unconscious, appropriate size Foley’s catheter was used while transparent adhesive urine bag were used for conscious patients. Total urine volume was recorded in milliliters. At the end of the 6 hours, I extrapolated the urine volume per hour by dividing total urine volume obtained over a 6 hour period by 6. The volume per hour was again divided by the weight of the child to get the volume of urine in ml/kg/hr. Volume less than <0.5ml/Kg/hour was taken as oliguria.47 8. Lumbar puncture; For patients with suspected cerebral malaria, lumber puncture test for cerebrospinal fluid(CSF) analysis was done to rule out possible central nervous system infection as a cause of the coma or altered sensorium. This procedure was done under strict sterile condition, with the assistant carefully placing the child in lateral recumbent position and flexing the neck and the legs, a blue needle was carefully advanced between L4-L5 until a pop was felt as the needle penetrates the dura to enter the subarachnoid space. The CSF collected was sent to the laboratory for biochemistry(glucose and protein) and microbiology(microscopy, culture and sensitiviity).
44
ETHICAL APPROVAL
Ethical clearance certificate was obtained from the Ethics Committee of UBTH, Benin City. Informed and written consent was also obtained from each parent(s) (or guardians) of the study subjects. (see appendix III).
45
DATA HANDLING AND ANALYSIS
All clinical and laboratory data collected from each subject in the study was recorded in a standard pro-forma. (see appendix I).
The results were recorded on a spread sheet using Microsoft Excel 2007. Analysis was done using SPSS version 16. Data collected on the study pro-forma were entered using numeric codes. Frequency distribution tables of demographic variables were generated. Measures of central tendency and dispersion for quantitative variables were determined.
The relationship(s) between proportions was assessed using Chi-square or the Fisher’s Exact test where appropriate and the Student t-test was used to test for significance of the difference between categorical variables and continuous variables respectively. The level of significance of each test was set at p<0.05
46 RESULTS
Two hundred and fifty-three children were recruited for the study, but 33 were excluded because their malaria parasite smear were negative. Another 20 children were also excluded because, although they had positive malaria parasite, they did not have clinical features in keeping with severe malaria. Results for 200 children with positive malaria parasitaemia and features of severe malaria were subsequently analyzed. Of the 200, 96 (48.0%) were males while 104 (52%) were females. The mean ± (SD) weight was 11.5 + 1.8kg (range: 8 – 19 kg) while the mean ± (SD) height was 87.6 + 8.7cm (range: 74 - 110 cm). The Mean ± (SD) body surface area was 0.5 + 0.8m2 (range: 0.21 - 0.72 m2). Most children were from the middle social class [89 (44.5%)]; This was followed by the lower social class[64 (32.0%)]; while the least class represented was the upper social class [47(23.5%)]. (see appendix VI for social classification)
47
Depicted in table II is the age distribution and socio-demographic characteristics of the children with severe malaria. The prevalence of severe malaria declined with increase in age.
Table II: Age distribution and socio-demographic characteristics of the study population by gender.
Gender
Age group in months Female (%) (n = 104) Male (%) (n = 96) n=200(%) 12 – 23 38 (19.0) 40 (20.0) 78 (39.0) 24 – 35 41 (20.5) 27 (13.5) 68 (34.0) 36 – 47 17 (8.5) 16 (8.0) 33 (16.5) 48 - 60 08 (4.0) 13 (6.5) 21 (10.5) Social class
Upper 24 (12.0) 23 (11.5) 47 (23.5) Middle 45 (22.5) 44 (22.0) 89 (44.5) Lower 35 (17.5) 29 (14.5) 64 (32.0)
48
Of the children with severe malaria, the symptoms peculiar to those who had ARF(see page 10) as a form of renal function impairment is as displayed in table III. Coma is the only symptom noted that may be significantly associated with ARF. Of the 196 with oliguria, only 5 who had serum creatinine >3mg/dl(see page 52) were diagnosed as having ARF
Table III; Symptoms of children with severe malaria, who had ARF, as a form of renal function impairment.
ARF Yes (%) No (%)
n = 5 n = 195 OR p value
Symptoms Vomiting
Yes 0 (0.0) 77 (39.5)
No 5 (100.0) 118 (60.5) 0.1 0.16
Diarrhoea
Yes 0 (0.0) 32 (16.4)
No 5 (100.0) 163 (83.6) 0.5 1.00
Multiple convulsions
Yes 1 (20.0) 14 (7.2)
No 4 (80.0) 181 (92.8) 3.2 0.33 Altered sensorium
Yes 0 (0.0) 10 (5.2)
No 5 (100.0) 185 (94.8) 1.6 1.00
Coma
Yes 3 (60.0) 13(6.7)
No 2 (40.0) 182(93.3) 21.0 0.004*
Reduced urine output
(Oliguria)
Yes 5 (100.0) 181 (92.8)
No 0 (0.0) 14 (7.2) 1.2 1.00
Fishers exact test used for analysis. * statistically significant
49
The peculiar signs and laboratory features of children with severe malaria, who had ARF(see page 10) as a form of renal function impairment are as shown in table IV. Jaundice and haemoglobinuria occurred significantly in association with ARF. Occurrence of haemoglobinuria and jaundice could be pointer to the presence of ARF
Table IV; Signs and laboratory features of children with severe malaria, who had ARF, as a form of renal function impairment.
ARF
Yes (%) No (%) OR p value n = 5 n = 195
Signs Pallor
Yes 4 (80.0) 107 (54.9)
No 1 (20.0) 88 (45.1) 3.3 0.38
Jaundice
Yes 4 (80.0) 58 (29.7)
No 1 (20.0) 139 (71.3) 10.0 0.03*
Prostration
Yes 0 (0.0) 7 (3.6)
No 5 (100.0) 188 (96.4) 20.3 1.00
Dehydration+
Mild 5 (100.0) 169 (86.7) Moderate 0 (0.0) 6 (3.1)
Severe 0 (0.0) 20 (10.2) + 0.68 Laboratory features
Acidosis
Yes 1 (20.0) 27 (13.8)
No 4 (80.0) 168 (86.2) 1.6 0.53
Haemglobinuria
Yes 4 (80.0) 12 (6.2)
No 1 (20.0) 183 (93.8) 61.0 0.0001*
Fishers’ Exact Test used for analysis * Statistically significant + ; χ2 = 0.8 Displayed in table V are the symptoms of children with severe malaria, who had abnormal eGFR
50
as a form of renal function impairment. Coma and oliguria are the only two features occurring significantly in association with impairment of renal function based on eGFR values.
Table V; Symptoms of children with severe malaria, who had abnormal eGFR, as a form renal function impairment.
Abnormal eGFR Yes (%) No (%)
n =136 n = 64 OR p- value Symptoms
Vomiting +
Yes 53 (39.0) 24 (37.5)
No 83 (61.0) 40 (62.5) 1.0 0.97
Diarrhoea
Yes 23 (17.0) 9 (14.1)
No 113 (83.0) 55 (85.9) 0.8 0.76
Multiple convulsions
Yes 11 (8.1) 4 (6.3)
No 125 (91.9) 60 (93.7) 0.8 0.78
Altered sensorium
Yes 8 (5.9) 2 (3.1)
No 128 (94.1) 62 (96.9) 0.5 0.51
Coma
Yes 15 (11.0) 1 (1.6)
No 121 (99.0) 63 (98.4) 0.1 0.02*
Oliguria
Yes 123 (90.4) 63 (98.4)
No 13 (9.6) 1 (1.6) 0.2 0.04*
+ ; χ2 = 0.0, * statistically significant
In table VI are the signs and laboratory features of children with severe malaria, who had abnormal eGFR as a form of renal function impairment. Pallor, prostration, and dehydration occurred significantly in association with impairment of renal function using eGFR values.
51
Table VI shows signs and laboratory features of children with severe malaria, who had abnormal eGFR, as a form of renal function impairment
Abnormal eGFR
Yes (%) No (%) χ2 OR p value Signs
Pallor
Yes 83 (61.0) 28 (43.7)
No 53 (39.0) 36 (56.3) 4.6 0.5 0.03*
Jaundice
Yes 45 (33.0) 15 (23.3)
No 91 (67.0) 49 (76.7) 1.5 0.6 0.22
Prostration
Yes 5 (3.7) 2 (3.1)
No 131 (96.3) 62 (96.9) x 5.7 0.04*
Dehydration
Mild 121 (89.0) 53 (82.5)
Moderate 6 (4.4) 0 (0.0)
Severe 9 (6.6) 11 (17.5) 7.6 - 0.02*
Laboratory features Acidosis
Yes 23 (17.0) 5 (7.8)
No 113 (83.0) 59 (92.2) 2.3 0.4 0.13
Haemglobinuria
Yes 12 (8.8) 4 (6.3)
No 124 (91.2) 60 (93.7) x 0.7 0.78
x = Fishers’ Exact Test, * = statistically significant Shown in table VII is the spectrum of symptoms and signs in children with severe malaria. All 200 children presented with fever. Other common symptoms included vomiting [77(38.5%] and diarrhoea [32(16.0%)]. Most common sign was pallor [111(55.5%)]. Twenty-six (14.5%)
52
presented with moderate to severe dehydration. Five had serum creatinine levels >3mg/dl Table VII: Spectrum of symptoms, signs and laboratory features in children with severe malaria
Spectrum n=200 (%) Symptoms
Fever 200 (100.0) Reduced urine output (oliguria) 186 (93.0) Vomiting 77 (38.5) Diarrhoea 32 (16.0) Coma 16 (8.0) Coke colored urine 16 (8.0) Seizures 15 (7.5) Altered Sensorium 10 (5.0) Signs
Pallor 111 (55.5) Jaundice 60 (30.0) Dehydration (moderate - severe) 26 (14.5) Prostration 7 (3.5) Laboratory features
Acidosis 28 (14.0) Haemoglobinuria 16 (8.0) Serum creatinine(>3mg/dl) 5 (2.5) Haematuria 4 (2.0)
Table VIII reveals the spectrum of manifestation of severe malaria utilizing WHO criteria. It is observed that substantial number of the patients had severe anaemia [76(38.0%)], jaundice [60(30.0%)] and hyperpyrexia [35(17.5%)]. Hyperparasitaemia was the least manifestation
53
[5(2.5%)]. Other defining criteria are as shown in Table VIII.
Table VIII: Spectrum of manifestation of severe malaria based on WHO severe malaria criteria
Severity criteria n=200 frequency(%)
Severe anemia 76 (38.0)
Jaundice 60 (30.0)
Hyperpyrexia 35 (17.5) Hypoglycaemia 31 (15.5) Acidosis 28 (14.0) Dehydration 26 (13.0) Haemoglobinuria 16 (8.0)
Multiple convulsions 15 (7.5) Cerebral malaria 10 (5.5)
Prostration 7 (3.5) Hyperparasitaemia 5 (2.5) Acute renal failure 5 (2.5) Pulmonary edema 0 (0.0) Spontaneous bleeding. DIC 0 (0.0) Circulatory collapse, shock 0 (0.0)
See appendix ii for diagnosis of cerebral malaria, hyperparasitaemia Prevalence of proteinuria and haematuria
Thirty-five of the 200 children had proteinuria making the prevalence of proteinuria to be 17.5%, while 4 of the 200 children had haematuria giving the prevalence of haematuria as 2.0%.
54
Table IX shows the relationship between gender, age group and incidences of proteinuria/ haematuria. Of the 35 children presenting with proteinuria, 11 were males while 24 were females giving gender prevalence of proteinuria of 31.4% for males and 68.6% for females.
There were significantly more females than males with proteinuria ( χ2 = 4.67; p=0.031).
Haematuria was also significantly more in females. (χ2 =3.77; p = 0.05).
Whereas proteinuria was significantly more among children from low socio-economic class ( χ2 =14.1; p=0.0009), there was no significant association between the prevalence of haematuria and any of the socio-economic class (χ2 = 1.63, p = 0.44).
55
Table IX; Prevalence of proteinuria and haematuria / social class distribution of children with severe malaria
Proteinuria Haematuria
Gender Present (%) Absent (%) Present (%) Absent (%) n = 35 n =16 n = 4 n = 196 Male 11 (31.4) 85 (51.5) 00 (0.0) 96 (49.0)
Female 24 (68.6) 80 (48.5) 04 (100.0) 100 (51.0) χ2 = 4.67, p = 0.031* χ2 = 3.77, p = 0.05
Age Group(months)
12-23 12 (34.3) 66 (40.0) 01 (25.O) 77 (39.3) 24-35 12 (34.3) 56 (33.9) 01 (25.0) 67 (34.2) 36-47 08 (22.9) 25 (15.2) 02 (50.0) 31 (15.8) ≥48 03 (8.5) 18 (10.9) 00 (0.0) 21 (10.7) χ2 = 1.43, p = 0.698 χ2 = 3.51, p = 0.32 Social class
Upper 08 (22.9) 39 (23.6) 02 (50.0) 45 (23.0) Middle 07 (20.0) 82 (49.7) 01 (25.0) 88 (44.9) Lower 20 (57.1) 44 (26.7) 01 (25.0) 63 (32.1) χ2 = 14.11, p = 0.0009* χ2 = 1.63, p = 0.44
* = statistically significant
56
The prevalence of proteinuria by forms of severe malaria in children.
Proteinuria occurred significantly in patients with severe anaemia (p=0.000); occurrence of jaundice (p=0.001), heamoglobinuria (p=0.000), dehydration (p=0.014), hyperparasitaemia (p=0.000), and those with established ARF (p = 0.004).
Table X : Prevalence of proteinuria by forms of severe malaria
Forms of severe malaria Yes No χ2 p-value
Severe anemia (n = 31) 27 (87.1) 04 (12.9) 27.6 0.000*
Jaundice (n = 33) 19 (48.5) 14 (54.5) 11.9 0.001*
Haemoglobinuria (n = 6) 06 (100.0) 00 (0.0 82.0 0.000*
Dehydration (n = 26) 09 (34.6) 17 (65.4) 6.1 0.014*
Hyperpyrexia (n = 25) 06 (24.0) 29 (76.0) 0.0 0.951 Hyperparasitaemia (n = 5) 05 (100.0) 00 (0.0) 24.2 0.000*
Hypoglycaemia (n = 31) 05 (16.1) 26 (83.9) 0.1 0.827 Acute renal failure (n = 5) 04 (80.0) 01 (20.0) + 0.004*
Cerebral malaria (n = 10) 03(30.0) 07 (70.0) 1.1 0.286 Multiple convulsion (n = 15) 03 (20.0) 12 (80.0) 0.1 0.791 + ; OR = 21, * statistically significant
57
The prevalence of haematuria by forms of severe malaria in children
Haematuria occurred significantly only amongst children with haemoglobinuria (p=0.000), jaundice(p=0.047), Acute renal failure(p=0.002), and hyperparasitaemia (p=0.000)
Table XI; The prevalence of haematuria by forms of severe malaria
Haematuria
Forms of severe malaria Yes No χ2 p-value Haemoglobinuria (n = 16) 04 (25.0) 12 (75.0) 46.9 0.000*
Jaundice (n = 60) 03 (5.0) 57 (95.0) 3.9 0.047*
Severe anemia (n = 76) 03 (3.9) 73 (96.4) 2.4 0.124 Acute renal failure (n = 5) 03 (60.0) 02 (40.0) + 0.002*
Cerebral malaria (n = 10) 01 (10.0) 09 (90.0) 3.4 0.064 Dehydration (n = 26) 01 (3.8) 25 (96.2) 0.5 0.471 Hyperparasitaemia (n = 5) 01 (20.0) 04 (80.0) 8.5 0.004*
Hyperpyrexia (n = 35) 01 (2.8) 34 (97.2) 0.6 0.690 Multiple convulsions (n 15) 00 (0.0) 15 (100.0) 0.3 0.565 Hypoglycemia (n = 31) 00 (0.0) 31 (100.0) 0.8 0.387
+ ; OR = 97,
*
statistically significantAs could be observed in table XII, of the 200 children presenting with acute severe malaria, there
58 were more females than males with abnormal GFR.
Table XII: Pattern of eGFR by gender in children aged 12-60 months with severe malaria
GFR(ml/min/1.73m2) Male (%) Female (%)
≥90(normal) n = 64 36 (56.2) 28 (43.8)
< 90(abnormal) n = 136 60 (44.1) 76 (55.9) χ2 = 2.10, OR =- 1.6, p = 0.15
It could be observed that more of the children aged 12-23months (44.9%) had abnormal eGFR.
Overall, the proportion of children with abnormal eGFR (renal function impairment) declined with increasing age
Table XIII: Distribution of eGFR in children aged 12-60 months(1 to 5years) with severe malaria by age
Age (months) 12-23 (%) 24-35 (%) 36-47 (%) ≥48 (%)
eGFR (normal) n=64 17 (26.6) 24 (37.5) 15 (23.4) 08(12.5) eGFR (abnormal) n=136 61 (44.9) 44 (32.3) 18 (13.2) 13 (9.6)
χ2 = 7.18, p = 0.07
59
The distribution of children with renal impairment according to gender, age group and social class
More females had renal impairment than males. However, this gender relationship was not statistically significant (p = 0.11). Nonetheless, renal impairment in severe malaria tended to decline with increase in age. Although not statistically significant, renal impairment as determined by eGFR was common in children drawn from the middle social class.
Table XIV: Distribution of children (according to gender, age group, and social class) with renal function impairment using eGFR values
Renal function impairment using eGFR values
Yes No
Gender n = 136 (%) n = 64(%) χ2 p value Male 60 (44.1) 36 (56.2) 2.6 0.11
Female 76 (55.9) 28 (43.8)
Social class
Upper 27 (19.9) 20 (31.3) 4.6 0.10 Middle 60 (44.1) 29 (45.3)
Lower 49 (36.0) 15 (23.4) Age group
12-13months 61 (44.9) 17 (26.6) 7.2 0.07 24-35months 44 (32.4) 24 (37.5)
36-47months 18 (13.2) 15 (23.4) ≥48months 13 (9.5) 8 (12.5)
60
As shown in table XV, all five (100.0%) children who had acute renal failure were females.
Acute renal failure was commoner in children aged 12-23months and those drawn from the lower social class.
Table XV: Incidence of acute renal failure by gender, age group and social class Gender Acute Renal Failure
Yes No
n = 5 (%) n = 195(%) χ2 OR p value Male 0 (0.0) 96 (49.2) * 0.1 0.06
Female 5 (100.0) 99 (50.8)
Social class
Upper 1 (20.0) 46 (23.6) 1.9 2.0 0.37 Middle 1 (20.0) 88 (45.1)
Lower 3 (60.0) 61 (31.3)
* Fishers exact test used for analysis
DISCUSSION Age group
12-23months 2 (40.0) 76 (40.0) 0.8 3.0 0.86 24-35months 1 (20.0) 67 (34.4)
36-47months 1 (20.0) 32 (16.4)
≥48months 1 (20.0) 20 (10.3)
61
In the index study, it was observed that clinical manifestation of children with renal function impairment(both those that had impaired eGFR and established ARF) occurring in association with severe malaria included vomiting, diarrhea, multiple convulsions, altered sensorium, coma, prostration, oliguria, pallor, jaundice, dehydration, haemoglobinuria and acidosis. These findings are similar to those observed in previous study in the work on quartan malaria nephropathy at Ilorin by Adedoyin and Adeniyi,106 published in 2001. Although previous work at Ibadan in 1993 on renal involvement in acute falciparum malaria by Sowunmi108 reported that no reliable clinical features are specific enough for predicting the development of renal function impairment in children with severe malaria, this present study however noted coma, jaundice and haemoglobinuria occurring sufficiently enough as pointers to the probable existence of ARF in children with severe malaria. The index study also observed that prostration, coma, oliguria, and pallor as signs occurred commonly in association with impairment in eGFR among the study population. Similar association between occurrence of oliguria and presence of ARF in children with malaria was observed in a retrospective study done in Port Harcourt between 1985 and 2003 by Anochie and Eke.22 Dehydration was also a common feature noted among those who had impaired renal function in this study( but it was rarely severe). This finding is also in tandem with previous observation in the work by Weber et al20 in 1999 on renal involvement in Gambia children with severe malaria but the degree of dehydration was not reported in that study.
In the present study, the commonest clinical symptom observed in children with renal function impairment occurring in association with severe malaria was fever (100.0%). It was present in all children in the study population. This is an expected finding as the commonest feature of malaria (severe or not severe) is fever. Predictably, severe malaria would be associated
62
with massive release of cytokines and cyclooxygenase by the host in response to haemolysed parasitized erythrocytes. The cytokines are capable of inducing fever by changing the set point of the thermoregulatory center of the brain.105 The same prevalence rate for fever (100.0%) was also observed in a study done by Nitya and Harikrisha136 in 2001 in India among 60 adults with malaria. The authors did not advance reasons for their observations but same massive release of chemical mediators capable of altering the thermoregulatory system of the brain could also explain the fever.
It was observed in the index study that oliguria occurred more commonly than haemoglobinuria(93.0% and 8.0% respectively) in these children with severe malaria. This observation is in contrast with common view that there is paucity of features referable to the renal system in children with severe malaria, particularly pre-school children.108 In a related study on renal function in acute falciparum malaria by Sowunmi108 at Ibadan in 1996, none of the children recruited into the study had any symptom or sign ascribable to genitourinary system.
Both features were implicated among those with ARI in the study population
Vomiting and diarrhoea were the next commonest presenting symptoms in the study subjects (38.5% and 16.0%% respectively). These symptoms were not found in association with development of renal function impairment in children with severe malaria. They however are constitutional symptoms of most illnesses. The direct assault of the malaria parasite sequestered in the gastrointestinal tract vessels do lead to poor perfusion, interference with absorptive processes and gastric irritation which could cause vomiting and diarrheoa.93,106,109 The ensuing dehydration from the fluid loss accompanied by electrolyte derangement and the concomitant effect of the deranged electrolytes on the chemoreceptor zone could also account for the vomiting.93,109 Furthermore, the increase in intracranial pressure in some of the patients with
63
cerebral malaria may also cause vomiting.105 In another study of 27 children aged 0-5years with severe malaria done at Orissa by Bag and Samal137 and published in 1994, the prevalence rates of vomiting and diarrhoea were observed to be 14.8% each. The authors however did not proffer reasons for the low rates of occurrence of the symptoms.
The prevalence of severe anemia among subjects in the current study is 38.0% and is comparable to the 34.0% observed in the work done by Satpathy and Mohanty138 in 2004 among 242 children in India with severe malaria. The occurrence of severe anemia as observed in this study also did not occur more significantly in children with RFI. Hemolysis of parasitized red blood cells could account mainly for the anaemia.69-73 Other factors known to contribute to severe anemia in malaria include marrow suppression by the parasitized red blood cell and parasite toxins, increased red blood cell sequestration and decreased red blood cell survival.69-73 Also, late presentation to the hospital and poor nutrition during the course of index illness and background poor nutrition due to poverty in our environment may also contribute to the high incidence of anemia in these subjects.63-69 Severe anemia in malaria could also be severe in children with background history of sickle cell anemia, and G6PD enzyme deficiency.
Based on WHO criteria for defining severe malaria; severe anemia, jaundice, metabolic acidosis and hyperpyrexia were the commonest defining criteria for severe malaria prevalent in the study locale. Multiple convulsions (82.2%) and cerebral malaria (52.2%) were observed in 2012 in India by Rajesh and Mishra139 to be the commonest defining criteria for severe malaria but these were less frequently encountered in the current study (7.5% and 5.5% respectively).
Hyperparasitaemia, renal failure and shock were the least of the features that defined severe malaria in the study cohort. The low erythrocyte parasitaemia observed in this study despite the fact that subjects in live malaria endemic area could suggest that other factors such as
64
drugs(traditional and orthodox), G6PD deficiency, urinary tract infection and sepsis may be contributory to development of renal function impairment. The low parasitaemia could also be due to the high level of immunity among the subjects, the ease with which antimalarias are accessed and poor management practices in the study locale. In a study at Ibadan in 1996 by Sowunmi108(though not restricted to 1-5years of age) in which children examined were those that have not taken antimalarias for two weeks before presentation, prevalence rate of hyperparasitaemia was observed to be 37.5% as against 2.5% in this index study.
The present study shows a prevalence rate of 7.5% for repeated generalized seizure.
This is in contrast to what was observed in another study done in 2004 at Berhampur, India, by Satpathy and Mohanty,138 involving individuals with severe falciparum malaria where the prevalence of repeated seizures among the under-fives was observed to be 82.2%. The marked disparity between the prevalence figures in the two studies could be attributed to the fact that more children with cerebral malaria were recruited into that study. Differing genetic predisposition in the subjects in the two studies may explain the varied response of the brain and other system to the presence of severe falciparum disease. Possible causes of repeated generalized seizures in subjects in the index studies are fever,4,105 cerebral hypoxia from severe anemia,4,105 metabolic acidosis,4,105 hypoglycemia,4,105 and cerebral malaria4,105 with its attendant complications like cerebral edema and increase intracranial pressure.4,105
Whereas hyperparasitaemia was the commonest defining criteria in children who had renal function impairment associated with severe malaria in the work of Sowunmi108 in 1996, severe anemia was noted as the commonest defining severity criteria in this work. These high incidence of renal function impairment as noted in these two studies is at variance with what was observed in Odisha, India, where very low rate of 11.0% was reported in children with malaria
65
aged 0–59 months in a study conducted by Rajesh and Soumya139 in 2012. The low prevalence rate as observed by Rajesh and Soumja is probably due to the fact that children in the age bracket of 0-11 months were over represented in their study population as children in this age group are less prone to severe malaria due to presence of maternal antibodies. Also the high prevalence rate observed in the index study as compared to the one at Odisha, India could be attributed to the fact that the index study was carried out in a malaria holoendemic zone where Plasmodium falciparium malaria is predominant.
There were more females (12.0%) than males (5.5%) that presented with proteinuria and all the subjects that had haematuria were females. Both values are very low compared to 67.5%
and 29.8% respectively for proteinuria and haematuria reported in a study carried out in India by Pati and Mishra119 and published in 2010. Two mechanisms possibly play some roles in the pathophysiology of renal damage that bring about leakage of protein and blood in urine; these are glomerulonephritis caused by toxins or free radicals, and damage to the tubular cells possibly caused by ischaemia, or an abnormal cytokine expression leading to tubule-interstitial nephritis.20 In study on proteinuria occurring in other febrile illnesses done in Ghana by Weber,20 the prevalence of proteinuria was higher in children with malaria..
GFR was impaired in 68.0% of the subjects with severe malaria in the index study. A prevalence rate of 45.0% for renal impairment was documented in the work by Sowunmi108 in Ibadan, Nigeria. The higher prevalence of compromised GFR recorded in the index study as compared to Sowunmi’s108 work in Ibadan despite the fact that both studies were carried out in comparable malaria zone, could be due to the fact that this study focused only on children who met the standard criteria for the definition of severe malaria, as against the latter that also recruited children with non severe malaria. Furthermore, Schwartz formula which is less error
66
prone in the determination of GFR was used in this study rather than the method of endogenous creatinine and urine volume collection which was used in the previous study. The increased incidence of impaired GFR could also be due to the fact that the index study concentrated only on the age category of children most vulnerable to severe malaria. Similar high prevalence rate (60.0%) of renal function impairment, compared to the observed in the index study, had previously been documented elsewhere in india.18,19
In the present study, ARF presented in only 2.5% of the study population. ARF noticed in these children could be attributed to possible cortical ischaemia and tubular necrosis from persistent low renal perfusion as a result of hypovolaemia (vomiting, diarrheoa and reduced oral intake) and parasitized systemic vessels causing clogging of renal vasculature. In a retrospective study done by Anochie and Eke22 at Port Harcourt, published 2005 and meant to determine the prevalence of acute renal failure in Nigerian children, a rate of 13.7% was observed. The relatively higher rate could be due to the fact that urine volume of <1mL/kg/hour was used for oliguria and the fact that a wider age group category (0-16years) was covered in their study. In prospective work done at Orissa on children with malaria aged 0-5years by another set of authors (Bag and Samal)137 and published in 1994, the prevalence of ARF(defined by serum creatinine >3mg/dl) was observed to be 3.7%. Another work published in India in 2004 by other authors Satpathy and Mohanty138 recorded 7.7% prevalence rate of ARF in children (1-5years) with severe malaria using the WHO standard definition of ARF as in this index study.
In the present study, it was discovered that in children with severe malaria, more females tended to have renal compromise than their male counterparts (55.9%% vs 44.1% respectively).
The reason for this is not readily apparent. The number of children with abnormal eGFR
67
decreased with increasing age and most of the children with abnormal eGFR were from the middle social class.
All the children with acute renal failure were females and 40% of them were drawn from the age group of 12-23months. Also , 60% of all who had acute renal failure were from the lower social economic class, reinforcing probably contribution of poverty to the health care of children.
68 CONCLUSION
Based on findings of this study, the following conclusions could be made;
1. In children aged 1–5 years with severe malaria, coma, prostration, oliguria, haemoglobinuria, pallor and jaundice occurred commonly in patients with renal function impairment. Their presence therefore may call for greater attention during case management to obviate the risk of renal impairment.
2. The prevalence of proteinuria in children aged 1–5 years with severe malaria is 17.5%
3. Prevalence of haematuria in children aged 1–5 years with severe malaria is 2.0%. This was observed only among females.
4. The prevalence of renal function impairment in children aged 1-5years with severe malaria using eGFR as a standard is high(68%).
5. The prevalence of established acute renal failure in children aged 1-5years with severe malaria is 2.5%, and only children aged 12-23months were involved.
6. Overall, the possibility of renal function impairment should be entertained when
evaluating children aged 1-5years with severe malaria.
69 RECOMMENDATION
In evaluating children aged 1-5 years with severe malaria, one should preempt the possibility of renal function impairment to allow for early diagnosis and treatment.
70
LIMITATIONS OF THE STUDY
1. G6PD assay could not be done to exclude patients with this disease who may also present with