appeared to decrease in some regions of the USA and Europe during the 1980s and 1990s [ 24 , 37 , 62 , 64 ] ( Figure 1 A). However, despite newborn screening, the overall incidence in childhood in other areas was similar to that reported previously [ 2 , 27 ], with 0.67/100 PYO at the Children’s hospital of Philadelphia from 1990 to 1998 [ 65 ], 0.85/100 PYO in the Dallas cohort from 1983 to 2002 [ 59 ], 0.88/100 PYO in Northern California from 1991 to 1998 and 0.8/100 PYO in Nagpur, India from 2008 to 2012 [ 66 ] ( Figure 1 A).…”

Section: Strokesupporting

confidence: 87%

Epidemiology of Stroke in Sickle Cell Disease

Kirkham

Lagunju

2021

JCM

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Sickle cell disease is the most common cause of stroke in childhood, both ischaemic and haemorrhagic, and it also affects adults with the condition. Without any screening or preventative treatment, the incidence appears to fall within the range 0.5 to 0.9 per 100 patient years of observation. Newborn screening with Penicillin prophylaxis and vaccination leading to reduced bacterial infection may have reduced the incidence, alongside increasing hydroxyurea prescription. Transcranial Doppler screening and prophylactic chronic transfusion for at least an initial year has reduced the incidence of stroke by up to 10-fold in children with time averaged mean of the maximum velocity >200 cm/s. Hydroxyurea also appears to reduce the incidence of first stroke to a similar extent in the same group but the optimal dose remains controversial. The prevention of haemorrhagic stroke at all ages and ischaemic stroke in adults has not yet received the same degree of attention. Although there are fewer studies, silent cerebral infarction on magnetic resonance imaging (MRI), and other neurological conditions, including headache, epilepsy and cognitive dysfunction, are also more prevalent in sickle cell disease compared with age matched controls. Clinical, neuropsychological and quantitative MRI screening may prove useful for understanding epidemiology and aetiology.

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Section: Strokesupporting

confidence: 87%

Epidemiology of Stroke in Sickle Cell Disease

Kirkham

Lagunju

2021

JCM

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“…This reinforces the importance of regional context in analysis of SCD mortality as well the significance of longitudinal studies over time. For instance, extreme weather conditions and rainy season are likely to cause higher morbidity and mortality among children in India, implying regional variations ( 30 , 31 , 32 ). Despite robust evidence about gendered inequalities in nutrition, access to healthcare and related higher infant/female mortality ( 10 ), a gender bias is not consistent in our and other hospital-based studies.…”

Section: Discussionmentioning

confidence: 99%

“…As an increasing number of children with SCD are surviving into adulthood, we argue for a shift in policy focus to improving long -term clinical care and supporting their educational and employment needs. New-born screening alongside an intensive follow-up care plan have shown promising results both at GMCH Hospital, Nagpur ( 30 , 40 ) and in some of the remote, rural adivasi areas such as Gudalur ( 27 ) and South Gujarat ( 25 ) as elsewhere in low and middle income countries across the world ( 41 ). Digital technology, remote clinical networks and better professional and patient education can all contribute to improving outcomes of care, as highlighted recently by the Lancet Hematology Commission on SCD ( 2 ).…”

Section: Concluding Observationsmentioning

confidence: 99%

A social profile of deaths related to sickle cell disease in India: a case for an ethical policy response

Chattoo,

Jain,

Nashine

et al. 2023

Front. Public Health

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India accounts for 14.5 percent of the global SCD newborns, roughly over 42,000 a year, second to sub-Saharan Africa. Despite the availability of cheap diagnostic and treatment options, SCD remains a largely neglected disease within healthcare policy and practice. Epidemiological modeling based on small, often dated, regional studies (largely from sub-Saharan Africa) estimate that between 50 and 90 percent of affected children will/die before the age of 5 years. This premise, coupled with targets of reducing under 5 mortality (SDG 4), privileges public health interventions for screening and prevention of new births, undermining investments in long-term health and social care. This paper presents a retrospective, descriptive analysis of the socio-demographic profile of 447 patients diagnosed with sickle cell or sickle-beta thalassemia, who died following admission at a tertiary care entre in India. We used anonymized hospital records of 3,778 sickle cell patients, admitted in pediatric and adult/medical wards between January 2016 and February 2021. A majority of hospital deaths occurred in the second and third decades of life, following a hospital admission for a week. The overall mortality during 2016–2019 was 14% with little gender difference over time. Contrary to our expectations, the number of hospital deaths did not increase during the first year of the COVID-19 pandemic, between 2020 and 2021. The conclusion highlights the importance of longitudinal, socio-demo-graphic data on deaths as providing important insights for identifying ethical policy interventions focused on improving SCD outcomes over time, reducing inequities in access to care, and preventing what might be considered “excess” deaths.

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“…However, decades of controlled clinical research have shown that HU, a potent ribonucleotide reductase inhibitor, is both safe and efficacious for SCA and leads to reduced morbidity and mortality, leading to its increasing use to treat both children and adults with SCA in high-resource countries as well as Africa and India. 4 , 7 , 8 , 9 , 10 , 11 , 12 Long-term administration of HU for patients with SCA induces the production of fetal hemoglobin (HbF), which inhibits erythrocyte sickling, improves red cell rheology, and increases red blood cell lifespan. 13 The regions of sub-Saharan Africa and India with a high incidence of SCA are also associated with the highest malaria burden.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous adjunctive treatment of malaria and its coevolved genetic disorder sickle cell anemia

et al. 2023

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Effective treatments for genetic disorders that co-evolved with pathogens require simultaneous betterment of both conditions. Hydroxyurea (HU) offers safe and efficacious treatment for sickle cell anaemia (SCA) by reducing clinical complications, transfusions, and death. Despite concerns that HU-treatment for SCA would increase infection risk by the human malaria Plasmodium falciparum, (the genetic driver of the sickle mutation), HU instead reduced clinical malaria. We utilized physiologically relevant drug exposures that mimic in vivo pharmacokinetics in humans. Under these conditions, we showed that HU and other ribonucleotide reductase (rnr) inhibitors, have significant, intrinsic killing activity in vitro against schizont stages of P. falciparum in both normal and sickle red blood cells. Long-term in vitro selection with HU increased expression of Pfrnr genes but showed low risk of eliciting stably resistant parasites or compromising potency of current antimalarial drugs. Additive activity devoid of antagonism by HU was observed with a wide spectrum of commonly used antimalarial treatments. These data endorse broad, safe, long-term use of HU for SCA in malaria endemic countries and provide a novel biological model for treatment of a genetic disorder with simultaneous, adjunct therapy of a life-threatening infection needed in a global health setting.

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Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India

Abstract: SCD-related complications are more frequent in Indian children than that observed in CSSCD. Further study is indicated to define SCD phenotype in India.

Cited by 12 publications

References 37 publications

Epidemiology of Stroke in Sickle Cell Disease

Epidemiology of Stroke in Sickle Cell Disease

A social profile of deaths related to sickle cell disease in India: a case for an ethical policy response

Simultaneous adjunctive treatment of malaria and its coevolved genetic disorder sickle cell anemia

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