Prevalence of and factors associated with cerebral malaria among children aged 6 to 59 months with severe malaria in Western Uganda: A hospital-based cross-sectional study

doi:10.21203/rs.3.rs-5057778/v1

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Prevalence of and factors associated with cerebral malaria among children aged 6 to 59 months with severe malaria in Western Uganda: A hospital-based cross-sectional study

https://doi.org/10.21203/rs.3.rs-5057778/v1

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Introduction

Cerebral malaria, caused by Plasmodium falciparum, represents the most severe neurologic complication of malaria. Its association with high morbidity and mortality rates, especially among young children, underscores its clinical significance. In this study, we aimed to determine the prevalence of cerebral malaria and identify associated factors among children admitted with severe malaria at a tertiary hospital in western Uganda.

Methods

This was a cross-sectional, descriptive and analytical study involving children aged 6 to 59 months admitted with severe malaria. The study was conducted from January to March 2023 at Fort Portal Regional Referral Hospital. Severe and cerebral malaria were defined as per the WHO criteria. Sociodemographic, clinical and laboratory data were collected and analyzed using IBM SPSSversion 27. Logistic regression analysis was used to evaluate the factors associated with cerebral malaria. A p value <0.05 indicated statistical significance.

Results

A total of 250 children were recruited (mean age 33.1±17.3 months). The prevalence of cerebral malaria was 12.8% (95% C. I: 8.9-17.6). Cerebral malaria was independently associated with male sex (aOR: 3.05, 95%C. I: 1.20-7.77, p=0.02), abnormal bleeding (aOR: 13.22, 95%C. I: 11.54-15.16, p=0.001), history of convulsions (aOR 12.20, 95% C. I:10.7, -21. 69, p= 0.010), acute kidney injury (aOR: 4.50, 95% C. I: 1.30-15.53, p=0.02), and hyponatremia (aOR: 3.47, 95% C. I: 1.34-8.96, p=0.010).

Conclusions and recommendations

The prevalence of cerebral malaria was high among children with severe malaria. Male sex, a history of convulsion, abnormal bleeding, acute kidney injury, and hyponatremia were associated with increased odds of cerebral malaria. These characteristics should be properly investigated and adequately treated in young children to reduce the risk and complications associated with cerebral malaria.

Infectious Diseases

cerebral malaria

associated factors

under-five

Uganda.

Malaria remains one of the most common and pernicious infectious diseases, despite being entirely preventable and treatable. Children under the age of 5 are particularly vulnerable and accounted for 67% of all malaria-related mortalities in 2019[1]. In 2017, a staggering 87.6% of malaria fatalities occurred in sub-Saharan Africa [2]. However, this mortality is even greater among children under the age of five, reaching 18.1%. Uganda bears the third-highest global burden of malaria, with an overall mortality rate of 13.3%. [1] [3]. Along with other common malaria syndromes, such as severe malarial anemia and respiratory distress (metabolic acidosis), cerebral malaria (CM) accounts for the majority of malaria-related deaths in African children [4]. Cerebral malaria (CM), primarily caused by Plasmodium falciparum, represents the most severe neurologic complication of malaria[5]. It is associated with high morbidity and mortality rates, particularly among young children [6]. A study conducted in Eastern Uganda by Olupot-Olupot et al.[7]reported an overall in-hospital mortality rate of 9.5% among children admitted with severe malaria, with cerebral malaria being the leading cause of death. In addition to the high mortality rate, cerebral malaria is responsible for serious neurological complications and other mental health issues, presumably as a result of ischemic neuronal damage [8][9]. In addition, CM increases the risk of post-discharge hospitalizations related to malaria and other conditions [10].

Although a large number of studies have identified a wide variety of risk factors associated with severe malaria in children [11], few studies have evaluated the predictors of CM in young children in sub-Saharan Africa, Uganda. This study aimed to determine the prevalence and factors associated with cerebral malaria among children aged 6 to 59 months who presented with severe malaria.

Study design, setting, and period

This was a descriptive and analytical hospital-based cross-sectional study. A quantitative approach was used to determine the prevalence and factors associated with cerebral malaria among hospitalized children aged 6 to 59 months with severe malaria in the pediatric ward and high dependent unit (HDU) of Fort Portal Regional Referral Hospital (FPRRH), located in the western Uganda region. According to the last report of the Ministry of Health, this region comprises 9 districts and is described as a moderate-to-high transmission area of malaria[12] [13]. FPRRH is a public regional referral facility under the Ministry of Health and serves as a Teaching Hospital affiliated with Kampala International University. The FRRH has a department of pediatrics and child health, offering a range of specialized services, including the pediatric ward and HDU, from which participants in this study were recruited. The pediatric ward has a capacity of seventy-five beds and is run by four pediatricians, three senior housing officers, and seven nurses. In this facility, which is also a regional referral hospital in Uganda, malaria is treated according to the World Health Organization (WHO) guidelines for managing malaria cases. The data were collected between January and March 2023.

Study population

During the study period, all patients aged 6 to 59 months who were admitted to the pediatric ward and high-dependence unit of Fort Portal Regional Referral Hospital with severe malaria were considered eligible for inclusion.

Selection criteria

This study included all children aged 6 to 59 months who were admitted with severe malaria as defined per the WHO criteria[14]. The same criteria were applied for identifying children with CM. Patients with conditions such as meningitis, encephalitis, epilepsy or cerebral vascular accidents in sickle cell disease were excluded from the study.

Sample size determination and sampling technique

The sample size was calculated using the modified Daniel formula (1999):

where n = minimum sample size, Z₁ = Z value at 95% level of significance = 1.96, Z₂ = Z value at 80% power = 0.84, and R = odds ratio for cerebral malaria according to associated factors. A sample of 225 participants was obtained based on the assumption that the proportion of children with cerebral malaria who did not use mosquito nets was 68.8% versus 31.2% (OR 3) of those who used mosquito nets [15]. To account for nonresponsive and unfinished questionnaires, 10% (25 participants) were added to the sample. Therefore, the overall sample included 250 study participants. Participants who met the eligibility criteria were consecutively enrolled until the required sample size was reached.

Data collection procedures

All patients admitted to the Pediatrics ward and high dependent unit (HDU) of the Fort portal RRH were screened for severe malaria according to the WHO criteria. Cerebral malaria was defined as clinical syndrome characterized by coma ≥ 1 hour after termination of a seizure or correction of hypoglycemia in the presence of asexual Plasmodium falciparum parasites on peripheral blood smears and no other cause to explain the coma. Patients were assessed for the following clinical findings: severe pallor; convulsions; prostration, which was defined as the inability of children older than nine months to sit alone or to drink or breastfeed; and impaired consciousness, defined by a Blantyre coma score ≤ 2 in children. Clinically, shock was defined as cold extremities with a capillary refill > 3 seconds and a weak, fast pulse. Respiratory distress (acidotic breathing) was defined as deep, noisy, frequently fast breathing with increased inspiratory and expiratory chest exertion[4]. Jaundice, the yellowish discoloration of the skin and mucosal surfaces, was assessed clinically by checking the mucosal surfaces of the mouth and/or the sclera. Hemoglobinuria was diagnosed clinically in any child with a history of passage of dark-brown, tea-colored or Coca-Cola urine (according to a score of 5 or more on the Hillman urine color scale) during the present episode of illness observed by the caregiver and where possible by the study clinician. Abnormal bleeding was defined as spontaneous bleeding (defined as physically un-induced and irrepressible bleeding from at least two no traumatized sites in a patient with severe malaria without a previous history of abnormal bleeding). After identifying the study participants, clear explanations of the study procedures were given to them using straightforward language. Subsequently, we obtained informed consent from those willing to participate. After completing the physical examination, 4 ml of blood was collected from each study participant, and the complete blood count (CBC), renal function test and serum electrolytes were studied. A peripheral thick blood smear was performed from a finger prick capillary blood sample. Laboratory factors, including malaria hyperparasitaemia, anemia, thrombocytopenia, acute kidney injury, hemoglobinuria, electrolyte imbalances (sodium and potassium) and hypoglycemia, were evaluated. In patients with a clinical suspicion of meningitis, a lumber puncture was performed to exclude meningitis or other central nervous system infections. All our study participants were treated according to the World Health Organization (WHO) and Uganda National Malaria Control Program guidelines[16].

Data collection instruments

A questionnaire was used to collect sociodemographic information such as age and sex, age of the child, education level, occupation, residence, estimated monthly income of the parent or legal guardian and number of living children. The questionnaire also included information regarding health-seeking behaviors, including herbal medicine use, self-medication, and the time needed to seek health care facilities (delay in seeking health was considered when the time to arrive at the health facility exceeded 24 hours after the onset of the illness). Malaria prevention practices, such as using insecticide-treated mosquito nets and controlling stagnant water around houses, were also considered in the questionnaire. The survey also included data related to medical factors such as duration of illness and immunization status. The nutritional status was also assessed using a UNICEF-designed, no stretchable MUAC, infantometer, stadiometer and weight scale [3]. A 5 ml syringe was used to draw blood. The blood was subsequently transported through a purple top vacutainer containing Ethylenediaminetetraacetic acid (EDTA) and a red top vacutainer without any additives. The complete blood count was analyzed using a Sysmex automated hematology analyzer; renal function tests and serum electrolytes were analyzed using COBAS C311 S/N 1206/13 equipment. Blood sugar was measured using an “on call plus” glucometer.

Malaria testing

The diagnosis of malaria was established through microscopic analysis. Initially, thick blood smears were prepared from capillary blood obtained via finger prick. Microscopic examination was conducted at magnifications of x400 and x1000 to determine the presence of Plasmodium parasites. For the quantification of parasitemia, the parasites observed were counted against a backdrop of 500 white blood cells (WBCs) under the x100 objective. Malaria hyperpasitemia was defined as >100,000 parasites/microliter.

Quality assurance

All the questionnaires were pretested at Fort Portal Regional Referral Hospital before the data collection commenced. Interviews were conducted in Rutooro, a language well understood by the study participants. All the instruments used in the study were calibrated and validated daily. The principal investigator continuously crosschecked the questionnaires, correcting errors during the data collection. Research assistants were adequately trained and routinely supervised by the principal investigator to ensure the correct use of the data tools and adherence to ethical principles. Blood smears were read by two laboratory technicians who were trained and validated by the Ministry of Health for reading blood smear slides.

Data analysis

The data were entered into Epi-Data version 3.1 and exported to Windows’s Statistical Package for Social Sciences (SPSS) version 27 (Armonk. NY: IBM Corp) for all analyses. The prevalence of cerebral malaria was computed as the percentage of participants who had cerebral malaria relative to all participants with severe malaria. Logistic multivariate regression analysis was used to evaluate the associations between independent factors and cerebral malaria Multivariate analysis was performed if a variable had a p value ≤0.2 in the bivariate model. Both the crude and adjusted odds ratios with accompanying confidence intervals were reported. At the multivariate level, a p value ≤0.05 was considered to indicate statistical significance.

Ethical considerations and consent

All procedures were implemented in strict adherence to the applicable national and international guidelines and regulations. Ethical approval was granted by the institutional Research and Ethics Committee of Kampala International University (Reference No: KIU- 2022-218). The FPRRH management authorized the study to take place in the facility. Informed written consent was obtained from all parents or legal guardians.

Baseline demographic and socioeconomic characteristics of the study participants

The mean age of the study participants was 33.1±17.3 months. The highest proportion of children (31.2%) were aged 48 to 59 months, and male and female participants were equally enrolled (50.8% vs 49.2%). Most parents/caretakers had attained a primary education (101/250, 40.4%) and earned a monthly income of less than 200,000 UGX (162/250, 64.8%). The majority of caregivers were married (192/250, 76.8%), and nearly two-thirds (66%) of the households had less than five children. Other demographic and socioeconomic characteristics are presented in Table 1.

Table 1: Demographic and socioeconomic characteristic of study participants
Variables	Frequency	Percent
Sex
Male	127	50.8
Female	123	49.2
Age of children (months)
<12	41	16.4
12-23	38	15.2
24-35	43	17.2
36-47	50	20.0
48-59	78	31.2
Age of caretakers (years)
16-25	78	31.2
26-35	105	42.0
36-45	57	22.8
46-55	10	4.0
Number of children per household
<5	165	66
≥5	85	34
Marital status
Single	58	23.2
Married	192	76.8
Education
Non formal	73	29.2
Primary	101	40.4
Secondary	71	28.4
Tertiary	5	2
Occupation
Non formal	224	89.6
Formal	26	10.4
Religion
Christians	226	90.4
Muslim	16	6.4
Others	8	3.2
Monthly income (UGX)
<200K	162	64.8
≥200K	88	35.2
UGX=Ugandan shilling

Health-related behavior and malaria prevention practices of the study participants.

Most caretakers reported self-medication (174/250, 69.6%), and the majority of patients delayed arriving at the hospital after the onset of illness (239/250, 95.6%). The use of insecticide-treated bed nets was reported by 67.6% (169/250) of the study participants. The other health-related characteristics and malarial prevention practices of the study participants are presented in Table 3.

Table 2: Health-related behavior and malarial prevention practices of study participants
Variables	Frequency	Percent
Use of herbal medicine
Yes	97	38.8
No	153	61.2
Self-medication
Yes	174	69.6
No	76	30.4
Delay in seeking health facility
Yes	239	95.6
No	11	4.4
Use of mosquito net
Yes	169	67.6
No	81	32.4
Presence of stagnant water
Yes	140	56
No	110	44

Clinical and laboratory characteristics of severe malaria among study participants

Approximately one-third of participants had a history of convulsions (82/250, 32.8%) and presented with hemoglobinuria (83/250, 33.2%). Most of the study participants had prostration (189/250, 75.6%). Hyperparasitemia (204/250, 81.6%), thrombocytopenia (110/250, 44%), and severe anemia (80/250, 32%) were the most common laboratory findings (Table 3).

Table 3: Clinical and laboratory characteristics of children aged 6-59 months with severe malaria
Variables	Frequency	Percent
History of convulsion
Yes	82	32.8
No	168	67.2
Hemoglobinuria
Yes	83	33.2
No	167	66.8
Shock
Yes	6	2.4
No	244	97.6
Jaundice
Yes	44	17.6
No	206	82.4
Abnormal bleeding
Yes	7	2.8
No	243	97.2
Hyperparasitemia
Yes	204	81.6
No	46	18.4
Hypoglycemia
Yes	57	22.8
No	193	77.2
Hemoglobin level (g/dl)
Severe anemia (<5)	80	32
Moderate anemia (5-8)	72	28.8
Mild anemia (9-11)	82	32.8
No anemia (>11)	16	6.4
Thrombocytopenia
Yes	110	44
No	140	56
Acute kidney injury
Yes	48	19.2
No	202	80.8
Hyponatremia
Yes	68	27.2
No	182	78.8
Hypernatremia
Yes	8	3.2
No	242	96.8
Hypokalemia
Yes	44	17.6
No	206	82.4
Hyperkaliemia
Yes	25	10
No	225	90

Prevalence of cerebral malaria

The prevalence of cerebral malaria among children aged 6 to 59 months with severe malaria was 12.8% (32/250, 95% CI=8.9%-17.6%).

Factors associated with cerebral malaria

Based on the results of bivariate and multivariate analyses (Table 4), the following factors were significantly and independently associated with cerebral malaria. The likelihood of cerebral malaria was 3.05 times greater in males than in females (95% C. I: 1.20-7.77, p=0.020). The odds of cerebral malaria were 12.20 times greater among children with a history of convulsion than among those without convulsions (95% C. I: 10.7-21.69, p=0.030). There were 13.22 abnormal bleeding events (95% C. I: 11.54-15.16) more likely to have cerebral malaria than did those without abnormal bleeding. There were 4.50-fold greater incidences of acute kidney injury and hyponatremia (95% C. I: 1.30-15.53, p=0.020) and 3.47 times (95% C. I: 1.34-8.96, p=0.010) more likely to develop cerebral malaria than other children.

Table 4. Factors associated with cerebral malaria among children aged 6 to 59 months with severe malaria

Variables	Cerebral malaria		cOR (95% C.I)	aOR (95% C.I)
Variables	Yes (%)	No (%)	cOR (95% C.I)	aOR (95% C.I)
Sex
Male	23(71.9)	104(47.7)	2.80(1.40-6.33)	3.05(1.20,7.77) *
Female	9(28.1)	114(52.3)	1	1
History of convulsion
Yes	30(93.8)	52(23.9)	17.88(11.07-20.71)	12.20(10.7,21. 69) *
No	2(6.2)	166(76.1)	1	1
Hemoglobinuria
Yes	7(21.8)	76(34.9)	1.91(0.79-4.62)	0.20(0.05,1.81)
No	25(78.2)	142(65.1)	1	1
Abnormal bleeding
Yes	4(12.5)	3(1.4)	10.24(2.18-28.13)	13.22(11.54,15.16) *
No	28(87.5)	215(98.6)	1	1
Hyperparasitemia
Yes	29(90.7)	175(80.2)	2.38(0.69-8.16)	2.56(0.60,11.01)
No	3(9.3)	43(19.8)	1	1
Acute kidney injury
Yes	10(31.2)	38(17.4)	2.15(0.94-4.91)	4.50(1.30,15.53) *
No	22(68.8)	180(82.6)	1	1
Hyponatremia
Yes	19(59.3)	49(22.4)	3.71(1.73-7.95)	3.47(1.34,8.96) *
No	13(40.7)	167(76.6)	1	1

aOR=adjusted odds ratio; cOR=crude odds ratio; CI=confidence interval; *Statistically significant (p<0.05)

The prevalence of cerebral malaria was 12.8% (32/250, 95% CI=8.9%-17.6%). This prevalence is higher than that reported in Eastern Uganda (1.4%) by Olupot-Olupot et al. in 2020 [7]. This difference was due to the different study populations. Olupot-Olupot et al. included children aged between 2 months and 12 years. Studies have demonstrated that malaria is less common among infants younger than 6 months old[17][18], while those older than five years have a low risk of severe disease[7]. On the other hand, our findings are comparable to those of other studies conducted in East Africa and other sub-Saharan countries, where the prevalence of cerebral malaria varies between 9.2% and 16.6%[19],[20],[21]. In contrast, the prevalence reported in this study was lower than that reported in studies conducted in Ghana [22], the Democratic Republic of Congo [23] [24], and Gabon [25], where the prevalence was 23%, 30.1% to 48.4%, and 75.4%, respectively. Differences in prevalence may be related to variations in the sociodemographic characteristics of the study participants, such as age [7][23], and variations in the criteria for the diagnosis of cerebral malaria[25]. The current study used the WHO definition of cerebral malaria[4] and was less likely to include patients in a postictal state or with other metabolic complications; however, all the above studies defined CM as children whose comatose state progressed in less than 30 minutes and/or had at least two episodes of generalized seizure within 24 hours and/or who were in a convulsive status. This last definition may include more patients than the one we used.

Factors that were independently associated with cerebral malaria among children with severe malaria were male sex, abnormal bleeding, history of convulsions, acute kidney injury, and hyponatremia.

In this study, male and female participants were almost equally represented (50.8% male vs. 49.2% female). However, being male was associated with a 3.05-fold increase in the odds of developing cerebral malaria (CM) compared to being female. The relationship between CM and male sex in children has yielded mixed results in various studies. Some research has suggested that boys may be at a slightly greater risk of severe malaria, including CM, potentially due to differences in immune responses, genetic factors, or exposure risks[18]. Conversely, other studies have found no significant association between sex and the incidence of cerebral malaria.[26],[27] The current evidence remains inconclusive, highlighting the need for further research to comprehensively understand the sex-specific risks and underlying mechanisms associated with cerebral malaria.

Children presenting with abnormal bleeding exhibited a 13.22-fold increased risk of developing cerebral malaria. The reported incidence of bleeding in severe malaria patients varies considerably from less than 10% to 25%[29]. Although overt bleeding is rarely reported in the pediatric population, it occurs in approximately 5% of children with cerebral malaria and most commonly from the gastrointestinal tract[29],[30]. Cerebral malaria is a multisystemic pathology, and organ damage could explain bleeding disorders associated with cerebral malaria [31]. Blood coagulation activation frequently occurs in patients with severe malaria, and clinically apparent bleeding or disseminated intravascular coagulation is associated with very severe diseases such as cerebral malaria [30]. Bleeding abnormalities and coagulopathy have been reported among patients with non-neurologic complications and concurrent manifestations of cerebral malaria[31]. While gross hemorrhagic or thrombotic events are uncommon in cerebral malaria, their occurrence highlights a clear interaction between P. falciparum infection and coagulation [32],[33]. This finding highlights the importance of recognizing abnormal bleeding as a potential indicator of cerebral malaria in children under the age of five.

Children with convulsions were 12.20 times more likely to have cerebral malaria. These findings were in agreement with previous studies reporting a correlation between multiple convulsions at admission and the occurrence of cerebral malaria [8]. In Ugandan children, a history of convulsions was an independent risk factor associated with impairment of consciousness in children with severe malaria[25],[34],[35],[36]. Convulsions in the presence of malaria are more frequently a sign of cerebral dysfunction than just being febrile fits [37]. The causes of seizures are unclear; most are not associated with fever[38] or electrolyte disorders[39]. Several studies have suggested that ischemia and hypoxia may play a part in this process and that seizures might be caused by sequestration of infected erythrocytes or parasite-derived toxins [40]. Furthermore, immune mechanisms may be important because children with severe malaria and seizures have high titers of antibodies to voltage-gated calcium channels [41].

In the present study, children with acute kidney injury (AKI) exhibited a 4.5-fold increased likelihood of developing cerebral malaria compared to those with normal renal function. This result is in agreement with the findings of a cohort study conducted in Ugandan children aged between 18 months and 12 years evaluating cerebrospinal fluid biomarkers for kidney-brain axis involvement in cerebral malaria pathogenesis, where 46.3% of those with cerebral malaria also had acute kidney injury [35]. In a retrospective case‒control observational study conducted in Zambia involving children aged between 2 and 11 years with central nervous system malaria, 134 out of 209 (64.1%) study participants had AKI according to the KDIGO criteria [42]. In a prospective cohort study in India, cerebral malaria was found to be an important risk factor for mortality in malarial AKI patients [43]. Cerebral malaria occurs as a multisystemic pathology [31]. In Ugandan children, multi-organ dysfunction was common, with 76.2% of children having at least one organ system affected in addition to coma [35]. Cerebral malaria and AKI arise due to vesicular damage resulting from immunological reactions [28]. In patients with cerebral malaria, kidney dysfunction and acidosis are independent predictors of mortality, both in children and adults [44]. The pathogenic mechanisms of AKI in cerebral malaria have not yet been fully defined but include parasite sequestration, endothelial dysfunction, oxidative stress, and immune-mediated damage[42]. In children with cerebral malaria, there is evidence of kidney-brain injury, and multiple potential pathways have been identified[35].

Children with hyponatremia were 3.47 times more likely to have cerebral malaria. Other studies have reported that more than half of patients with CM also experience hyponatremia[36],[45]. The pathophysiology of hyponatremia in cerebral malaria remains unclear, but several studies have suggested that increased secretion of vasopressin plays an important role [46]. Hyponatremia in cerebral malaria may also result from mechanisms such as syndrome caused by inappropriate antidiuretic hormone secretion, cerebral salt wasting, or gastrointestinal and renal losses [47]. A high ADH concentration might be a marker of a decrease in the effective plasma volume, suggesting TNF-alpha-induced endothelial damage and leakage [48]. However, dehydration, more than SIADH, was suggested to be the cause of hyponatremia in severe childhood malaria [39].

To the best of our knowledge, this is the first study to assess the factors associated with cerebral malaria among children in Uganda. This study has several limitations. As a hospital-based cross-sectional study, a causal association could not be established. The study was also limited to one hospital in western Uganda, which precludes the generalizability of our findings.

The present study reported a high prevalence of cerebral malaria among children with severe malaria. Factors associated with cerebral malaria were male sex, a history of convulsions, and other features of severe malaria, such as abnormal bleeding, acute kidney injury, and hyponatremia. Clinical and laboratory manifestations of severe malaria should be promptly investigated and adequately treated to reduce the risk of cerebral malaria in young children.

aOR: adjusted odd ratio

ADH: antidiuretic hormone

AKI: Acute kidney injury

CI: confidence interval

cOR: crude odd ratio

CBC: complete blood count

CM: cerebral malaria

DRC: Democratic Republic of Congo

FPRRH: Fort Portal Regional Referral Hospital

HDU: High-Dependent Unit

KDIGO: Kidney Disease Improving Global Outcomes

KIU: Kampala International University

IBM SPSS: Statistical Package for the Social Sciences

MUAC: mid-upper arm circumference

TNF: tumor necrosis factor

SIADH: Syndrome of Inappropriate Antidiuretic Hormone Secretion

UGX: Uganda shillings

UNICEF: United Nations International Children’s Emergency Fund

WHO: World Health Organization

Acknowledgments

We thank all participants for their contributions to this study and the nursing team of FPRRH for the assistance provided during the data collection.

Funding

This research received no external funding.

Authors' contributions

BM was the principal investigator, conceptualized and designed the study, collected the data and wrote the original manuscript. GN, ORJ and MN supervised the writing and revision of the manuscript. BM and PKK analyzed and interpreted the data. WIE, MN, DB and EBT reviewed and improved the manuscript. All the authors approved the final version of the manuscript for publication.

Availability of data and materials

Data is available upon request. Requests should be sent to [email protected] (BM)

Ethics approval

Ethical review and approval were obtained from the Research Ethics Committee of Kampala International University, Western Campus (Ref. KIU-2022-218). Permission to execute the study was sought in advance from the administration of Fort Portal Regional Referral Hospital.

Consent to participate

Written informed consent was obtained from the caregivers of the children. Study participants were free to withdraw from the study at any point without any consequences.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflicts of interest.

Clinical trial number: not applicable

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The authors declare no competing interests.

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Prevalence of and factors associated with cerebral malaria among children aged 6 to 59 months with severe malaria in Western Uganda: A hospital-based cross-sectional study

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Abstract

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Background

Methods

Selection criteria

Sample size determination and sampling technique

Data collection procedures

Malaria testing

Quality assurance

Data analysis

Results

Baseline demographic and socioeconomic characteristics of the study participants

Health-related behavior and malaria prevention practices of the study participants.

Clinical and laboratory characteristics of severe malaria among study participants

Factors associated with cerebral malaria

Discussion

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Funding

Ethics approval

References

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