ArticlePDF Available

Sickle cell disease in Sierra Leone: a neglected problem

Authors:

Abstract and Figures

Background: Sickle cell disease (SCD) is common in Sierra Leone although its exact prevalence, incidence and clinical spectrum are unknown.Methods: Using a statistical package, StatsDirect (Altrincham, United Kingdom) we analyzed the demographic characteristics, presentations, acute events, treatments and clinical outcomes in a cohort of SCD patients attending sickle cell clinics in Freetown, Sierra Leone between February 2007 and August 2010.Results: There were 446 patients, median age of 13 years. Of these, 435 were homozygotes (HbSS), median age 13 years also. There were 248 females, median age 12.5 and 198 males, median age 14, resulting in a male:female ratio of 0.79. Eleven (2.4%) were Sickle Cell-HbC disease, median age 14 years. Patients demonstrated many of the typical features of SCD. The most common reason for hospital admission was bone pain crisis associated with an infection, followed by severe anemia. Aseptic necrosis of the femoral head, leg ulcers, septic osteomyelitis and gallstones were seen in 0.22% of patients, but strokes and acute chest syndrome were not observed. The death rate was 2.51/100 patient years observation with an estimated mean survival of 3.6 years (CI 3.2-3.7). Severe anemia was implicated in the death of 8 patients (50%), whereas only 2 deaths (12.5%) were attributable to bone pain crisis. One death (6.25%) was associated with pregnancy complicated by severe anemia and another with an adverse blood transfusion event.Conclusion: The clinical outcomes in this series highlight the need for a more comprehensive provision of care for SCD patients in Sierra Leone.
Content may be subject to copyright.
December 2015 Volume 49, Number 4 GHANA MEDICAL JOURNAL
258
SICKLE CELL DISEASE IN SIERRA LEONE: A NEGLECTED PROB-
LEM
G. T. ROBERTS1, A. E. GABBA1, T. L. ROBERTS1, G. DEEN1,2 and I. WURIE3
1Sierra Leone Sickle Society, 25 Thomas Street, Freetown, Sierra Leone, 2Connaught Hospital, Freetown,
Sierra Leone, 3Ramsy Laboratory, 14 Liverpool Street, Freetown, Sierra Leone
DOI: http://dx.doi.org/10.4314/gmj.v49i4.7
Corresponding Author: George T. Roberts Email: gtr@sleonesickle.org
Conflict of Interest: None declared
SUMMARY
Background: Sickle cell disease (SCD) is common in
Sierra Leone although its exact prevalence, incidence
and clinical spectrum are unknown.
Methods: Using a statistical package, StatsDirect (Al-
trincham, United Kingdom) we analyzed the demo-
graphic characteristics, presentations, acute events,
treatments and clinical outcomes in a cohort of SCD
patients attending sickle cell clinics in Freetown, Sierra
Leone between February 2007 and August 2010.
Results: There were 446 patients, median age of 13
years. Of these, 435 were homozygotes (HbSS), medi-
an age 13 years also. There were 248 females, median
age 12.5 and 198 males, median age 14, resulting in a
male:female ratio of 0.79. Eleven (2.4%) were Sickle
Cell-HbC disease, median age 14 years. Patients
demonstrated many of the typical features of SCD. The
most common reason for hospital admission was bone
pain crisis associated with an infection, followed by
severe anemia. Aseptic necrosis of the femoral head,
leg ulcers, septic osteomyelitis and gallstones were
seen in 0.22% of patients, but strokes and acute chest
syndrome were not observed. The death rate was
2.51/100 patient years observation with an estimated
mean survival of 3.6 years (CI 3.2-3.7). Severe anemia
was implicated in the death of 8 patients (50%), where-
as only 2 deaths (12.5%) were attributable to bone pain
crisis. One death (6.25%) was associated with pregnan-
cy complicated by severe anemia and another with an
adverse blood transfusion event.
Conclusion: The clinical outcomes in this series high-
light the need for a more comprehensive provision of
care for SCD patients in Sierra Leone.
Keywords: Sickle cell disease, Sierra Leone, survival,
anaemia, haemoglobinopathy
INTRODUCTION
One hundred years ago, Dr J.B. Herrick, a physician
practicing in the American city of Chicago, published
the first description of sickle cell disease (SCD) in the
western medical literature.1 His patient, Walter Clem-
ent Noel, a native of the West Indian Island of Grenada
had been a student at the city’s College of Dental Sur-
gery between the years 1904 and 1907. In the century
since that first report, a considerable body of
knowledge has been amassed on the biology, epidemi-
ology, management and treatment of SCD throughout
many regions of the world. However, even though Si-
erra Leone lies within the equatorial belt in Africa,
where the highest estimates of the sickle gene have
been recorded, 2 very little information on the disease
has been published from the country. The only signifi-
cant work in the century since Herrick’s first report
was that of Knox-Macaulay who, in 1983, published
his observations on a series of 121 Sierra Leonean pa-
tients whom he had been following prospectively.3
One hundred and six of Knox-Macaulay’s patients
were homozygous SCD (HbSS) with a small minority
of 15 (12.4%) sickle cell/hemoglobin C or HbSC dis-
ease. Interestingly, Knox-Macaulay observed that 55%
of his patients were descendants of African slaves who
had regained their freedom and had been repatriated
from North America and the West Indies, as well as
others directly from other countries in Western Africa
who had been liberated from ships that were taking
them across the Atlantic Ocean to slavery.4 These freed
slaves were all landed at the port of Freetown, now the
capital city of Sierra Leone. It goes without saying,
therefore, that the descendants of those freed slaves,
who are now called “Creoles,” but more correctly,
“Krios,”5 have strong ethnic and genetic relationships
with Black West Indians and African-Americans, clos-
ing the circle back to that foundation paper by Dr Her-
rick.
December 2015 G. T. Roberts et al Sickle Cell Disease Neglected in Sierra Leone
259
Ethnic diversity is of course an important factor in un-
derstanding some of the clinical aspects of SCD be-
cause haplotype diversity, occurring among ethnic
groups can distinguish one community of sickle gene
carriers from another .6 By the same token, this type of
diversity can mediate clinical manifestations of the
disease, for better or for worse.7 Notwithstanding this,
however, it was not surprising that Knox-Macaulay
was unable to detect any significant clinical differences
between Sierra Leonean “Creoles” and “non-Creoles.”
It is not surprising because of a number of reasons.
Firstly, the numbers were too small for statistical pow-
er to accrue in the cohort. Secondly, the Creole ethnic
group is extremely diverse in its African, Afro-
American and Afro-Caribbean origins as we have al-
ready seen.5 Slaves, landed in the West Indies and
America came from a variety of African sources.8
Some of those who were taken to America, in particu-
lar, came originally from the Sierra Leone hinterland.9
Those who had come from elsewhere would have, in-
evitably, during the hundred or so years before eventu-
al repatriation to Sierra Leone, inter-married, not only
among themselves, but probably also with slaves who
had been taken directly from Sierra Leone. Further
diversity in the Creole group would have occurred, as
explained previously, as a result of individuals intro-
duced into the early community directly from various
West African sources (including Sierra Leone) during
the early to mid-nineteenth century.9 This latter group
of “liberated Africans” as they were called, eventually
integrated and intermarried with the returnees from
across the Atlantic Ocean, and indeed other Sierra Le-
oneans.9
When Knox-Macaulay compared Sierra Leone sickle
cell patients with other groups of sickle cell patients
elsewhere in the world, both similarities and diver-
gences were observed. For example, vaso-occlusive
events were similar to those in American, Jamaican,
Ghanaian and Nigerian patients. 10,11 And whereas the
frequency of leg ulceration in Sierra Leonean sickle
cell patients was relatively low (13.2% SS, 13.3% SC)
when compared to patients in the United States (73.6%
SS) and Jamaica (63.3% SS), it was relatively high in
comparison to Nigerian and Ghanaian patients.
On the other hand, avascular necrosis of the femoral
head (ANFH) was more common among Sierra Leone-
an patients as a whole (8.5% SS, 20% SC) than in
Ghanaians (2.8% SS, 6.6% SC), although similar to
frequencies in Jamaican patients (8.2% SS, 18% SC).
Although Knox-Macaulay considered that these differ-
ences in complication rates could probably be attribut-
ed to environmental factors, they are only likely to be
fully understood if haplotype and other biological ele-
ments are factored in.
As far as environmental factors go, they not only influ-
ence clinical outcomes but, at least one, malaria, in
addition to potentially provoking acute painful epi-
sodes in the sickle cell patient, underpins the high
prevalence rates the sickle gene demonstrates wherever
it occurs.12 Half a century after Herrick’s report, it was
hypothesized that the high prevalence of beta-
thalassemia trait was the result of a balance between
the red cell abnormality and Plasmodium falciparum
malaria.13 This hypothesis was subsequently extended
to include other red blood cell polymorphisms among
which, HbS is preeminent.14
The protection against severe malaria that the sickle
trait (AS) and other mild RBC abnormalities afford
provides a survival advantage for individuals who carry
them.15 Consequently, the hypothesis goes, individuals
who carry the traits enjoy a relatively robust resistance
to malaria and survive to adulthood, whilst homozy-
gotes, on the other hand, die early, succumbing to a
variety of environmental challenges.16 In Sierra Leone,
where P. falciparum malaria is hyperendemic, 17 it can
be expected, therefore, that the prevalence of the sickle
gene would be high.
Two reports, one in the mid-fifties and the other, four
decades later, examined the prevalence of the trait
among blood samples in two separate series. In the
earlier report, Rose and Suliman examined the preva-
lence of sickle cell trait (SCT) among individuals of the
Mende ethnic group, 18whilst in the later publication
Wurie et al reported a sickle cell positive rate of 22%
among 3274 sodium metabisulfite-tested specimens
processed in their laboratory during the early 1990’s.19
Although these reports are useful, they do not, howev-
er, address some of the important questions about prev-
alence among communities in Sierra Leone. Nor do
they begin to tackle the magnitude of the SCD burden
and its consequences among Sierra Leoneans. Moreo-
ver, the only report focusing on clinical features was
published in 1983.3 The rationale for undertaking this
study, therefore, is to update information about the
disease in Sierra Leone and to re-evaluate its clinical
features in patients in this country. Furthermore, a
study such as this could provide a basis for greater in-
sight into the factors that influence clinical outcomes.
December 2015 Volume 49, Number 4 GHANA MEDICAL JOURNAL
260
METHODS
The patients
The patients in this study were registered at the clinics
of the Sierra Leone Sickle Cell Society (SLSCS) in
Freetown, from 1st February, 2007 to 31st August 2010.
Patients consisted predominantly of children under the
age of 18 years. At the clinics, they received intensive
counselling about the nature of SCD and its complica-
tions and how to prevent and manage crises. In addi-
tion, they were given basic medications to assist nutri-
tion (folic acid) and prevent complications (Penicillin
V, Amoxicillin). Anti-malaria prophylaxis is provided
with weekly Pyrimethamine supplemented with advice
to sleep inside an insecticide-treated bed net. Painful
crises, when mild, were managed at home and at the
clinics with mild analgesics including Paracetamol,
Ibuprofen and Diclofenac plus oral rehydration solu-
tions.
Patients with complicated and more severe pain, not
controlled by these measures, were referred on to hos-
pital for more intensive care. Other symptoms that
could not be managed at the clinics were also referred
to hospital. Patients were followed up on regular
monthly visits, and non-attendance at specified ap-
pointments was investigated by mobile telephone and,
where feasible, home visits to patients who continue
not to show up.
Procedures
We retrieved the records of patients in the clinics of the
SLSCS and extracted the demographic data of date of
registration, age first seen at the clinics, gender, clinical
features and date of death and age at death. The data on
hemoglobin phenotype, determined by alkaline elec-
trophoresis on cellulose acetate medium was also ex-
tracted. Data of ethnic group, as reported by the patient
or parent, was also obtained. Records of landmark clin-
ical events as well as reasons for onward referral were
also retrieved. Causes of death were evaluated from
clinical observations in the terminal events that preced-
ed death.
Statistical analysis
Retrieved data was analyzed using the statistical pack-
age Stats Direct (Altrincham, United Kingdom, WA14
4QA) that provided descriptive characteristics as well
as survival analysis. ANOVA was used to compare
ages of the various categories of patients and survival
characteristics were estimated by the Kaplan-Meier
method. Start date of analysis was taken as the date at
which the patient was registered. All surviving patients
were censored at the same date, 31 August 2010.
RESULTS
There were 446 patients, representing 637 patient-
years. The median age of the entire cohort was 14
years. The demographic data of age, gender and ethnic
distributions are shown in Tables 1-3 and in Figure 1.
!
Figure 1 Age structure of Sickle Cell Disease Patients
in Sierra Leone
Table 1 Sex and Age distribution of Sickle Cell Dis-
ease Patients
Phenotype
Number
Percent
Median Age (years)
All SCD Patients
446
14
All SCD Females
248
55.6
13
All SCD Males
198
44.4
14
Table 2 Sex and age distribution of HbSS and HbSC
Patients
Percent
Median Age (years)
SS only
97.5
13
Female
55.2
12.5
Male
44.8
14
HbSC
2.5
14
Female
63.6
-
Male
33.4
-
Table 3 Distribution by Tribe compared with Census
Distribution
Ethnic Group
Percentage
Census Percentages
TEMNE
30
30
MENDE
15
30
KRIO
13
10
OTHERS
12
30
Homozygous sickle cell disease (HbSS) constituted the
vast majority of patients, accounting for 435 (97.5%),
whilst HbSC disease, the only other phenotype detect-
ed consisted of only 11 patients. ANOVA was used to
compare the ages among all patient categories but no
significant differences were revealed. Also, we could
not detect any differences in ethnic distribution be-
tween HbSS and HbSC patients.
Clinical features
Clinical features encompassed some of the typical
complications of SCD, with painful crises being the
most frequent departures from the steady state. For the
twelve month period when adequate figures were
available, 48 (10.8%) patients required hospital admis-
December 2015 G. T. Roberts et al Sickle Cell Disease Neglected in Sierra Leone
261
sion. Of these, 16 were children under 10 years of age.
Most admissions were for painful crises, associated
with an infection episode.
Causes of the infection were not determined although
some were attributed to malaria. However, 13 patients
were admitted because of severe anemia. Three pa-
tients underwent surgical procedures, of which 2 were
Caesarean sections. The third was for drainage of sep-
tic osteomyelitis. The organism involved was not de-
termined. Thirteen patients received non-elective in-
patient blood transfusion. One case each, of ANFH and
leg ulcers, were observed.
There were no cases of stroke in the series, although 1
patient (0.22%) had neuropsychiatric disorder that im-
paired his societal interactions. One patient (0.22%)
reported gallstones which she passed per rectum and an
adolescent male reported priapism. Three pregnancies
were recorded, one of which resulted in maternal and
foetal death (33.3% mortality).
Survival
The majority of patients continue to live relatively ac-
tive lives, attending school and, for adults, holding
down jobs. However, a total of 16 (3.6%) patients have
died, all with HbSS phenotype. The age at death ranged
from 7-27 years, with a median of 17 years. Using the
date of first registration as base, an attempt was made
to calculate survival by Kaplan-Meier analysis (Figure
2), but the median survival (ordinate, in days) was too
extended to be determinable. The mean incidence of
death, however, was 2.51 per 100 patient-years. Esti-
mated mean survival was 3.6 years (95% CI, 3.2 3.7
years).
!
Figure 2 Survivals in 446 Sickle Cell Disease Patients
Causes of Death
The causes of death were not easy to determine. There
were no autopsies. However, based on clinical events
immediately preceding the deaths, causes of death were
assigned, as indicated in Table 4 in which patients are
identified by their unique patient numbers*. Signifi-
cantly, 8 patients (50%) died of complications associ-
ated with severe anaemia and one patient (6.25%) had
an adverse transfusion incident consistent with over-
transfusion and/or haemolytic reaction during treatment
for severe anaemia, and another patient died with
anaemia complications associated with pregnancy.
Table 4 Causes of Death
Patients*
Age
Sex
Survival
Cause of Death
185
18
F
398
Severe anaemia
97
7
M
361
Unknown
254
3
M
493
Unknown
37
12
F
1064
Unknown
84
16
M
351
Severe anaemia
42
19
F
616
Bone pain crisis
175
11
M
595
Severe anaemia
85
7
M
569
Unknown
142
26
M
326
Bone pain crisis
199
9
M
342
Unknown
64
6
F
817
Severe anaemia
87
10
M
161
Severe anaemia
48
19
M
1029
Unknown
41
20
F
449
Pregnancy & anaemia
144
19
F
623
Severe anaemia
7
27
F
1141
Transfusion incident
DISCUSSION
The prevalence and incidence of SCD in Sierra Leone
is unknown. However, based on limited survey results,
the frequency of the trait is probably in the region of
about 20-25%, 18,19 which would result in approximate-
ly 10-16 SS cases per 1000 live births annually. Using
this figure and an estimated population of 6.4 million,
20 and with an annual birth rate of 44.7/1000, 20 it is
likely that between 2816 and 4400 HbSS babies are
born every year. To this should be added babies that
are compound heterozygotes, the incidence of which is
entirely unknown. However, their number is not likely
to be less than 344 and could exceed 546, using data
from Knox-Macaulay.3
Thus, the total number of new additions of sickle cell
haemoglobinopathy to the population could be in the
region of 3160 to 4946 annually. Determination of how
many of these newborns survive to beyond 5 years
could be fraught with difficulty as has been noted
elsewhere.21 However, subtracting the under-fives in-
fant mortality of 154/1000 live births reported for Sier-
ra Leone, 20 will result in a survival of between 3006
and 4792 babies. These numbers will add to their pre-
decessors already surviving in the population. Deter-
mination of this cumulative number is, again, difficult21
and only a well-structured population survey can eluci-
date it.
However, it can be assumed that this number is proba-
bly in the tens of thousands per generation, even if sub-
sequent cumulative mortality is huge.
December 2015 Volume 49, Number 4 GHANA MEDICAL JOURNAL
262
The patients we present in the current study, therefore,
are likely to represent only a tiny fraction of SCD pa-
tients in the country. With that caveat, the cohort illus-
trates a number of features. Firstly, it confirms that
HbSS disease predominates, although in this series, the
proportion of the only other phenotype, HbSC, was, at
2.5%, smaller even than the 12.4% that Knox-
Macaulay had observed in 1983.3 Then, as in the cur-
rent series, no other phenotypes were observed.
The reason for this is not known, but, in our view, is
likely to be due to technical factors because, the only
procedure applied for diagnosis is cellulose acetate
electrophoresis, in which other variants could be
missed. There is anecdotal evidence, however, of the
presence of compound heterozygotes for beta-
thalassemia (HbS Beta-thalassemia) in at least 2 unre-
lated Sierra Leonean families, diagnosed elsewhere.
Furthermore beta-thalassemia trait frequencies of 9%
have been reported from Liberia, with which Sierra
Leone shares its eastern border.21
Another possible reason that could account for the ap-
parent paucity of phenotypes other than HbSS is that
other phenotypes may be milder than HbSS and there-
fore, do not seek medical attention or may get their
treatment and management advice from traditional
providers. The age structure of the cohort (Figure 1) is
interesting in that median age is only 14 years, com-
pared to 17 for the population at large.20 This finding
suggests that survival beyond childhood may be rela-
tively reduced among SCD patients, as has been well-
recognized elsewhere.23
This interpretation is reinforced by the fact that under
14’s represent more than 59% of the group, in contrast
to only 44.5% in the general population.20 However,
these observations should be interpreted with caution,
as it is possible that older patients do not present them-
selves for a variety of reasons, one of which is that
older, surviving patients may have milder disease and
so do not seek medical attention.
The ratio of male to female is massively against males
(198:248, or 0.79). In the general population this ratio
is about 0.9 in the age sector under consideration.20 The
cause for this disparity is unknown. When Knox-
Macaulay published his series in 1983, he observed
that the Krios predominated over the other ethnic
groups.3The proportions are reversed in the current
series (Table 3), consistent with a demographic shift in
this part of the country. In any case, the country-wide
distribution of ethnic groups currently stands at, Temne
30%, Mende 30%, Krio 10% and other 30%.20 Our
series reflects these current trends, certainly with re-
spect to Temnes and Krios. On the other hand, the situ-
ation in other parts of the country, where ethnic distri-
bution may be more homogenous, is unknown. This is
an important point to unravel, because provision of
sickle cell care services in the future would depend
partly on disease prevalence within communities.20
Clinical manifestation of SCD in the current series in-
dicates that some features are not as severe or frequent
as reported from other countries and indeed, in Knox-
Macaulay’s series. For example, ANFH was seen in
only one patient (0.22%), contrasting with a 2.9% inci-
dence reported from elsewhere in Africa.24 However,
apart from symptoms or physical signs, no systematic
imaging techniques were used to assess the presence of
hip joint disease. It would be important to ascertain the
rarity of ANFH in this and similar groups of patients
and to determine what underlies it.
Leg ulcers were also uncommon among our patients.
Only one patient, a 19 year-old HbSS male had this
complication, equivalent to a rate of only 0.16 per 100
patient years of observation, unlike elsewhere in Afri-
ca.25 Here again, the reason for this rarity is unclear.
Gallstones, detected by imaging techniques, have
shown, depending on age, prevalences as high as 58%
in series from Jamaica, for example,26 although they
appear less frequent in African series.27 In ours, where
imaging techniques were not used, we observed only 1
case, in a 25 year old female, who passed the stone per
rectum, without symptoms. Clearly, this is an area that
needs further investigation.
The reasons why patients were admitted to hospital
varied, but the most common was for pain crisis asso-
ciated with a febrile episode. Although some of these
patients reportedly had malaria, the causes for fever in
others were not determined. Neither was the causative
organism identified in the single patient with septic
osteomyelitis. Bacteriological cultures were not availa-
ble. Lack of microbiological detail is a major defect in
our programme, since infection is a recognized risk
factor for morbidity and mortality in SCD. For exam-
ple, malaria was a principal cause for morbidity in
Kenyan SCD patients.28 On the other hand, the organ-
isms involved in bacterial sepsis remain a cause for
debate probably because of the lack of adequate identi-
fication procedures.29 This is another area of research
that requires attention.
In Nigeria, neurological incidents have been reported
in varying frequencies among patients with SCD. For
example, Fatunde et al, in Ibadan, found that, over a 15
year period, 5.4% of under-6 year-olds attending a
December 2015 G. T. Roberts et al Sickle Cell Disease Neglected in Sierra Leone
263
sickle cell clinic developed strokes.30 Therefore, the
absence of overt stroke in our series is surprising alt-
hough a single case of neuropsychiatric disorder was
observed in our patient with bilateral ANFH. It may be
that stroke-affected patients are seen at stroke clinics
elsewhere, where they receive treatment and follow-up.
But an alternative reason might be that SCD patients
with stroke may have had severe disease to which they
had succumbed before having an opportunity to present
at out clinics. No systematic study of potential neuro-
logical impairment either by Doppler and/or by formal
neuropsychiatric testing has been undertaken, nor were
we able to conduct imaging studies such as CTI or
MRI that could have revealed asymptomatic neurologi-
cal lesions.
Some patients presenting with severe anemia required
emergency blood transfusion usually attended by crises
in blood procurement. When such crises were resolved,
the clinical outcome was mainly satisfactory. However,
in other instances, lack of appropriate blood apparently
contributed to a fatal outcome. In one case, in contrast,
a serious transfusion reaction was apparently a contrib-
utory factor to a fatal outcome in a 27 year-old female.
Sickle cell disease is a well-recognized risk-factor for
poor outcomes in pregnancy.31 In our series, three
pregnancies occurred, resulting in good outcomes for
both mother and child in two. However, in a third case,
both mother and baby died during a Cesarean section in
the severely anemic mother. Although this series of 3 is
meager, a 33% mortality deserves close scrutiny to
ensure better outcomes.
Priapism, another potential cause that could impair
reproductive competence, was rare in this series, rec-
orded in only 0.5% of males, a remarkably low inci-
dence when compared to other series. An international
study of priapism in SCD demonstrated a prevalence of
35% among males aged 4-66 years, with the earliest
manifestation reported at age 12 years.32 Of 46 patients
reporting priapism, 21% reported having erectile dys-
function. Why our series contained only one case is
unclear, even though 62.5% of cases were 12 years and
older. However, reluctance to report the symptom be-
cause of embarrassment could be a factor. A more rig-
orous attempt to determine the extent of priapism needs
to be made in order to minimize improper management
that could contribute to subsequent erectile dysfunc-
tion.
Determining the cause of death in the 16 deaths has
been difficult, principally because of the lack of autop-
sies. Nevertheless, using clinical information immedi-
ately before death, provisional causes could be as-
signed, bearing in mind, however, that autopsies re-
main the gold-standard for determining cause of death,
especially in clinical studies. Nonetheless, with this
proviso, the most frequent cause of death was “severe
anemia,” accounting for or involved in 8 (50%) of the
deaths, one of which was associated with pregnancy
and delivery.
The next most frequent cause of death was “bone pain
crisis,” which was recorded for 2 patients. A transfu-
sion reaction that occurred during the transfusion of a
second unit of blood after the uneventful transfusion of
a prior unit for severe anemia was implicated in the
death of one patient.
The Kaplan-Meier 50% survival estimate, taken from
the date of registration, could not be determined as it
was too extended (Figure 2). The incidence of death,
however, stands at 2.51 per 100 patient years. The ob-
servation period, at 637 patient-years is relatively short,
but even so, this death incidence is extremely high
when compared to other countries.23 If this alarming
figure is confirmed, it would constitute a call for urgent
action. Similarly, the mean survival time, estimated at
slightly more than 3½ years emphasises the dire out-
look for SCD patients in this country.
Many implications arise from this study. Firstly, the
patients studied constitute a very narrow spectrum of
SCD patients in the country. To know more about the
nature of SCD in Sierra Leone, studies like the present
one need to be repeated or expanded. Another im-
portant consideration is that our patients are young
with relatively few adults in the cohort, which could be
interpreted in a number of ways, including that SCD
patients do not survive beyond early adulthood. Alt-
hough there might be an element of self-exclusion
among the older patient, extremely high death inci-
dence in the cohort is consistent with a high rate of loss
among SCD patients of all ages.
Whatever the case, a formal examination needs to be
carried out to obtain more reliable survival data. In
addition, there is a need for better information about
the clinical features of SCD and, especially, the risk
factors for hospital admission and for death.
Malaria has been implicated as a risk factor elsewhere
on the continent,28 and there is, currently, debate about
the role of bacterial infections, especially Streptococ-
cus pneumoniae, in morbidity and mortality in African
SCD.29 Risk factors and causes of death in SCD are not
December 2015 Volume 49, Number 4 GHANA MEDICAL JOURNAL
264
known for this country in contrast to other African
countries,33 so an improved method of death reporting
up to and including autopsies is mandatory.
That 50% of the deaths were attributable to anaemia,
not treated with blood transfusion, signifies that access
to blood transfusion services require upgrading. Simi-
larly, improved microbiological services are required to
manage febrile illnesses appropriately and help in de-
fining preventive measures such as immunizations and
chemoprophylaxis. It is of interest that the rates of
complications seen in this study are much less than
those observed when Knox-Macaulay studied SCD
patients in the Freetown community thirty years ago.
Why there are these differences is unknown, but since
1983 there have been significant population shifts be-
cause of civil instability in spite of which, however,
some beneficial changes in social amenities have oc-
curred. It is certainly relevant that patients followed in
a clinic setting, where advice about sickle cell coping
strategies is given, does have a beneficial effect on
clinical outcomes.34
Finally, there is no data relating to ethnic or regional
patterns of SCD in the country, although it is likely that
differences will be trivial. In any event, it would be
important to establish gene frequencies and disease
burden in the various districts in order to set priorities
for service provision.
CONCLUSION
Although the challenges seem daunting, the best way to
answer the questions this study has raised would be in
a new-born screening study protocol in which all or the
majority of new-borns with SCD in an area or district
are identified and subsequently followed systematically
and cared for in a structured way. Given the findings in
our study, instituting such a protocol should be consid-
ered urgent.
REFERENCES
1. Herrick JB Peculiar, elongated and sickle-shaped
red blood corpuscles in a case of severe anemia.
Arch. Intern. Med 1910; 6:517521.
2. Modell B, Darlison M. Global epidemiology of
haemoglobin disorders and derived service indica-
tors. Bull. World Health Organ. 2008; 86:4807.
3. Knox-Macaulay HH Sickle cell disease in Sierra
Leone: A clinical and haematological analysis in
older children and adults. Ann Trop Med Parasitol.
1983; 77: 411-9.
4. Fyfe C. A History of Sierra Leone. (Oxford Uni-
versity Press 1962)
5. Wyse AJG. The Krios of Sierra Leone: an inter-
pretive study (C. Hurst, London, 1989).
6. Pagnier J, Mears JG, Dunda-Belkhodja O,
Schaefer-Rego KE, Beldjord C, Nagel RL Labie
D. Evidence for the multicentric origin of the sick-
le cell hemoglobin gene in Africa. Proc Natl Acad
Sci U S A. 1984; 81:1771-3.
7. Powars D, Hiti A. Sickle cell anemia. Beta s gene
cluster haplotypes as genetic markers for severe
disease expression. Am J Dis Child. 1993;
147:1197-202.
8. Curtin P. The Atlantic Slave Trade: A Census.
University of Wisconsin 1969
9. Wyse AJG. Searchlight on the Krios of Sierra Le-
one: An ethnographical study of a West African
people. Occasional paper. Institute of African
Studies, Fourah Bay College, 1980.
10. Konotey-Ahulu, F.I.D. The Sickle Cell Diseases:
clinical manifestations including the ‘sickle crisis’.
Arch Int Med. 1974: 133: 611-619.
11. Hendrickse R.G. Sickle cell anaemia in Nigerian
children. Cent Afr J Med. 1960; 6: 45-57.
12. Haldane, J. B. S. The rate of mutation of human
genes. In: Proceedings of the Eighth International
Congress of Genetics. Hereditas. 1949; 35:267
73.
13. Allison, A. C. Polymorphism and natural selection
in human populations. Cold Spring Harb. Symp.
Quant. Biol. 1964; 29: 137149.
14. Siniscalco M. et al. Population genetics of haemo-
globin variants, thalassaemia and glucose-6-
phosphate dehydrogenase deficiency, with particu-
lar reference to the malaria hypothesis. Bull. World
Health Organ. 1966; 34: 37993.
15. Piel FB, Patil AP, Howes RE. Global distribution
of the sickle cell gene and geographical confirma-
tion of the malaria hypothesis. Nature Communi-
cations 2010;| 1:104 | DOI: 10.1038/ncomms1104
|www.nature.com/naturecommunications
16. Allison, A. C. Protection afforded by sickle-cell
trait against subtertian malarial infection. BMJ
1954; 1: 290294.
17. Barnish G, Maude GH, Bockarie MJ, Erunkulu
OA, Dumbuya MS, Greenwood BM Malaria in a
rural area of Sierra Leone. II. Parasitological and
related results from pre- and postrains clinical sur-
veys. Ann Trop Med Parasitol. 1993; 87: 137148.
18. Rose JK, Suliman JD. Sickle Cell trait among the
Mende ethnic group of Sierra Leone. West Afr
Med J. 1955; 45:
19. Wurie AT, Wurie IM, Gevao SM, Robbin-Coker
DJ. The prevalence of sickle trait in Sierra Leone:
A Laboratory profile. West Afr J Med. 1996;
15:201-3.
December 2015 G. T. Roberts et al Sickle Cell Disease Neglected in Sierra Leone
265
20. 2009 World Fact Book. United States Central In-
telligence Agency (2009)
21. Hassell KL. Population Estimates of Sickle Cell
Disease in the U.S. Am J Prev Med. 2010;38:512
21
22. Willcox MC. Thalassaemia in northern Liberia. A
survey in the Mount Nimba area. J Med Genet.
1975; 12:55-63.
23. Quinn CT, Rogers ZR, Buchanan GR. Survival of
children with sickle cell disease. Blood
2004;103:4023-27.
24. Ndugwa CM. Aseptic necrosis of the head of the
femur among sickle cell anaemia patients in
Uganda. East Afr Med J. 1992; 69:572-6.
25. Yetunde A, Anyaegbu CC. Profile of the Nigerian
sickle cell anaemia patients above 30 years of age.
Cent Afr J Med. 2001; 47:108-11.
26. Webb DKH, Darby JS, Dunn TDT, Terry SI, Ser-
jeant GR. Gall stones in Jamaican children with
homozygous sickle cell disease. Arch Dis Child.
1989; 64: 693-696
27. Longo-Mbenza B, Ngiyulu R, Kizunda P, Kaluila
M, Bikangi N. Gallbladder disease in young Con-
golese with sickle cell anemia: an ultrasound sur-
vey. J Trop Pediatr. 2004; 50:73-7.
28. Makani J, Komba AN, Cox SE et al. Malaria in
patients with sickle cell anemia: burden, risk fac-
tors, and outcome at the outpatient clinic and dur-
ing hospitalization. Blood 2010; 115:215-220.
29. Obaro S. Pneumococcal infections and sickle cell
disease in Africa: does absence of evidence imply
evidence of absence? Arch Dis Child. 2009;
94:713-6.
30. Fatunde OJ, Adamson FG, Ogunseyinde O, So-
deinde O, Familusi JB. Stroke in Nigerian children
with sickle cell disease. Afr J Med Med Sci. 2005;
34:157-60.
31. Omo-Aghoja IO, Okonofua FE. Pregnancy out-
come in women with sickle cell - a five year re-
view. Niger Postgrad Med J. 2007; 14: 151-4.
32. Adeyoju AB, Olujohungbe AB, Morris J, Yar-
dumian A, Bareford D, Akenova A, Akinyanju O,
Cinkotai K, O'Reilly PH. Priapism in sickle-cell
disease; incidence, risk factors and complications -
an international multicentre study. BJU Int. 2002;
90: 898-902.
33. Van-Dunem JC, Alves JG, Bernardino L, Figuei-
roa JN, Braga C, do Nascimento Mde L, da Silva
SJ. Factors associated with sickle cell disease mor-
tality among hospitalized Angolan children and
adolescents. West Afr J Med. 2007 Oct-Dec;
26:269-73.
34. Rahimy MC, Gangbo A, Ahouignan G, Adjou R,
Deguenon C, Goussanou S, Alihonou E. Effect of
a comprehensive clinical care program on disease
course in severely ill children with sickle cell
anemia in a sub-Saharan African setting. Blood
2003; 102:834-8
... The NGO was also supported by Sierra Leoneans working in the diaspora who brought with them the latest scientific knowledge, medical language and resources. They supported prioritisation of SCD as neglected public health issue (Ware, 2013) with a strong focus on understanding prevalence, improving medical care and ensuring prevention (Roberts et al., 2015). Our work was not regarded as particularly important by medical professionals, politicians nor policy makers, although they were supportive. ...
... There are several variants of SCD with the most common being termed HbSS and the milder version HbSC (Weatherall, 2010). Sierra Leone is affected by SCD, with an estimated 3000 infants born each year, that is, approximately 1.3% of all new-borns in Sierra Leone (Roberts et al., 2015). Other estimates state that 19 in 1000 births will have a major haemoglobinopathy (WHO, 2019) and that around a fourth of the population carries a variant of the sickle cell gene but this differs by ethnic group (Knox-Macaulay, 1983), and there are reported differences between rural and urban settings (Roberts et al., 2015). ...
... Sierra Leone is affected by SCD, with an estimated 3000 infants born each year, that is, approximately 1.3% of all new-borns in Sierra Leone (Roberts et al., 2015). Other estimates state that 19 in 1000 births will have a major haemoglobinopathy (WHO, 2019) and that around a fourth of the population carries a variant of the sickle cell gene but this differs by ethnic group (Knox-Macaulay, 1983), and there are reported differences between rural and urban settings (Roberts et al., 2015). In a 2013 survey to comprehend high levels of anaemia, conducted prior to the Ebola outbreak, Wirth et al. (2018) noted a combined prevalence for sickle cell trait and SCD in children of 21%. ...
Article
Most research on sickle cell disorders has tended to be gender-blind. This qualitative study undertaken in 2018, explores if and how sickle cell disorders become gendered in Sierra Leone through the analytical framework of a feminist ethics of care. It argues that women have to navigate moral blame when they have children with the condition. At the same time women refashion moral boundaries so that gendered norms around childhood and parenting for such children become suspended, in favour of creation of careful spaces. Parental fears of physical and sexual violence mean that gendered sexual norms are enforced for teenage boys as they are encouraged into early adulthood. In contrast, girls are kept in enforced ignorance about the consequences of sickle cell for reproduction and are encouraged to delay motherhood. This is because, as women relate, relationships and giving birth are fraught with embodied dangers and risks of violence.
... Sierra Leone is one of the countries in West Africa most affected by SCD. Estimates have fluctuated from 19 out of 1,000 births affected (WHO, 2017) to 3,000 infants with SCD being born each year, that is, approximately 1.3% of all new-borns in Sierra Leone (Roberts et al., 2015). It is estimated that around one in four people carries a variant of the sickle cell trait (Wurie et al., 1995), but that this differs by ethnic group (Livingstone, 1958;Knox-Macaulay, 1983) and there are differences between rural and urban settings (Roberts et al., 2015). ...
... Estimates have fluctuated from 19 out of 1,000 births affected (WHO, 2017) to 3,000 infants with SCD being born each year, that is, approximately 1.3% of all new-borns in Sierra Leone (Roberts et al., 2015). It is estimated that around one in four people carries a variant of the sickle cell trait (Wurie et al., 1995), but that this differs by ethnic group (Livingstone, 1958;Knox-Macaulay, 1983) and there are differences between rural and urban settings (Roberts et al., 2015). The last prevalence study dates from the 1990s and indicates that different variants of SCD exist in the population (Wurie et al., 1995) but we do not know at what levels (Wirth et al., 2018). ...
... Recent small sample studies investigating anaemia in the population have found a prevalence in children of both sickle cell and trait of 21% but this decreased by half when examining women (Wirth et al., 2018). If one out of four people are carrying the gene, a figure of 25% would be representative (Roberts et al., 2015) but indicates that children with SCD are dying before they reach adulthood. In Liberia, a small-scale pilot of screening in a hospital setting found SCD in 1.5% of infants (Tubman et al., 2016). ...
Technical Report
Full-text available
Sierra Leone is thought to be one of the West African countries most affected by sickle cell disorders. Estimates state that one in four people carry the gene for sickle cell and between 1 to 2% of births are of children with the condition. Despite this, there has been a general public health and social neglect of the condition, so that prevalence is poorly understood and policy non-existent. This participatory qualitative research project, conducted in 2018 in two districts in the country, sought to understand both women’s experiences caring for children with the condition, as well as what the needs were of women who had the condition. The findings illustrated that a historical memory of the condition and its effects exists in the intergenerational memories and practices of people. This is important to learn from to combat stigmatisation of women and people who have the condition. However, past expertise and medical knowledge currently co-exist in isolation from each other, with access to proper healthcare unavailable in most parts of the country. This has led to an inability to get a correct medical diagnosis, no advice about how to live with the condition and an inability to access specialized medical and rehabilitative services. These failures in care have led to early deaths and disablement, with the result that the general public fear the condition. A neglect of reproductive justice and the relational implications for women with the condition was also apparent in the high number of deaths of women and infants with sickle cell. Lastly, due to the work of the voluntary and medical sector, there is increasing awareness in parents, schools and communities of how the total environment is crucial for holistic management of sickle cell conditions in a low- income country. However, it is women who are still mostly responsible for ensuring that their children access a better quality of life and women who still incur moral blame and shame for their ill-health and that of their children.
... In Sierra Leone, it is estimated that one in four people carries the trait for sickle cell disease resulting in an estimated prevalence of 2% of SCD births, implying a very serious public health issue (Roberts et al. 2016). If a woman has sickle cell trait and her partner also has the trait, this means that in each and every pregnancy with that partner, there is a one in four chance of having a child with SCD (Atkin et al. 2015;Dyson 2019). ...
Article
In Sierra Leone, motherhood is being transformed into a moral career for women with sickle cell disorders. This qualitative participatory study, conducted in 2018, involved thirty-six semi-structured interviews with female care-givers and women with sickle cell disorders. Mothers argued that medical models of disease, combined with caring practices, are means to morally manage ideas of ‘spoiled identity’ and rethink the sick role, disability and life-outcomes of a potentially serious condition. Mothers encourage their children with sickle cell to stay in education as a route to access formal employment and careers that will not tax their bodies and ensure reproductive timing. Education and employment are framed temporally to ensure a delay so that girls can develop caring relationships and access motherhood safely. Understanding and encouraging the development of motherhood as a moral career, involving embodied hyper-vigilant caring practices, is valuable for the self-identity of mothers, allowing them to see a future for themselves and their children.
Article
Sickle cell disease (SCD) is a chronic genetic disease that causes life-threatening complications and requires robust comprehensive management. Developing comprehensive SCD programs in sub-Saharan African countries requires knowledge of the cultural factors affecting health-seeking behavior. We utilized an ethnographic approach and the frameworks of Dutta and Habermas to explore cultural factors influencing SCD management in rural Sierra Leone. A purposive sample of 27 individuals with SCD and their family and professional caregivers were observed and interviewed from March 2019 to April 2019. We identified four domains (Cultural Beliefs, Cultural Values, Cultural Practices, and Dealing with SCD) of cultural influences on SCD management, and 12 sub-themes (related to collectivism; spiritual, traditional, and Western beliefs and practices; and lived experiences) that reflect the personal, social, structural, and contextual complexities of SCD management. Further research regarding roles of traditional and spiritual leaders, combinations of Western and traditional practices, and culturally centered interventions is warranted.
Article
Full-text available
It has been 100 years since the first report of sickle haemoglobin (HbS). More than 50 years ago, it was suggested that the gene responsible for this disorder could reach high frequencies because of resistance conferred against malaria by the heterozygous carrier state. This traditional example of balancing selection is known as the 'malaria hypothesis'. However, the geographical relationship between the transmission intensity of malaria and associated HbS burden has never been formally investigated on a global scale. Here, we use a comprehensive data assembly of HbS allele frequencies to generate the first evidence-based map of the worldwide distribution of the gene in a Bayesian geostatistical framework. We compare this map with the pre-intervention distribution of malaria endemicity, using a novel geostatistical area-mean comparison. We find geographical support for the malaria hypothesis globally; the relationship is relatively strong in Africa but cannot be resolved in the Americas or in Asia.
Article
Full-text available
Approximately 280,000 children are born with sickle cell anemia (SCA) in Africa annually, yet few survive beyond childhood. Falciparum malaria is considered a significant cause of this mortality. We conducted a 5-year prospective surveillance study for malaria parasitemia, clinical malaria, and severe malarial anemia (SMA) in Dar-es-Salaam, Tanzania, between 2004 and 2009. We recorded 10,491 visits to the outpatient clinic among 1808 patients with SCA and 773 visits among 679 patients without SCA. Similarly, we recorded 691 hospital admissions among 497 patients with SCA and 2017 in patients without SCA. Overall, the prevalence of parasitemia was lower in patients with SCA than in patients without SCA both at clinic (0.7% vs 1.6%; OR, 0.53; 95% CI, 0.32-0.86; P = .008) and during hospitalization (3.0% vs 5.6%; OR, 0.46; 95% CI, 0.25-0.94; P = .01). Furthermore, patients with SCA had higher rates of malaria during hospitalization than at clinic, the ORs being 4.29 (95% CI, 2.63-7.01; P < .001) for parasitemia, 17.66 (95% CI, 5.92-52.71; P < .001) for clinical malaria, and 21.11 (95% CI, 8.46-52.67; P < .001) for SMA. Although malaria was rare among patients with SCA, parasitemia during hospitalization was associated with both severe anemia and death. Effective treatment for malaria during severe illness episodes and further studies to determine the role chemoprophylaxis are required.
Article
Full-text available
Sickle cell disease (SCD) compromises host immune defence and predisposes to infections from several encapsulated bacteria, viruses and parasites. While penicillin prophylaxis and pneumococcal vaccination are established routine care in developed countries, such preventive measures are poorly structured or non-existent in most malaria-endemic, developing country settings. In fact, the role of pneumcoccal infections has been brought into question, based on available data. The role of invasive pneumococcal disease in child mortality has now been established from population-based studies in such settings. Thus, it may be unsafe to assume that children with SCD are less susceptible. Whether malaria endemicity increases susceptibility to other encapsulated bacteria such as salmonella infections is a critical but unanswered question that will inform the development of appropriate preventive measure policies in this setting. Research to clearly define the leading cause of infection-related morbidity and mortality in SCD in Africa should be encouraged.
Article
Full-text available
Sickle cell disease complications are an important mortality cause in children mainly in Africa and India. Notwithstanding the magnitude of the problem on the African continent, studies identifying factors related to the adverse outcomes of sickle cell disease in the pediatric population are still scarce. To identify prognostic factors associated with mortality in children and adolescent aged under fifteen years with diagnosis of sickle cell disease. Patients meeting inclusion criteria were listed and randomly selected. Clinical and laboratory data collected at time of admission were collected from medical records through the use of standard forms. The association between mortality and explanatory variables was tested using univariable and multivariable analysis. The overall mortality rate was 64 (12.9%), and bacterial infections 26 (40.1%) were the most common cause of death. Place of residence out of Luanda, lack of outpatient follow-up, symptoms onset more than three days, disease manifestation before age of eighth months and hemoglobin level of < 7 g/dl were independent risk factors related to death. In the study population, sickle cell related deaths were related to quality of health care and access to care. The creation of regional sickle cell disease centers to support those afflicted by the disorder and their families would contribute to reduce the burden associated with the disease.
Article
To demonstrate a method for using genetic epidemiological data to assess the needs for equitable and cost-effective services for the treatment and prevention of haemoglobin disorders. We obtained data on demographics and prevalence of gene variants responsible for haemoglobin disorders from online databases, reference resources, and published articles. A global epidemiological database for haemoglobin disorders by country was established, including five practical service indicators to express the needs for care (indicator 1) and prevention (indicators 2-5). Haemoglobin disorders present a significant health problem in 71% of 229 countries, and these 71% of countries include 89% of all births worldwide. Over 330 000 affected infants are born annually (83% sickle cell disorders, 17% thalassaemias). Haemoglobin disorders account for about 3.4% of deaths in children less than 5 years of age. Globally, around 7% of pregnant women carry b or a zero thalassaemia, or haemoglobin S, C, D Punjab or E, and over 1% of couples are at risk. Carriers and at-risk couples should be informed of their risk and the options for reducing it. Screening for haemoglobin disorders should form part of basic health services in most countries.
Article
The number of individuals with sickle cell disease (SCD) in the U.S. is unknown. Determination of burden of disease, healthcare issues, and policies is best served by representative estimations of the SCD population. To update SCD population estimates by using recent U.S. Census and birth-cohort SCD prevalence for at-risk populations as available through the centralized reporting of universal newborn screening for hemoglobinopathies, with an effort to demonstrate the potential effect of early mortality. National and state SCD populations were estimated based on the 2008 U.S. Census, using total, African-American, and Hispanic birth-cohort disease prevalence derived from the National Newborn Screening Information System. Estimates were corrected for early mortality for sickle cell anemia using data from the CDC's Compressed Mortality Report and published patient-cohort survival information. National SCD population estimates ranged from 104,000 to 138,900, based on birth-cohort disease prevalence, but from 72,000 to 98,000 when corrected for early mortality. Several limitations were noted in the available data, particularly for SCD mortality in adults. The number of individuals with SCD in the U.S. may approach 100,000, even when accounting for the effect of early mortality on estimations. A paucity of high-quality data limits appropriate estimation. State-to-state variability may preclude application of state-specific information to other states or to the nation as a whole. Standardized collection and centralized reporting, a surveillance system, will be necessary to assess the size and composition of the U.S. SCD population.