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Kwambele et al
ISSN:2579-079X
IDOSRJOURNAL OF SCIENCE ANDTECHNOLOGY8(1):60-67, 2022. Prevalence of AKI among Children with Severe Malaria at Kiryandongo General Hospital, Uganda
Department of PaediatricsandChild Health of Kampala International University, Uganda.
ABSTRACT
Malaria remains one of the leading health problems of the developing world, and acute kidney injury (AKI) is a well-recognized complication of severe malaria in adults; but the clinical importance of AKI in pediatric severe malaria is not well documented. Knowledge of the prevalence, outcomes and factors associated among children with severe malaria is the mainstaystrategy,whichcanhelpto reduce the burdenofAKIamong thisvulnerablegroup. A hospital based prospective cohort and analytic study of children with severe malaria was carried out at Kiryandongo General Hospital. The study involved 350 children with severe malaria attending the study site from August to October 2021. Questionnaires were administered to caretakers to obtain socio-demographic. Medical data was obtained by carrying out a through physical examination followed by laboratory tests. Blood samples weretestedforcreatinineandbloodsmearformalaria.Datawereanalyzedusingunivariate, bivariate and multivariate logistic regression analyses to determine the prevalence and factors associated with acute kidney injury among children with severe malaria.The mean ageofchildren withseveremalaria was 7.0±3.8yearsand54.3%ofthemwere male. Of the 350 children enrolled in the study with severe malaria, 167 had AKI, giving an overall AKI prevalence of 47.7% (95% CI: 42.5-53.0).The prevalence of acute kidney injury was high as well as mortality rate of AKI among children with severe malaria still high, in Kiryandongo General Hospital.
Keywords: prevalence, AKI, children, malaria, Uganda
INTRODUCTION
Malariaisalife-threateningdiseasecaused byPlasmodiumspeciesandtransmittedby female Anopheles mosquitoes [1,2,3,4]. In history malaria was taken as a zoonotic disease in the primates of Africa through the 21st century. Malaria is a life threatening human infectious disease, worldwide except Antarctica and the most important factors in the spread or eradication of disease have been human behaviour and living standards. Traditional herbal remedies have been used to treat malaria for thousand years and the bark of cinchona tree which contains quinine have been the first effective treatment for malaria [2,5,6,7] Malaria cases and death in Africa occur in sub-Saharan Africa and children aged less than5yearsarethemostvulnerablegroup affected by malaria. In 2018, they accounted for 67% of all malaria deaths
worldwide [3,8,9,10,11,12]. Persistence of malariainAfricaisduetoacombinationof factors such as a very high transmission secondary to the mosquito Anopheles Gambiae complex. Plasmodiumfalciparum is the predominant parasite which is the species that is the most likely to cause severe malariaanddeath [13,14,15,16,17] The local weather conditions are favourable for the development and transmission of the Plasmodium species and the scarcity of resources and socioeconomic instability have hindered efficient malaria control activity [4,18,19,20,21] According to the latest World malaria report, released in November 2018, there were 219 million casesofmalariain2017andtheestimated number of malaria deaths stood at 435,000, a similar number to the previous year and four African countries accounted
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for nearly half of all malaria cases worldwide. The four countries were Nigeria (25%), the Democratic Republic of the Congo (11%), Mozambique (5%) and Uganda (4%).
Malaria was the first parasitic infection to be clearly associated with glomerular diseases in tropical areas. Severe malaria can cause disease in glomeruli, tubules and in the interstitial region and, therefore, AKI is a known complication of malaria and can occur in around 40% of
Study design
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patients with severe disease caused by P. falciparum in endemic regions, contributing to high mortality rate of around 75% when renal replacement therapy is not started in time [5]. In this study, the association between severe malaria and AKI was determined among childrenwhoarelivinginahighlyendemic regionofmalariainUganda.Thestudywas done to determine the prevalence of acute kidney injury among children with severe malaria at Kiryandongo General Hospital.
METHODOLOGY
Thiswasaprospectivecohortandanalytic study to determine the outcomes and describe factors associated with AKI among children with severe malaria at Kiryandongo General Hospital. At baseline children with severe malaria were investigated to determine the proportion ofchildrenwithAKI. ThechildrenwithAKI among those with severe malaria were followed up to discharge. The outcome was determined in terms of death and survival.
Study site
The study was conducted at Kiryandongo General Hospital which is located in Kikube Parish, Kiryandongo sub-county, Kibanda County, in Kiryandongo District, about 50 kilometers (31 miles), north-east of Masindi General Hospital.
Study population
Thestudypopulationincludedallchildren from 2 months to 12 years attending Kiryandongo General Hospital.
Target population
Thetargetpopulationwasallchildrenwith severe malaria, aged from 2 months to 12 years attending Kiryandongo General Hospital. Before the age of 2 months, malaria is rare.
Inclusion criteria
Achildwasincludedinthestudyifhe/she was aged 2 months to 12 years and admitted with severe malaria after obtaining informed consent from caretaker and assent from children above 8 years.
Exclusion criteria
Achildwasexcludedfromparticipationin the study if he/she has any of the following: Children with, malnutrition,
pre-existing kidney diseases and conditions that cause chronic kidney injury such as hypertension, sickle cell disease andchronic glomerulonephritis. Sample size determination
Sample size for the prevalence of AKI in children with severe malaria was calculated by the use of [6] as shown below: n=[Z²p (1-p)]/e² where: n:desiredsample size Z: standard deviation taken as 1.96 at a confidence interval of 95% p: the prevalence of AKI among children with severe malaria in Uganda (Mulago) was 35.1% [7].
e:the degree ofaccuracy= 0.05. n= [(1.96)²(0.351) (1-0.351) / (0.05)²= 350 children.
Estimating the sample size for factors associated with AKI among children with severe malaria. Using the double proportion formula as shown below: �� = (��1 +��2)22��(1 ��) (��2 ��1)2 Where: �� = (��1+��2) 2
Z1 is Z value at 95% level of significance = 1.96, Z2isZ value at 80% power = 0.84, P1istheproportionofAKIamongchildren with herbal medicine use:54.2 % [8]
P2istheproportionofAKIamongchildren without herbal medicine use: 33.3% [8] n= [(1.96+0.84)²*2(0.435)*(1-0.435)/ (0.330.54)²= 192children.
The large sample size of 350 children was used.
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Sampling technique
Participants were consecutively enrolled until the target number was attained. Study participants were selected as they come to the outpatient and emergency departments. Every patient meeting the selection criteria was eligible to participate.
Informed consent process
Written informed consent was obtained from the mother/guardian of each eligible child after explaining the purpose of the study. The consent forms were in both English and Runyoro, and the participants had the right to decline to participate or withdraw from the study at any time if they so wished. Assent was obtained for children above 8 years of age.
Demographic and clinical information
Following consent, the caretaker was interviewed by the principal investigator. A structured questionnaire was administered by the investigator using English or Runyoro according to the preference of the participant. It was a face to face interview which allowed clarification.Thequestions wereopenand close ended. Variables included sociodemographic,medicalandlaboratory factors. Sociodemographic factors included caretakers’ sociodemographic factors (age and level of education) and child’ssociodemographicfactors(ageand sex). Medical factors included impaired consciousness or unrousable coma, generalizedbodyweakness,prostrationor lethargy:childisunabletofeed,towalkor to sit up without assistance, multiple convulsions:morethan2episodesin24h, respiratory distress (acidotic breathing), clinical jaundice plus evidence of other vital organ dysfunction, dehydration and previous medication. Dehydration was classified as no dehydration, some dehydration and severe dehydration [9]. The laboratory factors included hypoglycemia (blood glucose < 2.2mmol/l or < 40mg/dl, anemia (Hb < 11g/dL), moderate anemia (Hb < 8g/dL), mild (11g/dL), severe anemia (Hb < 5g/dL) (WHO,2014).Hyperparasitaemia(presence of malaria parasites 1-10/single high power field (3+), or >10/ high power field
Kwambele et al(4+) and renal impairment (serum creatinine > 265 micromol/L).
Physical examination findings
The patient history and physical examination were used to gather information. The following were assessed during the general examination: the general condition of the child, jaundice, palor, degree of dehydration, cyanosis, temperature and respiratory rate.
Systemicexaminationincludedrespiratory examination which involved the respiratory rate, oxygen saturation and addedsounds.Theabdominalexamination included the assessement for any organomegaly. The cardiovascular examination included heart rate, heart sounds, added sounds and murmurs. The neurological examination included the evaluation of the level of consciousness.
Laboratory investigations
Full blood count was analyzed using Sysmex Automated Hematology Analyser at Kiryandongo GH. Blood glucose was measured using Freestyle optium glucometerbytheprincipalinvestigatorat admission.Thickbloodsmearsformalaria parasiteswere doneusingFieldstainsA&B and examined by a Laboratory technician using the microscope in the main hospital laboratory. Children with coke coluored urine were assumed to have haemoglobinuria. Serum creatinine was done for the diagnosis of acute kidney injury.
Sample collection procedure
Blood sample was drawn during insertion of intravenous cannula for measurement of full blood count, blood glucose and bloodcreatinine.Priortodrawingofblood, the area was swabbed with cotton dipped in ethyl alcohol 70% to prevent contamination. Five milliliters of blood was drawn for determination of full blood count,bloodglucose andserumcreatinine on admission.the red vacutainer was used to collect 3ml of blood for serum creatinine test and 2ml of blood was collected in the purple vacutainer for CBC and BS test. These laboratory investigations were done on admission in the private laboratory of Kiryandongo Referral Hospital. Severe malaria was confirm by thick field smear of 1-10
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parasites per thick field (+3) or of 10 or more parasites per thickfield(+4). Data processing and analysis plan
Data from completed questionnaires was arranged, summarized and entered into the Microsoft Excel version 2010 and then exported to STATA version 14.2 for analysis. Patient’s baseline characteristics wereanalyzedusingmeansforcontinuous variables with normal distribution and proportions forcategorical variables.
Ethical consideration
Informed consent and respect for participants
Voluntary recruitment was done and an informed consent was signed. Informed consent from the guardians was obtained
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after fully explaining the details of the study to them in English and local languages (Appendices). Assent was obtainedforchildrenabove8yearsofage. Parents were free to withdraw from the study at any time without coercion or compromise of care they were entitled to. Privacy and confidentiality Identification of participants was by means of numerical codes. Details of respondents were kept under lockand key for privacy and confidentiality purposes throughout the course of research. There was no disclosure of participants’ information to the public or any unauthorised person without their consent.
RESULTS
The enrolled children had a mean age of 7.0 years (SD: 3.8), with majority aged between 5 and 12 years (68.9%). There were slightly more males (54.3%) than
females. The mean age of their caretaker was 28.8 years (SD: 7.4) with majority at least 20 years (84.3%), and with primary education (92.3%).
Table 1: Baseline sociodemographic characteristics of study participants (N=350)
Sociodemographic characteristics N = 350
Mean age of child in years (SD) 7.0(3.8) Age of child in years, n (%) 2 months – 5 years 5 years – 12 years 109 (31.1) 241 (68.9)
Sex of child Male Female 190 (54.3) 160 (45.7)
Mean age of caretaker in years (SD) 28.8 (7.4) Age of caretaker in years, n (%) 15 – 19 20 – 24 25 –48
Level of education of caretaker, n (%) No formal education
Primary Secondary
The children had a mean duration of illnessof3.1±0.93daysbeforeadmission withmajorityreportingtohospitalafterat least 3 days of illness (82.0%), with
55 (15.7) 39 (11.2) 256 (73.1)
5(1.4) 323 (92.3) 22 (6.3)
hyperparasitemia (76.3%) and with about half having moderate to severe anemia (51.7%).
Table 2: Baseline medical and laboratory characteristics of study participants (N=350) Medical and Laboratory factors N=350
Mean duration of illness before admission in days (SD) 3.1(0.93) Duration of illness before admission in days n (%) 1- 2 3andabove 63 (18.0) 287 (82.0)
Received aminoglycosides, n (%) No Yes 345(98.57) 5(1.43)
Received NSAIDs, n (%) No Yes 310 (88.6) 40 (11.4)
Hyperparasitemia, n (%) No Yes 83(23.7) 267 (76.3)
Mean hemoglobin level (SD) 9.1(3.36) Hemoglobin/Anemia, n (%) Normal Mild Moderate Severe/life-threatening
125(35.7) 44 (12.6) 28 (8.0) 153 (43.7)
Main symptoms of children with severe malaria at admission The commonest symptoms of children with severe malaria were; convulsions (38.9%), vomiting (35.5%), and diarrhea (19.4%).Figure 1.
40
30
20
Percentage Main complaints
10
38.9 35.5 19.4 2 0.9 0.3 0
50 Convulsions Vomiting Diarrhea Jaundice Loss of consciousness Edema
Figure 1. Main symptoms of children with severe malaria at admission.
The first objective of this study was to determine the prevalence of acute kidney injury among children with severe malaria
at Kiryandongo General Hospital. The results are presentedin Figure 5 .
47.7% 52.3%
Figure 2: Prevalence of acute kidney injury among children with severe malaria
Of the 350 children enrolled in the study withseveremalaria,167hadAKI,givingan overall AKI prevalence of 47.7% (95% CI: 42.5-53.0).Of these, 99 (59.3%), 57 (34.1%) and 11 (6.6%) had grades 1, 2 and 3 AKI respectively.
The prevalence of AKI varied significantly across child age groups (p=0.003) with children <5 years having a higher prevalence (59.6%) as compared to those 5 years and above. No significant gender disparities were noted, p=0.100.
0.003
Child sex specific prevalence Male Female
109 241 65 102 59.6 (50.0-68.5) 42.3 (36.2-48.7)
Table 3: Overall prevalence of AKI with stratification across age and gender categories Prévalence type Total, N Number of children with AKI % (95 % CI) p Overall prévalence 350 167 47.7 (42.5-53.0) Child age specific prevalence 2 mo-<5 5-12
0.100
190 160 83 84 43.7 (36.7-50.9) 52.5 (44.7-60.2)
DISCUSSION
TheprevalenceofAKIamongchildrenwith severemalariainthisstudywas47.7%.The prevalence of AKI was higher compared to the findings of most previous studies. In Uganda two studies have been conducted in Jinja and Mulago by [7; 10] reported an overall prevalence of AKI among children with severe malaria of 45.5% and 35.1% respectively. Similary in a cross sectional study conducted in Nigeria by [11] reported a prevalence of 38%. Through a follow up study conducted in Democratic Republic of Congo, [12] reported a prevalence of 23.6%. The discrepancy could be related to the fact that
Kiryandogo District being one of the high transmission districts with high prevalence of malaria as compared to the low transmission district such as Kampala and Jinja. Kiryandongo has a hot climate which is favorable for the life cycle of the plasmodium and it has the biggest refugee’s camps of the country with low socioeconomic status. Furthermore this study have been conducted in rural area with low socioeconomic status as comparedtourbanarea suchKampalaand Jinja.In addition this current study focus on children age from 2 months to 12years compared to the previous studies that
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involve the age rangefrom6 monthsto 12 years.
CONCLUSION
There is a high prevalence of acute kidney injury among children with severe malaria in Kiryandongo General Gospital. Acute kidney injury among children with severe malaria was associated with low level of
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education of caretakers, young age of children (less than 5 years), history of receiving NSAIDs and anemia (moderate and severe). The mortality rate of children with AKI was high.
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