Health Related Quality of Life among Children with Sickle Cell Anaemia in Northwestern Tanzania

Background: Sickle cell anaemia (SCA) is a serious, multisystem, genetic disorder affecting millions of children worldwide. The disease causes numerous complications that interfere with the health-related quality of life (HRQoL) of these children including an impact on educational, physical and psychosocial development. Few studies have described the clinical spectrum and quality of life of children with SCA living in a low-resource area. Objectives: This study aimed to determine the clinical spectrum and HRQoL among children living with sickle cell anaemia (SCA) in northwest Tanzania. Methods: This hospital-based cross-sectional study took place at Tertiary and teaching hospital, Bugando Medical Centre, Mwanza Tanzania. The study enrolled children ages 2 – 12 years old with SCA attending the Bugando Medical Centre sickle cell clinic. Health related quality of life was measured using the Pediatric Quality of Life, Brief Generic Core Scale after translating from English into a Swahili version. Important SCA complications were assessed using a structured questionnaire. Results: From October 2016 to March 2017, 204 children were enrolled. Participants presented at a median age of 6 years [IQR 4 – 9]. Among children with SCA the most common clinical signs at the time of enrolment were pale in 69.6% (142/204), jaundice in 65.9% (134/204), oxygen saturation < 90% in 25% (51/204) and splenomegaly in 19% (39/204). Severe anaemia was observed in 30.9% (63/204). A majority reported vaso-occlusive crisis (166/204, 81.4%), and very few had experienced a prior stroke (5/204, 2.5%). Using a modified Likert scale, a total of 41/204 (20.1%) children had poor HRQoL indicated by low scores on PedsQL™ and 163/204 (79.9%) children had high scores, indicating good HRQoL. On multivariate analysis, age ≥ 5 years (p-value < 0.001), haemoglobin < 7 g/dl (p-value = 0.001) and >3 hospitalizations per year (p-value = 0.008) were associated with poor HRQoL. Conclusion: SCA complications, negatively impact the HRQoL of children living with the disease. Severe anaemia, older age and frequent hospitalizations were highly associated with poor HRQoL. Comprehensive management is needed beginning at diagnosis to identify these children early and provide them with adequate support.


Introduction
Sickle cell anemia (SCA) is a genetic disorder with many physical manifestations.The clinical course is characterized by periods of quiescence and exacerbation, but hallmarks of the disease include chronic haemolytic anaemia, infection, and vaso occlusive episodes that cause acute pain, acute chest syndrome, and damage to cerebral vasculature that increases the risk of stroke [1] [2] [3].
The physical manifestations of SCA have a significant impact on quality of life (QoL).QoL is a person's ability to perform the ordinary tasks of daily living.It moves beyond direct manifestations of illness to the patient's personally experienced morbidity.Assessment of QoL is an important aspect of chronic disease management [2].Children with SCA may have restrictions placed on their physical activities such as performing household chores, play, or self-care [3].Exacerbations and hospitalizations may impede school attendance and lead to compromised physical, psychological and cognitive function, particularly attention and learning problems in children [4].
SCA is common in sub-Saharan Africa, but its complications and effect on QoL in the African setting are poorly understood.Physical manifestations that affect QoL in SCA are particularly common in sub-Saharan Africa.Northwest Tanzania has a particularly high prevalence of SCA and a high burden of associated complications [5] [6] [7] [8].Children in such settings receive a basic package of preventive measures (penicillin, mosquito bed nets, folic acid), but the bulk of the care is focused on symptomatic management of disease exacerbations and complications.While several studies have demonstrated the effect of SCA on QoL in children living with SCA in the USA, little is understood about SCA and QoL in sub-Saharan Africa [9] [10] [11].Psychosocial needs are rarely assessed or addressed in daily practice.
Therefore, we set out to determine the clinical spectrum and Health Related Quality of Life (HRQoL) among children living with SCA in northwest Tanzania so that we could better understand the usefulness of assessing HRQoL in daily practice.Our secondary objective was to determine factors associated with poor HRQoL so that targeted therapies could be provided to prevent worsening of HRQoL.With a proper understanding of the severity of the problem and its associated factors, appropriate services such as cognitive-behavioural therapy, occupational therapy, or physical therapy, could be arranged for patients earlier in their disease course.

Study Area and Recruitment
This was a hospital-based cross-sectional study that was conducted among children with SCA attending the outpatient paediatric clinic at Bugando Medical Centre (BMC) in northwest Tanzania.BMC is a zonal referral hospital as well as a consultant and tertiary specialist teaching hospital responsible for care of all the Lake and Western Zones of the United Republic of Tanzania.The catchment area includes nine regions with a population of approximately 16.2 million people (see Figure 1).BMC has a paediatric sickle cell clinic with >500 children enrolled.The clinic runs twice a week, and about 50 patients are seen on a weekly basis.Most of the children initially report to the clinic after development of complications such as dactylitis, recurrent fever, or vaso-occlusive crisis.
Children with SCA, genotype HbSS, from 2 to 12 years old attending SCA clinic at BMC were eligible for the study.We excluded all hospitalised children with SCA.After written informed consent was obtained from the parents or guardians, demographic and clinical information were collected using a standardized questionnaire.A complete physical examination of each child was performed, including measurements of weight and height using a standardized WHO chart, and BMI was calculated.Nutritional status Z-score was determined for each child.

Health Related Quality of Life
The Pediatric Quality of Life (PedsQL ™ ) Brief Generic Core Scale was used (after translating from English to Swahili) to measure HRQoL for each child [12].For children 2 -4 years old, the parental proxy questionnaire was used, while for children 5 -12 years old a self-report questionnaire was used [13].The PedsQL ™ Brief Generic Core Scale is composed of 23 questions about problems with different aspects of daily life in 4 different domains: physical functioning, social functioning, emotional functioning, and school functioning.The questions within each domain are answered using a Likert scale from 0 (never a problem) to 4 (almost always a problem), so that higher scores suggest a lower HRQoL.
For ease of statistical evaluation and interpretation, the scores were reversed and transformed to a 0 -100 scale so that higher scores indicate better HRQoL.The initial 0 -4 Likert scale values were reversed and converted to 0 -100 as follows: 0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0.A final score for each domain was calculated by dividing the sum of the scores for a domain by the number of questions within that domain.A total score was calculated in the same fashion by taking the sum of all scores in the questionnaire by the number of questions in the questionnaire.Using this method, the established cut off below which a child is considered to have poor quality of life is 69.7 for children 5 -12 years old who are self-reporting and below 65.4 for parental proxy reporting among children of 2 -4 years [13].

Laboratory Methods
Peripheral venous blood was collected in ethylene diamine tetra-acetic acid (EDTA) tubes at enrolment from all eligible children.A complete blood count (CBC) including haemoglobin concentration, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), red blood cell count, reticulocyte count, leucocyte count and platelet count were determined using a Mindray BC 3200 Haematology Analyser (Mindray, Nanshan, Shenzhen, China).

Data Analysis
Data was entered into Microsoft Excel (Microsoft, Redmond, Washington, U.S.A.) and was exported to Stata version 13 (StataCorp LLC, College Station, Texas, U.S.A.) for analysis.Continuous data were summarized using means and standard deviations (SD) or medians and interquartile ranges [IQR] while categorical data were summarized using proportions.Anaemia was categorized according to the World Health Organization as severe anaemia (<7.0 g/dL), moderate anaemia (7.0 -9.9 g/dL), or mild anaemia (10.0 -10.9) [14].HRQoL was initially recorded as a continuous variable and then categorized as either poor QoL or good QoL.To determine factors associated with poor HRQoL, univariate logistic regression was performed.Factors with a p-value less than 0.1 in univariate logistic regression model were then subjected to multivariate logistic regression analysis.Factors with a p-value of less than 0.05 were considered to be independently associated with HRQoL.

Enrolment Procedure
From October 2016 to March 2017, there were 807 outpatient visits in the BMC sickle cell clinic.After exclusion of repeat visits and children with HbAS, 213 children with SCA were eligible for the study.A total of 204 consented and were enrolled into the study (see Figure 2).
Their median age was 6 [4 -9] years and males comprised 61.3% (125/204).The median age at which children reported having initially presented to the sickle cell clinic with signs and symptoms of SCA was 12 months [ .Most of the children (90.2%, 184/204) were brought by their parents to the sickle cell clinic (Table 1).

Discussion
In this study, we sought to evaluate the HRQoL of children with SCA attending an outpatient clinic in Tanzania.HRQoL can be affected by local sociocultural context in addition to disease-specific factors.Globally, SCA is most prevalent in sub-Saharan Africa, and within Tanzania the Northwestern region around this clinic has the highest prevalence of the disease, [5] [6] [7] [15] with 21% of children carrying the sickle cell gene (HbAS), and more than 1% having SCA [7] [15].We previously described the complications experienced by patients in this setting, [8] but few studies have touched on the impact that SCA has on HRQoL in paediatric populations in low-resource settings of sub-Saharan Africa.We found that 20% have a poor HRQoL, and that the median HRQoL score in this group was 78.
Few studies of HRQoL in children with SCA have been performed in sub-Saharan Africa in general or Tanzania specifically.The few studies that have attempted to measure the impact of SCA on quality of life have focused on adolescents and adult patients or caregivers of children with SCA [16].Many studies have been conducted in high resource settings that describe HRQoL for SCA [17].In general, the HRQoL in these other studies is worse than the HRQoL that we describe.Our findings are even more astonishing when comorbidities of the children enrolled are taken into consideration: 30.9% of the children had severe anaemia, and 12.7% of children had malnutrition.Both of these should tend to decrease their quality of life.
The higher than expected HRQoL found in our study might be related to the population that we enrolled or the suitability of the instrument that we used.The PedsQL has been validated in the paediatric SCA population [18], but it has not been validated in the sub-Saharan African context.We enrolled a younger population than some studies, but very few of them had received disease modifying therapy with hydroxyurea, so they will have encountered the same number of acute complications as children in other settings, even if they have not acquired the same degree of chronic complications [19].Finally, younger children's results were reported through parental proxy.It is unclear how the sociocultural context might influence parents' answers to some of the questions on the PedsQL.
We identified several predictors of HRQoL in our study.Severe anaemia, recurrent hospitalizations, severe malnutrition, and age ≥ 5 years were all associated with a worse quality of life.In the US, Hooker [20] concluded that children who had higher haemoglobin had better HRQoL than those who had lower haemoglobin.Additionally, in a study by Brewer et al., SCA children who had history of blood transfusion had worse HRQoL compared to those who had not previously received a transfusion.In a low-resource setting, it is unclear how much concomitant nutritional deficiency and/or malarial infections might contribute to the severity of anaemia and overall health state, but regardless of the origin of anaemia, lower haemoglobin correlates with poor HRQoL.SCA disease modification with hydroxyurea improves the baseline haemoglobin and would likely improve the HRQoL through both improved haemoglobin concentration and fewer SCA related clinical events.
In addition, Age ≥ 5 years was found to be associated with poor HRQoL.This finding is consistent with several studies that have shown an increasing age has a negative correlation with HRQoL [10] [20] [21].This may be attributed to an increase in severity of SCA as the patients mature with more acute events such as vaso-occlusive crisis and chronic complications.
Our study participants showed the lowest score on school functioning had the lowest scores, Similar to study done by Menezes et al. [22] and Dampier et al. [19] had lower scores in school functioning.In addition, studies done by Hooker et al. [20] and Dampier et al. [19] in America had showed lower scores in physical domain.In our study children who had history of hospitalization had lower mean score for school functioning than those who were not hospitalized.Furthermore history of recurrent hospitalizations was associated with poor HRQoL this was consistent with other studies done by Dale et al. [23] and Dampier et al. [19].

Possible Interventions That Could Improve Quality of Life
In order to improve the quality of life to our sickle cell population, there is a great need of Incorporating HRQoL assessment tool in our guidelines so as to identify children with poor HRQoL and to intervene early by providing a comprehensive cognitive, behavioral therapy, occupational therapy, and physical therapy.
Our study limitations are due to lack of optimization of questionnaire in African children, as we had a younger population that has not acquired the same degree of poor QoL also in parental perspectives the parent proxy was not reliable.

Conclusion
This study has shown severe anaemia, older age, malnutrition and frequent hospitalizations were highly associated with poor HRQoL in a high number of children with sickle What is the level of education of the caretaker?Open J Blood Dis.Author manuscript; available in PMC 2023 November 29.

Figure 2 .
Figure 2. Enrollment procedure of children with Sickle cell children attended in the clinic during the study period October 2016-march 2017.

Figure 3 .
Figure 3. Percentage of SCA complications of 204 children with sickle cell anaemia attended in the clinic during the study period October 2016-March 2017.

Table 1 .
Demographic and clinical characteristics of 204 children with sickle cell anaemia seen at Bugando medical centre clinic from October 2016 to March 2017.
Open J Blood Dis.Author manuscript; available in PMC 2023 November 29.

Table 2 .
Common clinical presentation of 204 children with sickle cell anaemia attended in the clinic during the study period October 2016-march 2017.
Open J Blood Dis.Author manuscript; available in PMC 2023 November 29.

Table 3 .
Health related quality of life of 204 children with sickle cell anaemia attended in the clinic during the study period October 2016-March 2017.