Incidence of clinical malaria and asymptomatic parasitaemia among African children living with sickle cell disease: a multicentre prospective longitudinal cohort study protocol

Abstract

Introduction

Sickle cell disease is a monogenic blood disorder prevalent in Africa, where malaria poses a health risk for affected individuals. Individuals with sickle cell disease are susceptible to malaria, which can be complicated by vaso-occlusive episodes, severe anaemia and death. Understanding the intersection of malaria and sickle cell disease in African countries with high co-prevalence is essential for developing effective management and prevention strategies, including clinical guidelines on the use of malaria chemoprophylaxis in this population. This study will determine the monthly incidence of malaria in children living with sickle cell disease in each of two clusters of African countries.

Methods and analysis

This 1-year observational study will enrol 2808 children with sickle cell disease, aged 6 months to 17 years, at Sickle Pan-African Research Consortium clinical sites in Ghana, Mali, Nigeria (West), Tanzania, Uganda, Zimbabwe and Zambia (East-South). Malaria infection will be assessed at monthly visits and unscheduled sick visits over 12 months. Data collected will include socio-demographic characteristics, beta-globin genotype, medical history, clinical symptoms and malaria blood smear or rapid diagnostic test results. The primary outcome is monthly incidence of clinical malaria; a secondary outcome is incidence of asymptomatic malaria.

Ethics and dissemination

This study was developed with input from patients with sickle cell disease and their caregivers. The study will be conducted according to the principles of the Declaration of Helsinki. Written informed consent from guardians and assent from child participants age 7 or above will be provided before enrolling in the study. This protocol has been reviewed and approved by local and national ethics committees at each study site. The findings of this study will be provided to participants and the general public through presentations at the annual Sickle Cell Day community events at each study site, local media and open access publication in peer-reviewed journals.

The full names of the ethics committees are as follows. Ghana: Komfo Anokye Teaching Hospital Institutional Review Board; Mali: Ethics Committee of the University of Sciences, Techniques and Technologies of Bamako; Nigeria: National Health Research Ethics Committee of Nigeria; Tanzania: Muhimbili University of Health and Allied Sciences Research Ethics Committee and National Health Research Ethics Committee; Uganda: Makerere School of Medicine Research and Ethic Committee; Zambia: National Health Research Authority and Excellence in Research Ethics and Science Converge Institutional Review Board; and Zimbabwe: Joint Research Ethics Committee and the Medical Research Council of Zimbabwe.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

WHAT THIS STUDY ADDS

• This study will provide estimates of clinical malaria incidence among children with sickle cell disease in seven different African countries over a 12-month period. Furthermore, blood smears and blood spots will be collected to determine the incidence of asymptomatic parasitaemia—a condition that could develop into symptomatic malaria or serve as a source of malaria transmission.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• This study will provide epidemiological data to guide local decisions regarding malaria prevention and treatment for children living with sickle cell disease.

Introduction

Globally, the number of infants born with sickle cell disease (SCD) increased from an estimated 453 000 in 2000 to 5 15 000 in 2021, reflecting a 14% rise over two decades corresponding to a global birth rate of 382 cases per 100 000 live births (95% CI 316 to 456). Notably, about 75% of these births occur in Africa, highlighting the continent’s disproportionate share of the global burden.^1–3 Individuals living with SCD are susceptible to severe infections, particularly malaria, with the most vulnerable group being children under 5 years of age, adolescents and pregnant women.^4–6

The geographical distribution of SCD overlaps with that of malaria, with both diseases being frequent in Africa south of the Sahara.^3,7 This parallel in epidemiology is not coincidental, as sickle cell trait (ie, heterozygosity for the sickle cell allele) is protective against malaria-related mortality.^8–10 However, people living with homozygous SCD are susceptible to malaria and malaria infection can complicate SCD.

Malaria has been found to worsen the pre-existing haemolytic anaemia in people living with SCD.¹¹ People living with SCD often have impaired splenic function,¹² which hinders the clearance of parasitised red blood cells. Malaria parasites attach to capillaries and cause vascular endothelial cell activation, which can trigger vaso-occlusive episodes. In endemic areas, malaria is a significant cause of hospitalisation and mortality in children with SCD.^13–16 Children hospitalised with malaria are more likely to die if they have SCD.^4,5,17 Studies have demonstrated that malaria is associated with increased life-threatening conditions in people living with SCD,^18–20 and that patients with SCD are at increased risk of dying from malaria due to severe anaemia.^4,5,18

In contrast to prior studies, a recent secondary analysis of malaria outcomes in the Transfusion and Treatment of African Children Trial (TRACT) study suggested reduced malaria infection risk among those with SCD compared with those without SCD.²¹ In addition, the TRACT study found fewer severe malaria complications like cerebral malaria and less risk of death at 28 days follow-up among those with SCD, although severe anaemia was more frequent. Given the potential severity of malaria complications in patients with SCD in Africa, the WHO recommends that individuals living with SCD in endemic areas receive antimalarial prophylaxis to prevent clinical malaria episodes.²² Despite the impact of malaria on SCD, there is a lack of comprehensive epidemiological data on malaria incidence among people living with SCD. To guide best practices for malaria prevention, a prospective, multicountry cohort study is needed to better understand malaria epidemiology in people living with SCD.

The objective of this study is to describe the incidence of clinical malaria and asymptomatic parasitaemia among children with SCD who are part of the Sickle Pan-African Research Consortium (SPARCo), a well-defined registry of over 34 000 individuals with SCD. This established longitudinal cohort presents an opportunity to understand the epidemiology of malaria among children living with SCD. The knowledge gained from this study will guide strategies to lower malaria incidence and reduce malaria-attributable morbidity and mortality among children living with SCD in Africa south of the Sahara.

Patient and public involvement

People living with SCD plus their family members, caregivers and members of the public came together and advocated for the creation of the Centre de Recherche et de Lutte Contre la Drepanocytose (CRLD). In 2008 it was created by law, and in 2010 opened its doors to patients.

The CRLD is a comprehensive sickle cell centre that provides patient care, education, research and advocacy for people living with SCD in Mali and currently cares for more than 20 000 adults and children with SCD. The patient advocacy group advises the CRLD throughout the year as well as when new research studies or care policies are proposed. This interaction takes place through routine scheduled meetings such as the CRLD ethics committee and the university ethics committees, which include members of the community, patient representatives and religious leaders in addition to legal, healthcare and science professionals. Similar engagement practices take place at each consortium site.

The decision to study malaria incidence was driven by questions raised by patients and their families around the risk of contracting malaria, its potential severity and whether chemoprophylaxis is needed. The SickleInAfrica Consortium met in Bamako, Mali in May 2024 specifically to discuss this study protocol. Patients with SCD participated in that meeting, speaking on behalf of the patients with SCD population and addressing issues such as the relevance of the research question, the study design and the benefits and burdens of participating. Patients noted that monthly visits for malaria testing throughout the year were burdensome, especially for families with young children, but emphasised that the short study duration and the insights gained into malaria incidence would ultimately benefit individuals with SCD, making the effort worthwhile. This meeting also produced radio and television broadcasts to make the public aware of the proposed research activities.

The dissemination of the study results will take place through the annual World Sickle Cell Day (June 19) at each consortium site and through patient support group representatives that are affiliated with the SickleInAfrica consortium. In addition, we will publish reports on the centre websites and in publicly accessible peer-reviewed journals. We will continue to engage directly with patients and their caregivers throughout the study and will assess their preferences regarding methods for disseminating the research findings. This clinical study protocol will address patient concerns about the risk and severity of malaria for children with SCD.

Methods and analysis

Study design

This is a 1-year prospective observational study of patients with SCD at the SPARCo sites’ clinics in Ghana, Mali, Nigeria, Tanzania, Uganda, Zimbabwe and Zambia. The primary outcome is malaria incidence. The study start and expected end dates (month, year) are as follows, ordered by start date (table 1).

Table 1. Study start and expected end dates.

Country	Start	Expected end
Mali	December 2024	September 2026
Tanzania	March 2025	February 2027
Uganda	June 2025	October 2026
Ghana	July 2025	January 2027
Zimbabwe	July 2025	December 2026
Zambia	July 2025	October 2026
Nigeria	July 2025	October 2026

Study population

The study population will include patients with SCD aged 6 months to 17 years enrolled in the SickleInAfrica registry, including new enrollees for the next one (1) year. For each site, patient data will be extracted from the registry based on predefined inclusion and exclusion criteria. The extracted data will be stratified by age category, and participants will then be selected using a simple random sampling method within each stratum.

Inclusion criteria

• SCD, defined as homozygosity for the beta globin S allele (SS), compound heterozygosity for the S and C alleles (SC), or compound heterozygosity for the S- and beta thalaessemia alleles (Sß-thal), as determined by molecular analysis of protein, DNA, or by a validated point of care device.

• Age: 6 months to 17 years. (Up to 15 years in Mali.)

• Attendance at one of the SickleInAfrica clinical sites.

• Willingness to comply with study procedures.

• Willingness to participate and sign a written consent and/or assent form.

• For minors aged 7 years and older, the parent or guardian’s written informed consent and the participant’s assent (where possible) will be obtained.

Exclusion criteria

• Inability to comply with study procedures based on assessments by the local study team and site principal investigator (PI).

• Individuals presenting with signs and symptoms of malaria, in whom the diagnosis of malaria is confirmed with a diagnostic test, will not be enrolled. They will be treated for malaria and invited to return in 28 days for enrolment.

Screening, eligibility and assessments

Study participants will be enrolled from a list of participants on the SPARCo registry. Children will be enrolled after the parents give informed consent and the child, if able, assents to participate in the study. Initially, they will be screened, and eligible ones will be enrolled in the study. Screening for eligibility will be conducted until the required sample size is attained for each study site. Participants who cannot return for follow-up as per the schedule will not be enrolled. A screening log will be kept. Enrolled patients will be scheduled for monthly clinical visits, during which all will undergo malaria screening using standardised methods. Each visit will include a full physical examination, collection of vital signs data and a complete blood count (figure 1 and table 1). Patients presenting with signs or symptoms of malaria will undergo confirmatory testing with a blood smear or malaria rapid diagnostic test (MRDT), and results will guide treatment decisions based on established clinical guidelines. For patients without signs or symptoms of malaria, blood smears will be collected, stored under appropriate conditions and analysed later to detect asymptomatic malaria as part of the secondary outcome assessment. Patients presenting for unscheduled visits will undergo the same malaria screening and diagnostic procedures as scheduled visits. Patients meeting the criteria for a malaria case at a scheduled or unscheduled visit will be treated based on each country’s guidelines. Dried blood spots (DBS) will be collected at all patient visits and stored under controlled conditions for later research analysis, including submicroscopic malaria detection by PCR and molecular genotyping of parasites to identify drug-resistance markers. At each visit (scheduled and unscheduled), SCD complications such as vaso-occlusive episodes and anaemia will be evaluated for an association with clinical malaria cases.

Figure 1. Flow chart of study visit describing clinical evaluation, laboratory testing and decision-making.

Signs and symptoms of malaria

Recognising that the signs and symptoms of malaria are non-specific, our provisional diagnosis of malaria will primarily be based on fever or history of fever.^13,22 Any patient presenting with a body temperature greater than or equal to 37.5 degrees will undergo laboratory testing using MRDT and blood smear. In addition to fever, the following signs and symptoms, if acute, can also prompt laboratory testing for malaria: lethargy, nausea, vomiting, abdominal cramps, muscle aches or somnolence.²²

Scheduled visits

Study participants will be followed at 1-month intervals for 1 year (12 months), and all clinical events will be recorded (table 2).

Table 2. Study schedule of activity.

Activity	Monthly visits
	0	1	2	3	4	5	6	7	8	9	10	11	12
Medical history	x	x	x	x	x	x	x	x	x	x	x	x	x
Screen for malaria clinical symptoms	x	x	x	x	x	x	x	x	x	x	x	x	x
Physical examination	x	x	x	x	x	x	x	x	x	x	x	x	x
Nutrition history	x						x						x
Laboratory test (CBC)	x			x			x			x			x
Blood smear (thick and thin)*	x	x	x	x	x	x	x	x	x	x	x	x	x
Dry blood spots on filter paper	x	x	x	x	x	x	x	x	x	x	x	x	x
HbF levels	x

^*Blood smear interpretation for children with symptoms of malaria will be performed in real-time as per standard of care. For children without symptoms of malaria, blood smears will be analysed at a later date.

CBC, complete blood count; HbF, Fetal hemoglobin; HPLC, High-performance liquid chromatography.

Unscheduled visits

Participants will be instructed to come to the study-specific SCD clinic for any health problems that arise during the study. If signs or symptoms of malaria are present, blood samples will be collected for malaria diagnosis (eg, MRDT or blood smear). DBS for research will also be collected. Malaria cases will be further evaluated and treated as per local guidelines. After an unscheduled visit, the participant will resume routine scheduled visits (if the next visit is at least 5 days from the unscheduled visit).

Demographic, clinical and laboratory data

Baseline information obtained will include socio-demographic data: age, sex and residential address, socio-economic status of the parents and data for the use of insecticide treated bed net. Other clinical data to be obtained at predetermined intervals will include their haemoglobin concentration, white blood cell count with differential, quantitative and qualitative assessment of pain, number of hospital/clinical admissions since last visit and clinically diagnosed malaria (fever, chills and headache), WHO malaria severity, MRDT positivity, total number of transfusions and total number of admissions. Moreover, patient comorbidities and all medications used by patients will be recorded. The use of all medications for the management of SCD, such as hydroxyurea, folic acid and malaria chemoprophylaxis (MCP) will be recorded throughout the study period.

Sample size

Sample size was determined based on the primary outcome of estimating and comparing monthly malaria incidence among children and adolescents with SCD over a 12-month follow-up period. To detect a 5% difference in incidence between months when the incidence ranges from 5% to 25% (table 3),²³ with a significance level of 5%, up to 20% loss to follow-up, and ignoring the correlation within a participant over time, 1404 participants are required to achieve 80% power. We aim to achieve this sample size by grouping countries with similar patterns of malaria periodicity into two geographical clusters: namely West (Ghana, Mali and Nigeria) and East-South (Tanzania, Uganda, Zimbabwe and Zambia). We will enrol approximately 1404/3=468 participants from each country, with the exceptions of Zimbabwe and Zambia that will enrol 234 participants each. This sample size of 1404 participants per cluster also provides adequate power to test for a 5% difference in incidence between the two geographical clusters with a power of 80%, at an incidence rate of 15%, an HR of 1.4, and up to 10% loss to follow-up.

Table 3. Estimated sample size at different malaria incidence scenarios.

		Expected outcome proportion (reference month)
		0	0.05	0.1	0.15	0.2	0.25
Expected outcome proportion (test month)	0	–	225	108	69	49	38
	0.05	225	–	579	192	104	68
	0.1	108	579	–	894	265	135
	0.15	69	192	894	–	1168	329
	0.2	49	104	265	1168	–	1404
	0.25	38	68	135	329	1404	–

Data collection and management

Data will be collected using paper case report forms, or via a mobile Research Electronic Data Capture (REDCap) module and subsequently entered into the REDCap database. Malaria blood smear results will be independently interpreted by two trained microscopists. Discordant results will be resolved by a third reviewer. Blood smears and MRDTs will be interpreted in real-time for symptomatic patients, while for asymptomatic patients, blood smears will be collected, stored under appropriate conditions and analysed later.

The team leader will conduct daily reviews of the data collected for accuracy and completeness using standardised checklists and address any queries from the data manager. Data cleaning and validation will be conducted continuously, following SickleInAfrica standard operating procedures.

Data analysis

All analyses will be performed according to the follow-up time for the study participants. Malaria positivity at the initial visit will not be included in the incidence measurements. After a malaria case is treated, 4 weeks will be subtracted from the at-risk time to account for anti-malarial treatment effect. No adjustment will be made for prophylactic doses of anti-malarial drugs. Both unadjusted and adjusted analyses will be reported. HRs and incidence rates will be calculated and presented with 95% CIs. The estimates will be compared by study site, use of MCP and hydroxyurea and across different age categories. All analyses will adjust for age as a confounding variable. Age will be categorised into three groups: 0–4, 5–9 and 10–17 years, with the 10–17 age group serving as the reference category. Data analysis for all outcomes will be stratified by study site and age group categories.

In the event of loss to follow-up, data will be censored at the last visit. Loss to follow-up is defined as failure to attend three consecutive scheduled visits with no contact. All estimates will be reported with 95% CIs, and a two-tailed p value of <0.05 will be considered statistically significant.

Primary outcome

Incidence of malaria

Clinical malaria is defined as malaria-related symptoms (fever (axillary temperature ≥37.5°C), chills, severe malaise, headache or vomiting) at the time of examination or 1–2 days prior to the examination in the presence of a Plasmodium falciparum-positive blood smear. The monthly incidence of malaria over 12 months will be the primary outcome variable. This will be estimated as the total number of malaria cases over the total sum of follow-up time for the study participants expressed per 1000 person-years. Time to the first malaria case will also be analysed using Cox regression model, for all ages by sites/countries. Kaplan-Meier survival curves will be used to compare malaria-free survival across different categorical variables (eg, age groups, MCP use and hydroxyurea use).

Since some participants may experience multiple malaria episodes during follow-up, recurrent malaria events will be analysed using a mixed-effect negative binomial regression model. This model will account for overdispersion and repeated malaria events within individuals.

Secondary outcomes

Incidence of asymptomatic parasitaemia

The incidence of asymptomatic parasitaemia will be estimated as the total number of positive blood smear events in individuals not reporting concurrent symptoms over the total number of study participants. Mixed-effect negative binomial models will be used.

Incidence of submicroscopic parasitaemia

The incidence of submicroscopic infection over the 12 months will be estimated as the total number of confirmed PCR-positive through a dried blood spot sample event during the study period over the total number of study participants. These data will be used for research and not for clinical care decisions. Mixed-effect negative binomial models will be used. In addition, dried blood spot can be used for molecular genotyping of parasites to assess antimalarial resistance and for analysis of parasite genetic diversity.

Severity of malaria in patients with sickle cell disease

Severe malaria will be defined by WHO criteria. The incidence of severe malaria will be estimated as the number of severe malaria events observed throughout the study period divided by the total follow-up time and presented per 1000 person-years. We will present the number of severe malaria events (overall and by severe malaria complication) over the total number of clinical malaria cases observed during the 1-year follow-up. Negative binomial models will be used.

Sickle cell disease complications associated with malaria

SCD complications will be recorded using case report forms, integrating data from history, physical and laboratory testing data available from each patient visit. The incidence of SCD complications such as vaso-occlusive episodes, acute chest syndrome, priapism and healthcare resource utilisation, including clinic and hospital visits, will be compared at malaria case visits versus non-malaria case visits using incidence rate ratios and 95% CIs.

Temporal patterns of malaria incidence

To identify temporal patterns in malaria incidence over 12 months period we will carry out analyses (Cox and/or negative binomial regression models) against time (month or grouped into December to February (short dry season in Eastern), March to June (long rainy season in Eastern) as explanatory variable to define a temporal variation in malaria transmission. The analysis will be stratified by sites with aims of depicting the monthly/seasonal variation in the incidence of clinical malaria and 95% CIs will be calculated to assess the precision of incidence estimates. The impact of clustering within sites will be considered using robust SEs or mixed-effects models to account for site-level variability.

Risk factors associated with malaria susceptibility and severity

Risk factors associated with the outcome variables, as identified in the univariate models outlined in the previous subsections, will be included in multivariate models to determine the factors most strongly associated with the outcome. These models will consider various factors, including socio-demographic data, nutritional indices, physical examination and laboratory findings and the reported use of preventive measures such as mosquito nets and MCP.

Clustering by study site

To account for site-level clustering and heterogeneity (within study sites and countries) in malaria transmission intensity, mixed-effects models will include study site as a random effect and associated cluster-robust SEs will be reported where appropriate.

Missing data

The extent and patterns of missing data will be examined for all variables. Reasons for missingness will be documented whenever available. If the proportion of missing data is minimal (<5%, which is lower than the attrition rate of 10%), complete-case analyses will be performed. For variables with substantial missingness, multiple imputation will be employed under the assumption that data are missing at random. Sensitivity analyses comparing complete-case and imputed analyses will be undertaken to assess the robustness of results.

Bias and confounding

The funding for this observational study is limited to the SCD population and there are insufficient resources to enrol a comparison group of people without SCD. This precludes comparisons of malaria incidence between children with SCD and those without. The study cohort may not represent all people living with SCD due to enrolment via SPARCo supported healthcare facilities resulting in selection bias. Therefore, random sampling techniques will be employed to invite participants from each site. The self-reporting of medical history may be incomplete resulting in information bias. In addition, there may be inter-site variability that is not accounted for. We will employ standardised data collection protocols across sites and provide rigorous training to study team personnel. Unmeasured or inadequately controlled factors, such as socio-economic status, nutrition or environmental/climate exposures, may confound the association between SCD and malaria exposure. We propose the collection of comprehensive data on these potential confounders and use statistical methods, such as multivariable regression analysis, to adjust for confounding variables as well as stratifying analyses by relevant covariates to assess their impact on study outcomes.

Ethics and dissemination

Ethical review and approvals

Ethical approval has been obtained in Ghana (KATH IRB/AP/046/25), Mali (2024/274/CE/USTTB), Nigeria (NHREC/01/01/2007-22/10/2025C), Tanzania (MUHAS-REC-01-2025-2593), Uganda (Mak-SOMREC-2024-1091), Zimbabwe (MRCZ/A/3292) and Zambia (NHRA-1916/03/02/2025). The full names of the ethics committees are as follows. Ghana: Komfo Anokye Teaching Hospital Institutional Review Board; Mali: Ethics Committee of the University of Sciences, Techniques and Technologies of Bamako; Nigeria: National Health Research Ethics Committee of Nigeria; Tanzania: Muhimbili University of Health and Allied Sciences Research Ethics Committee and National Health Research Ethics Committee; Uganda: Makerere School of Medicine Research and Ethics Committee; Zambia: National Health Research Authority and Excellence in Research Ethics and Science Converge Institutional Review Board; and Zimbabwe: Joint Research Ethics Committee and the Medical Research Council of Zimbabwe.

The site-specific Institutional and National Research Ethics Committees approved the protocol, the informed consent document, patient recruitment brochures and any subsequent modifications. A copy of the approved clinical protocol is available as a online supplemental file.

Informed consent and assent

Before participant enrolment is begun, the study team will engage in discussion with the local patient community. The PI or a trained research assistant will obtain informed consent from participants, and assent will be sought from minors or individuals unable to provide full consent, as appropriate.

The information provided will include the study’s summary, implications, constraints and any potential risks. Participation is voluntary and participants are free to withdraw at any time without affecting the care or treatment provided at the sickle cell clinic. The participant and their parent/caretaker will be given sufficient time to consider the information and will have the opportunity to ask the investigator or other impartial, independent parties any questions before deciding whether to participate in the study. The consent form will be provided in a local language that is understandable to both the parent/caretaker and the participant. Written informed consent and assent will be obtained, including the participant and parent/caretaker’s name, dated signature or thumbprint (if unable to write) and the dated signature of the person who presented and obtained the consent and assent.

Declaration of Helsinki

The investigators will conduct this study in compliance with the current revision of the Declaration of Helsinki.

International Council for Harmonisation Good Clinical Practice guidelines

The investigators will ensure that this study is conducted according to the participating countries’ national regulations and that it will follow the principles of Good Clinical Practice established by the International Council for Harmonisation.

Confidentiality

To maintain subject confidentiality, all laboratory specimens, evaluation forms, reports and other records will be identified by a coded number. Only research personnel will have access to participant records. The site investigators and staff can share clinical information for patient care reasons, for example, local consultations.

Risks

The risk of participation is minimal and limited to the pain and bruising that may happen during the sample collection. We shall use experienced phlebotomists to draw blood and aseptic measures to minimise the risk of infections. In the event of any severe adverse events, participants will be treated at the site or referred to the local referral hospital, where the best available care will be provided.

Benefits

There is no direct benefit to the patient, but the knowledge gained from this study will be of greater benefit to all patients with SCD as it will inform our understanding of the epidemiology of malaria in people with SCD in Africa.

Dissemination plans

The study results will be published and disseminated at national and international conferences and in open-access peer-reviewed scientific journals. Any data published will protect the participants’ identities. This study will be registered in a web-based protocol registration scheme. A final report will also be submitted to the US National Institutes of Health and the Ministry of Health of each participating country.

This study will provide robust evidence on the burden of malaria in the SCD population, highlighting the unique and disproportionate risks faced by this vulnerable group. By identifying key factors that contribute to the elevated malaria morbidity among patients with SCD, the findings will inform the development of targeted, evidence-based malaria prevention strategies. These strategies are expected to improve clinical outcomes for individuals with SCD and contribute to broader public health efforts aimed at reducing malaria-related morbidity in high-risk populations. Moreover, this study will lay a strong foundation for future implementation research, facilitating the translation of these preventive measures into practice and ultimately reducing both malaria morbidity and mortality in patients with SCD.

Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.