Indian J Med Res 151, April 2020, pp 326-332 Quick Response Code:

DOI: 10.4103/ijmr.IJMR_1946_18
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+
Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

Homozygous sickle cell disease in Central India & Jamaica: A

comparison of newborn cohorts

Dipty Jain1, Rajini Tokalwar2, Dipti Upadhye3, Roshan Colah3,† & Graham Roger Serjeant4
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

1
Department of Pediatrics, Government Medical College, 2Department of Pediatrics, Indira Gandhi Medical
College, Nagpur, 3National Institute of Immunohaematology, KEM Hospital, Mumbai, Maharashtra, India &
4
Sickle Cell Trust (Jamaica), Kingston, Jamaica

Received October 23, 2018

Background & objectives: Homozygous sickle cell (SS) disease in Central India runs a more severe clinical
course than reports from other areas of India. The current study was undertaken to compare the disease
in Central India (Nagpur) with that in Jamaica, both populations defined by newborn screening.
Methods: The Nagpur cohort included infants born to sickling-positive mothers from May 2008 to 2012,
examined by high-pressure liquid chromatography and DNA analysis. The Jamaican cohort screened
100,000 consecutive non-operative deliveries between June 1973 and December 1981, analyzed by
haemoglobin (Hb) electrophoresis and confirmed by family studies and compatible HbA2 levels.
Results: In Nagpur, 103 SS patients were detected, but only 78 (76%) were followed up. In Jamaica, 311
cases were followed from birth and compliance with follow up remained 100 per cent up to 45 years.
In the Nagpur cohort all had the Asian haplotype, and 82 per cent of Jamaicans had at least one Benin
chromosome; none had the Asian haplotype. Compared to Jamaica, Nagpur patients had higher foetal
Hb, less alpha-thalassaemia, later development of splenomegaly and less dactylitis. There were also high
admission rates for febrile illness and marked anaemia. Invasive pneumococcal disease occurred in
10 per cent of Jamaicans but was not seen in Nagpur.
Interpretation & conclusions: There were many differences between the disease in Nagpur, Central India
and the African form observed in Jamaica. The causes of severe anaemia in Nagpur require further
study, and reticulocyte counts may be recommended as a routine parameter in the management of SS
disease. The role of pneumococcal prophylaxis needs to be determined in Nagpur patients. Future studies
in India must avoid high default rates.

Key words Anaemia - Central India - foetal haemoglobin - Jamaica - newborn cohort - sickle cell disease - splenomegaly

Former Director-in-Charge
†

© 2020 Indian Journal of Medical Research, published by Wolters Kluwer - Medknow for Director-General, Indian Council of Medical Research
326
 JAIN et al: SICKLE CELL DISEASE IN INDIA & JAMAICA 327

An early comparison of homozygous sickle cell (Sysmex K-1000, Sysmex Corporation, Kobe, Japan)
(SS) disease in the State of Odisha, India, and Jamaica and HbA2 and HbF levels estimated by HPLC.
concluded that Odisha patients had more frequent
alpha-thalassaemia, higher foetal haemoglobin (HbF) In Jamaica, umbilical cord samples were collected
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+

and lower HbA2 levels, higher total haemoglobin (Hb), into EDTA and analyzed by electrophoresis on cellulose
Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

microcytic red cell indices and lower reticulocyte acetate followed by acid agar gel electrophoresis of all
counts compared to Jamaicans1. Clinically, Odisha electrophoretically abnormal bands9, and the diagnosis
patients had greater persistence of splenomegaly, and was confirmed by consistent HbA2 levels, and family
possibly splenic function, frequent bone pain, but less studies. Haematological indices were determined
chronic leg ulceration and priapism. Broadly, similar electronically10 (Coulter Counters, Hialeah, Florida),
conclusions were later drawn from a population in HbA2 by elution after alkaline Hb electrophoresis and
Gujarat2 but that study found more severe disease in HbF by alkali denaturation.
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

Central India, an impression since amply confirmed3-6. Comparison of Nagpur and Jamaican data:
This raises two issues, the mechanism of the difference Molecular, clinical and haematological data of Nagpur
between mild and severe disease in India and also how cohort were compared with the Jamaican cohort10.
the more severe disease in Central India compares The relatively small numbers and narrow age range
with those of African origin in Jamaica. The current of the Nagpur group implied that comparisons with
study was undertaken to address the latter question Jamaican data were usually confined to the first three
and was based on populations diagnosed by newborn years of life for haematology and clinical indices. For
screening in Nagpur7 and Jamaica8 which avoided the Hb and red cell indices, Nagpur data were restricted
symptomatic bias inherent in clinic-based populations. to steady-state outpatient visits excluding values
Material & Methods on hydroxyurea and for three months following
transfusion. Reticulocyte counts in Nagpur were
Patient ascertainment: The Nagpur cohort study5,7 uncommon but routine in Jamaica. Where multiple
was based on newborn screening at the Government observations were available in Nagpur, only that
Medical College, Nagpur, between May 11, 2008 and closest to the target age was used whereas Jamaican
May 15, 2012. The offspring of mothers with positive data were the mean of all steady state observations
solubility tests had heel-prick samples taken into for each age group. Beta-globin haplotypes were
ethylenediaminetetraacetic acid (EDTA) 1-7 days determined in Jamaicans11 and Nagpur5 as specified.
after birth and analyzed by high-performance liquid The presence of alpha-thalassaemia was determined
chromatography (HPLC) (Bio-Rad Laboratories, USA). by multiplex gap-polymerase chain reaction in Nagpur
There were 103 infants with SS disease, of whom patients and by restriction endonuclease analysis of
25 defaulted at birth and the current study was confined peripheral blood DNA in Jamaica12.
to the 78 SS infants with follow up. Scheduled Castes
(SCs) accounted for 69 (88%) among whom the Mahar Procedure for follow up: Nagpur patients were
dominated and only three were Scheduled Tribes given regular appointments, and defaulters were
(STs). The Jamaican cohort8 recruited 311 infants with pursued by phone calls, letters and social workers.
SS disease during screening of 100,000 consecutive The protocols required pneumococcal prophylaxis
non-operative deliveries at Victoria Jubilee Hospital with oral penicillin and the 23-valent pneumococcal
in Kingston, Jamaica, between June 25, 1973 and vaccine (costs covered by the study funders), and the
December 28, 1981. The current study of Nagpur conjugate vaccine was recommended (course cost
and Jamaican data involved reanalysis to make the ₹16,000/- charged to the patient). Hydroxyurea (10 mg/
group data comparable and was conducted between kg) was used in four patients. For Jamaican patients,
November 2017 and October 2018. the follow up schedule was monthly for the first six
months, alternate months from 6 to 12 months and
Genotype diagnostic criteria: In Nagpur, the diagnosis three monthly thereafter. From 1983, pneumococcal
of SS disease was based on a single-dominant band in prophylaxis was provided by monthly injection
the position of HbS on HPLC, consistent HbA2 levels of depot penicillin from four months to four years
and family studies. In the 78 newborns with some and pneumococcal vaccine (initially, the 14-valent
follow up, both parents had the SS gene in 59 (76%). vaccine, later the 23-valent vaccine at two years); all
Haematological indices were determined electronically patients completed the first four year high-risk period
 328 INDIAN J MED RES, APRIL 2020

before the advent of conjugate vaccine. None received Table I. Distribution of alpha‑ and beta‑globin haplotypes in
hydroxyurea. Patients were encouraged to follow this the two populations
schedule when perfectly well and to attend at any Globin genotype Jamaica Nagpur
time when sick; computerized reminders were sent
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+

(n=311) (n=103)
followed by home visits, if necessary.
Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

Alpha‑globin genotype
Analyzed 272 (87.5%) 73 (70.9%)
Statistical analysis: Normally distributed data were
αα/αα 172 61
compared by means and standard deviations. HbF
distributions were skewed and transformed using α−3.7
/αα 91 7
the formula loge (HbF+4). The difference in alpha- α−3.7/α−3.7 9 0
thalassaemia frequency between populations was α−4.2
/αα 0 4
tested by Fisher’s exact test, and any influence of α−3.7/α−4.2 0 1
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

alpha-thalassaemia on the prevalence of bone pain, Beta‑globin genotype

fever, and anaemia in the Nagpur dataset was tested by Analyzed 213 (68.5%) 74 (71.8%)
the incidence rate ratio (IRR) after Poisson regression
Benin/Benin 123 0
of event counts.
Benin/Bantu 35 0
Results Benin/Senegal 17 0
Crossovers 36 0
Compliance with follow up: Of the 103 Nagpur infants,
Bantu/Bantu 1 0
25 defaulted at birth, 12 within one year and a further
10 within two years. This left 56 followed over two Senegal/Senegal 1 0
years, with an average follow up of 4.3 yr (median Asian/Asian 0 73
4.3 yr, range 2.0-8.7 yr), of whom 25 were seen within Asian/Bantu A2 0 1
the previous year. In Jamaica, 201 patients left the study
(121 deaths and 80 emigrated) leaving 110 survivors
resident in Jamaica, of whom there has been 100 per
(­P<0.01) as compared to Jamaica. The presence of
cent follow up for 37-45 years.
alpha-thalassaemia did not influence the prevalence of
Attendances and admissions: Among the 78 Nagpur admissions in Nagpur for bone pain [IRR: 1.52; 95%
patients with some follow up, there were 770 clinic confidence interval (CI): 0.43, 5.32; P=0.52], fever
visits (mean 9.9, range 1-36). Forty one patients had (IRR: 0.64; 95% CI: 0.24, 1.74; P=0.38) or anaemia
no admissions, but the remaining 37 patients had 157 (IRR: 1.58; 95% CI: 0.34, 7.29; P=0.56). All Nagpur
admissions (mean 4.2, range 1-17). The three most patients had the Asian haplotype, which did not occur
common clinical diagnoses at admission were fever in the Jamaica sample.
(38), bone pain (28) and anaemia (25).
Higher foetal haemoglobin (HbF) and HbA2 levels: In
Interventions: Of the 78 Nagpur patients, 61 (84%) Nagpur, HbF levels were consistently and significantly
received oral penicillin from a mean age of 0.9 yr higher than Jamaicans at ages 1-3 yr (Table II). HbA2
(range 0.2-2.7 yr) and conjugate vaccine was given levels were consistently lower at ages one, two, and
in eight. Four were treated with hydroxyurea starting three years in Nagpur, but the differences did not reach
at a mean age of 4.6 yr. In Jamaica, the interventions
significance.
changed with time as more data became apparent;
pneumococcal prophylaxis became routine around
Haematological indices: There were no significant
198413 and teaching parents splenic palpation from
differences in total Hb or mean cell Hb (MCH) at
198514. Hydroxyurea was not used in the first 25 years
of the study. ages 1-3 yr (Table II). Conclusions on reticulocyte
distributions were limited by a few observations in
Molecular findings: Alpha-thalassaemia in Jamaica Nagpur, but the mean values of 4.3, 6.3 and 7.0 per
was entirely of the α−3.7 type whereas the α−4.2 mutation cent at ages one, two and three years were consistently
occurred on four occasions in Nagpur (Table I); lower than 9.1, 11.9 and 12.7 per cent in the Jamaican
alpha-thalassaemia was less frequent in Nagpur cohort10.
 JAIN et al: SICKLE CELL DISEASE IN INDIA & JAMAICA 329

Table II. Comparison of some haematological features between the two cohorts
HbF (untransformed Jamaica15 Nagpur (unpublished data) Mean difference when P
mean %) transformed, 95% CI
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+

One year 15.5 25.2 2.51, 2.35‑2.68 <0.001

Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

Two years 12.1 22.5 2.58, 2.42‑2.73 <0.01

Three years 11.2 22.0 0.89, 0.18‑1.60 <0.05
Jamaica 15
Nagpur (unpublished data) Mean difference P
n Mean±SD n Mean±SD
Total Hb (g/dl)
One year 140 7.9±1.6 44 8.37±1.22 0.47, −0.05‑0.99 0.08
Two years 125 7.9±1.5 30 7.93±0.83 0.03, −0.53‑0.59 0.92
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

Three years 97 8.0±1.4 16 8.27±0.58 0.27, −0.44‑0.98 0.45

MCH (pg)
One year 140 24.2±3.5 32 23.4±3.9 −0.80, −2.18‑0.58 0.26
Two years 125 25.2±3.4 10 24.7±2.8 −0.50, −2.69‑1.69 0.65
Three years 97 27.1±3.6 8 25.4±2.1 −1.70, −4.27‑0.87 0.19
Hb, haemoglobin; HbF, foetal Hb; CI, confidence interval; MCH, mean cell Hb; SD, standard deviation

Anaemia and transfusions: In Nagpur, 26 (33%) patients 2.1 and 2.5 yr, the other at 1.3 yr) or 2 of 56 (4%) by the
received 74 transfusions (mean 2.8 episodes/patient; age of two years (unpublished data) compared with 23
range 1-9 episodes). Pre-transfusion Hb levels, available per cent by this age in Jamaica14. One Nagpur patient
in 57 episodes, varied from 1.6 to 8.2g/dl and were developed a stroke at 14 months compared with seven
below 6 g/dl in 38 (67%) (unpublished data). Red cell before the age of five years and an incidence of 7.8 per
indices were available in 35 patients in whom the pre- cent by 14 yr in the Jamaican cohort19. One Nagpur
transfusion MCH was below 26 pg in 23 (66%) and patient was deemed to have chronic hypersplenism
below 24 pg in 14 (40%) consistent with iron deficiency. which occurred in approximately five per cent of
Anaemia was more common during the six months of the Jamaican cohort (unpublished data). In Nagpur,
the monsoon period (June-November) accounting for osteomyelitis was diagnosed in two patients.
17 of 25 (68%) admissions. In the Jamaican cohort,
197 (63%) patients were given transfusions, the major Sepsis: Sepsis was clinically suspected in six patients
indications being parvovirus-induced aplastic crisis, but blood cultures performed in five showed no growth.
acute chest syndrome and acute splenic sequestration16. Sepsis might also have contributed to 38 episodes of
acute febrile illness, but of 28 blood cultures, only six
Splenomegaly: In Nagpur patients, splenomegaly yielded a potential pathogen (Staphylococcus aureus
occurred in 5 of 28 (15%) at six months, 12 of 40 coagulase negative 3, S. aureus coagulase positive
(30%) at one year and 11 of 29 (38%) at two years, 1, Klebsiella 1, diphtheroid 1). By contrast, severe
lower than the corresponding figures for Jamaica 37, infections in the Jamaican cohort were overwhelmingly
65 and 77 per cent17. Streptococcus pneumoniae, Haemophilus influenza B
and Salmonella spp.13,20-22.
Other clinical features: In Nagpur, dactylitis occurred
in seven (9%) patients before the age of five years Deaths: In the Nagpur cohort, 9 of 78 (12%) patients
(recurrent in 4) (unpublished data), compared to died (Table III), of whom three and possibly five deaths
frequencies of 8 per cent by six months, 24 per cent occurred in the first month of life so were probably
by one year and 45 per cent by two years in the unrelated to SS disease. Of the other deaths, few details
Jamaican cohort18. Acute chest syndrome occurred were available although one child was irritable and died
in nine, recurred in three and was usually associated on the way to hospital. In Jamaica, an early study of the
with admission. In Nagpur, acute splenic sequestration causes of death found that acute splenic sequestration
occurred in two patients (one with three events at 1.2, (ASS) accounted for 15, acute chest syndrome (ACS)
 330 INDIAN J MED RES, APRIL 2020

Table III. Details of deaths with presumed causes in Nagpur patients

Study Date of birth Date of death Age (yr) Clinical details Presumed causes
18 June 11, 2008 August 12, 2015 7.2 Severe anaemia Unknown
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+

34 January 1, 2010 January 5, 2010 *

Unknown Unknown Unknown ‑ no FU
Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

35 August 20, 2009 May 14, 2014 4.8 Unknown Severe anaemia with sepsis
49 June 6, 2010 June 21, 2012 2.1 Unknown Death on road, possible splenic
sequestration
60 August 7, 2010 November 2, 2010* Unknown Unknown Unknown
61 September 25, 2010 September 26, 2010 0.1 See presumed cause Meconium aspiration
75 July 30, 2010 September 20, 2011 1.1 Drowsy Unknown
90 June 3, 2011 June 23, 2011 0.1 See presumed cause Asphyxia, possible sepsis
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

94 June 29, 2011 July 7, 2011 0.1 Very low BW Unknown

*
Date last seen alive as date of death unknown. BW, birth weight; FU, follow up

for 13 and meningitis/septicaemia for eight of the 41 prophylaxis. Although there are no direct measures of
deaths before the age of two years23. Interpretation splenic function currently available in Indian patients,
of deaths become complicated by the changing the later appearance of splenomegaly is consistent with
management and interventions over long follow up, persisting function, which may explain why invasive
but it was clear that most mortality occurred within the pneumococcal disease has never been reported in
first three years of life, reduced with improving care, Indian SS disease.
and that acute chest syndrome was the dominant single
Dactylitis, which results from bone marrow
cause24.
necrosis, is a better indicator of pathology than bone
pain crisis which is influenced by many other factors,
Discussion
and the lower frequency of dactylitis in the Nagpur
First reported among tribal people in southern cohort was consistent with more mild disease. Severe
India25, there was an early misconception that the SS anaemia was a common cause of hospital admission,
gene was linked to the tribal origin, but it was found the lower MCH being consistent with iron-limited
to be widespread among the scheduled castes and erythropoiesis but reticulocyte counts, ferritin and
other backward classes in Odisha26 and only a small serum iron indices and a trial of iron supplementation
proportion was tribal in origin. The polymorphisms in may clarify the cause of anaemia. The lack of routine
DNA surrounding the beta-globin locus are different blood film examination for malarial parasites was a
from those observed in African peoples, most readily shortcoming of the present study especially in view of
explained as an independent occurrence of the HbS an increase during the monsoon period which might
gene, known as the Asian haplotype. This haplotype have been expected to be malaria-related. Jamaica
occurs in 91-100 per cent Indian patients with SS is malaria-free, but acute anaemia from parvovirus-
disease2,5,6,11 and is typical of the disease in the eastern induced aplasia with seroconversion in 70 per cent by
province of Saudi Arabia. the age of 20 yr32 would be missed in the absence of
reticulocyte counts.
The associated high HbF levels inhibit sickling
and promote the persistence of splenomegaly27. There were several limitations in comparing these
In African disease, there is a dichotomy between studies. Inevitably, the diagnostic technology for the
splenomegaly and splenic function whereby, despite newborn detection of SS disease has evolved, but
clinical enlargement, splenic function is often lost there has been ample confirmation of Hb genotype
early in life28,29 and early splenomegaly may predict during follow up. Recruitment of Nagpur patients
an increased susceptibility to infection17. The age was confined to the offspring of sickle-positive
specificity of invasive pneumococcal disease falls mothers, and although this would have missed cases
sharply after three years30, and the early loss of of S beta-thalassaemia and other double heterozygous
splenic function in patients of African origin results forms of SS disease, but would not bias the selection of
in an incidence of 10 per cent31 before pneumococcal cases with SS disease. Of a major concern was the high
 JAIN et al: SICKLE CELL DISEASE IN INDIA & JAMAICA 331

default rate in the Nagpur patients, noted in other Indian 5. Upadhye DS, Jain DL, Trivedi YL, Nadkarni AH, Ghosh K,
studies4; such default would have introduced bias, but Colah RB. Neonatal screening and the clinical outcome in
children with sickle cell disease in Central India. PLoS One
the nature of this bias could not be addressed as details 2016; 11 : e0147081.
were not available on the reasons for default. A further
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+

6. Jain D, Warthe V, Dayama P, Sarate D, Colah R, Mehta P,

deficiency was the limited information on the causes
Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

et al. Sickle cell disease in central India: A potentially severe

of death which, in Jamaica, were confirmed by formal syndrome. Indian J Pediatr 2016; 83 : 1071-6.
autopsies in over 50 per cent cases (unpublished data), 7. Jain DL, Sarathi V, Upadhye D, Gulhane R, Nadkarni AH,
but for cultural and other reasons were not confirmed Ghosh K, et al. Newborn screening shows a high incidence
in Indian patients although the young age in three and of sickle cell anemia in Central India. Hemoglobin
possibly five of nine deaths made it unlikely that these 2012; 36 : 316-22.
deaths were related to SS disease. 8. Serjeant GR, Serjeant BE, Forbes M, Hayes RJ, Higgs DR,
Lehmann H. Haemoglobin gene frequencies in the Jamaican
Both the studies had different durations of follow
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

population: A study in 100,000 newborns. Br J Haematol

up, but the observations were mostly confined to the 1986; 64 : 253-62.
first three years of life and this was unlikely to affect 9. Serjeant BE, Forbes M, Williams LL, Serjeant GR. Screening
the molecular features and the presented haematology cord bloods for detection of sickle cell disease in Jamaica.
Clin Chem 1974; 20 : 666-9.
and clinical features. Compared to Jamaicans, the
Nagpur patients demonstrated less alpha-thalassaemia, 10. Serjeant GR, Grandison Y, Lowrie Y, Mason K, Phillips J,
Serjeant BE, et al. The development of haematological changes
less dactylitis, a later appearance of splenomegaly, the in homozygous sickle cell disease: A cohort study from birth
apparent absence of pneumococcal septicaemia and a to 6 years. Br J Haematol 1981; 48 : 533-43.
high prevalence of unexplained severe anaemia. Cohort 11. Kulozik AE, Wainscoat JS, Serjeant GR, Kar BC,
studies from birth are vitally important in addressing Al-Awamy B, Essan GJ, et al. Geographical survey of beta
these questions, but mechanisms must be found to S-globin gene haplotypes: Evidence for an independent Asian
avoid the high default rates in this and other attempted origin of the sickle-cell mutation. Am J Hum Genet 1986; 39
: 239-44.
cohorts4. Furthermore, the lower prevalence of alpha-
thalassaemia in central India might have contributed to 12. Higgs DR, Pressley L, Serjeant GR, Clegg JB, Weatherall DJ.
The genetics and molecular basis of alpha thalassaemia in
the more severe disease compared to the milder disease association with Hb S in Jamaican Negroes. Br J Haematol
in other areas of India. 1981; 47 : 43-56.
Acknowledgment: Authors thank Dr Ian Hambleton of the Sir 13. John AB, Ramlal A, Jackson H, Maude GH, Sharma AW,
Serjeant GR. Prevention of pneumococcal infection in
George Alleyne Chronic Disease Research Centre, University of
children with homozygous sickle cell disease. Br Med J
the West Indies, Cave Hill, Barbados, for statistical assistance. (Clin Res Ed) 1984; 288 : 1567-70.
14. Emond AM, Collis R, Darvill D, Higgs DR, Maude GH,
Financial support & sponsorship: None. Serjeant GR. Acute splenic sequestration in homozygous
sickle cell disease: Natural history and management. J Pediatr
Conflicts of Interest: None. 1985; 107 : 201-6.
15. Mason KP, Grandison Y, Hayes RJ, Serjeant BE, Serjeant GR,
References Vaidya S, et al. Post-natal decline of fetal haemoglobin in
homozygous sickle cell disease: Relationship to parenteral Hb
1. Kar BC, Satapathy RK, Kulozik AE, Kulozik M, Sirr S, F levels. Br J Haematol 1982; 52 : 455-63.
Serjeant BE, et al. Sickle cell disease in Orissa State, India.
Lancet 1986; 2 : 1198-201. 16. Thame JR, Hambleton IR, Serjeant GR. Red cell transfusion
in homozygous sickle cell disease: Experience from the
2. Mukherjee MB, Lu CY, Ducrocq R, Gangakhedkar RR, Jamaican Cohort Study. Transfusion 2001; 41 : 596-601.
Colah RB, Kadam MD, et al. Effect of alpha-thalassemia
on sickle-cell anemia linked to the Arab-Indian haplotype in 17. Rogers DW, Vaidya S, Serjeant GR. Early splenomegaly in
India. Am J Hematol 1997; 55 : 104-9. homozygous sickle-cell disease: An indicator of susceptibility
to infection. Lancet 1978; 2 : 963-5.
3. Jain D, Italia K, Sarathi V, Ghosh K, Colah R. Sickle cell
anemia from Central India: A retrospective analysis. Indian 18. Stevens MCG, Padwick M, Serjeant GR. Observations on the
Pediatr 2012; 49 : 911-3. natural history of dactylitis in homozygous sickle cell disease.
Clin Pediatr (Phila) 1981; 20 : 311-7.
4. Italia Y, Krishnamurti L, Mehta V, Raicha B, Italia K,
Mehta P, et al. Feasibility of a newborn screening and 19. Balkaran B, Char G, Morris JS, Thomas PW, Serjeant BE,
follow-up programme for sickle cell disease among South Serjeant GR. Stroke in a cohort of patients with homozygous
Gujarat (India) tribal populations. J Med Screen 2015; 22 : 1-7. sickle cell disease. J Pediatr 1992; 120 : 360-6.
 332 INDIAN J MED RES, APRIL 2020

20. Rogers DW, Clarke JM, Cupidore L, Ramlal AM, Sparke BR, 26. Kar BC, Devi S. Clinical profile of sickle cell disease in
Serjeant GR. Early deaths in Jamaican children with sickle Orissa. Indian J Pediatr 1997; 64 : 73-7.
cell disease. Br Med J 1978; 1 : 1515-6. 27. Serjeant GR. Irreversibly sickled cells and splenomegaly in
21. Wright J, Thomas P, Serjeant GR. Septicemia caused by sickle-cell anaemia. Br J Haematol 1970; 19 : 635-41.
Sj32S5aMfaURMPpSpx6kqHsrJYCAzwc87vjF9AWfsygSxegOxz5e3FbD7ohHzTFC7/g1/iY6b1fgM1dwHV5bdUkgkLXb6GtqgJ2+

Salmonella infection: An overlooked complication of sickle 28. Pearson HA, Spencer RP, Cornelius EA. Functional asplenia
Downloaded from http://journals.lww.com/ijmr by HqANVXLJBTa/LZllVlNtExDcKk5+KxZ8e7ym37mFxA+WMXju5wmL

cell disease. J Pediatr 1997; 130 : 394-9. in sickle-cell anemia. N Engl J Med 1969; 281 : 923-6.
22. Knight-Madden J, Serjeant GR. Invasive pneumococcal 29. Pearson HA, McIntosh S, Ritchey AK, Lobel JS, Rooks Y,
disease in homozygous sickle cell disease: Jamaican Johnston D. Developmental aspects of splenic function in
experience 1973-1997. J Pediatr 2001; 138 : 65-70. sickle cell diseases. Blood 1979; 53 : 358-65.
23. Thomas AN, Pattison C, Serjeant GR. Causes of death 30. Wong WY, Powars DR, Chan L, Hiti A, Johnson C, Overturf G.
in sickle-cell disease in Jamaica. Br Med J (Clin Res Ed) Polysaccharide encapsulated bacterial infection in sickle cell
anemia: A thirty year epidemiologic experience. Am J Hematol
1982; 285 : 633-5.
1992; 39 : 176-82.
imK/icbKFBhW7RESQDs0pCkcFEkhaw== on 06/17/2024

24. Serjeant GR, Chin N, Asnani MR, Serjeant BE, Mason KP, 31. Lobel JS, Bove KE. Clinicopathologic characteristics
Hambleton IR, et al. Causes of death and early life determinants of septicemia in sickle cell disease. Am J Dis Child
of survival in homozygous sickle cell disease: The Jamaican 1982; 136 : 543-7.
cohort study from birth. PLoS One 2018; 13 : e0192710.
32. Serjeant BE, Hambleton IR, Kerr S, Kilty CG, Serjeant GR.
25. Lehmann H, Cutbush M. Sickle-cell trait in Southern India. Haematological response to parvovirus B19 infection in
Br Med J 1952; 1 : 404-5. homozygous sickle-cell disease. Lancet 2001; 358 : 1779-80.

For correspondence: Dr Graham Roger Serjeant, Sickle Cell Trust (Jamaica), 14 Milverton Crescent, Kingston 6, Jamaica
e-mail: [email protected]