Malaria is classified as either uncomplicated (UM) or severe (SM), but the mechanism underlying the progression from uncomplicated to severe is still unclear. This study aimed to assess haematologic and biochemical parameters as potential prognostic biomarkers for differentiating SM from UM in a Ghanaian population. A descriptive cross-sectional study was conducted to sample 166 participants, comprising 42 healthy controls, 78 uncomplicated malaria cases, and 46 severe malaria cases. Blood samples were analysed for full blood count, liver function test, renal function test, and serum angiopoietins. Statistical analyses were carried out using GraphPad Prism 9 software. Median and interquartile ranges, Mann-Whitney U test, and Kruskal-Wallis analysis were done to compare groups. The haemoglobin and platelet counts of SM patients were significantly lower than those of the UM group (p < 0.05). However, the White Blood Cell (WBC) counts of severe malaria patients (7.4, IQR: 5.4 - 10.6) were significantly higher than the uncomplicated malaria population (5.7, IQR: 5.0 - 6.5) (p < 0.001). Serum levels of bilirubin (total and direct), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total proteins in severe malaria were significantly higher than uncomplicated malaria group (p < 0.001). These findings indicate that haemoglobin, platelet, creatinine, urea, AST, ALT, GGT and bilirubin levels may serve as biomarkers for distinguishing severe from uncomplicated malaria.
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Malaria, caused by Plasmodium species, is classified as uncomplicated or severe
[1]
Cullen, K. A. et al. (2011) ‘Division of parasitic diseases and malaria’, Centre for Global Health, Centres for Disease Control and Prevention (CDC).
[1]
. Based on the severity, the two main types of malaria infection can be differentiated with the aid of a meticulous clinical examination of the patient
[2]
Anvikar, A. R. et al. (2020) ‘Clinical and epidemiological characterisation of severe Plasmodium vivax malaria in Gujarat.
[2]
. Despite several interventions put in place to control malaria, the prevalence of the disease is still a worrying situation among the Ghanaian population
[3]
Diema Konlan, K. et al. (2019) ‘Utilisation of insecticide-treated bed nets (ITNs) among caregivers of children under five years in the Ho municipality’, Interdisciplinary.
[3]
. Although it is estimated that about 250 million cases of malaria occur annually
[4]
Higgins, S. et al. (2016) ‘Dysregulation of angiopoietin 1 plays a mechanistic role in the pathogenesis of cerebral malaria. Science translational medicine,8(358),358ra 128. pp. 1-25. Available at:
, only a small percentage of those progress to severe malaria, which is life-threatening
[5]
Lovegrove, F. E., et al. (2009) ‘Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children’, PLoS ONE, 4(3), pp. 1-8. Available at:
Snow, R. W. et al., (2005) ‘The global distribution of clinical episodes of Plasmodium falciparum malaria’, Nature, 434(7030), pp. 214-217.
[5, 6]
. There is no definitive diagnosis for severe malaria because of its non-specific manifestation coupled with confounders such as diarrhoea in places where the infection is very endemic
[7]
Li, G. et al.,(2020) ‘Distribution of malaria patients seeking care in different types of health facilities during the implementation of National Malaria Elimination Programme’, Malaria journal, 19(1), pp. 1-10.
[7]
. Numerous clinical symptoms, ranging from asymptomatic to varying degrees of fever, are characteristic of defined malaria. Neurological complications and separate or overlapping dysfunction of the cardiovascular, respiratory, hepatic, renal, haematologic, and metabolic systems are all part of the severity of malaria
[8]
Dhangadamajhi, G. et al. (2019) ‘Effect of Plasmodium falciparum infection on blood parameters and their association with clinical severity in adults of Odisha, India’, Acta tropica, 190, pp. 1-8. Perspectives on infectious diseases, 2019.
[8]
.
Prior research on how malaria infections affect blood parameters has shown that the most significant haematological indicators of malaria infection and clinical severity with fatal outcomes are a large drop in platelet counts, anaemia, leucocytosis, or leucopenia
[8]
Dhangadamajhi, G. et al. (2019) ‘Effect of Plasmodium falciparum infection on blood parameters and their association with clinical severity in adults of Odisha, India’, Acta tropica, 190, pp. 1-8. Perspectives on infectious diseases, 2019.
[8]
. On the other hand, a study by
[9]
Muwonge, H. et al.(2013) ‘How reliable are haematological parameters in predicting uncomplicated Plasmodium falciparum malaria in an endemic region?’, International Scholarly Research Notices, 2013(1), p. 673798.
[9]
concluded that haematological alterations are not always accurate laboratory markers of malaria caused by Plasmodium falciparum. But depending on the endemicity, pre-existing hemoglobinopathies, environmental factors, nutritional state, and malaria immunity, these characteristics can change to varying degrees
[10]
Zuberi, U. et al. (2024) ‘Altered haematological parameters in children with malaria infection, a systematic review and meta-analysis’, Diagnostic Microbiology and Infectious Disease, 108(4), p. 116190.
[10]
. The degree to which these haematologic parameters change needs to be looked at.
The number of promising and appealing candidates of prognostic biomarkers that can distinguish between Uncomplicated malaria (UM) and/or severe malaria (SM), including multi-organ dysfunctions in SM, and the steadily worsening circumstance of SM is quite few. The identification of a reliable prognostic biomarker that can accurately and precisely identify people with or at risk of severe malaria would be useful. Therefore, in this study, we sought to assess haematologic and biochemical parameters as prognostic biomarkers for differentiating severe malaria from uncomplicated malaria in a Ghanaian population.
2. Materials and Methods
2.1. Study Population and Design
A cross-sectional study was employed to recruit 166 participants who attended the Seventh Day Adventist Hospital, Bremang, in the Suame Municipality of Ghana. The institution was selected because it serves as the main healthcare provider for most of the population living in the catchment area. The community inhabitants are primarily artisans and industrious traders. Cases were selected based on the World Health Organization (WHO) categorisation of malaria. For UM, the participants had a present or previous fever and a positive malaria test, and for SM, the participants had a previous or present fever, a positive test and a sign of organ dysfunction.
2.2. Sample Collection and Sample Analysis
5 mL of blood was aseptically collected and aliquoted into Ethylenediaminetetraacetic acid (EDTA) (2 mL) and serum separator tubes (3 mL). The EDTA sample was used for blood films (thin and thick) for the detection of malaria parasites according to the protocol described by Haggaz et al., (2014) and for full blood count (FBC) using a five (5) parts automated haematology analyser, Sysmex XN - 350 (Sysmex Corporation, Kobe, Japan 2019). The serum separator tube was allowed to clot and centrifuged at 3000rpm for 5 minutes and the serum separated into a plain tube, 1mLwas used for biochemical analysis (liver and renal function tests) using the LE - Scientific Fully Automated Chemistry Analyzer LE Max - 2000 (LE Scientific Medfuture, Hamburg, Germany, 2021). The rest stored at -20°C for the measurement of Angiopoietins -1 and -2 (ANG-1 & -2) levels by employing a double sandwich enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturer’s instructional manual (Melson Shanghai Chemical Ltd, 2020, ANG-1 KIT10062 ANG 2 -KIT10691) which works on the principle that any antigen present binds to the capture antibody once the sample is put to wells coated with a capture antibody. Before an enzyme-linked secondary antibody is administered and binds to the detecting antibody, an antigen-binding detecting antibody is first added. Following the addition of a substrate, this is changed by an enzyme to a form that can be detected.
2.3. Statistical Analysis
Statistical analyses were carried out using GraphPad Prism 9 software (GraphPad Software, San Diego, CA, USA). Statistically significant differences were set at a p-value <0.05. Mann-Whitney U test was performed to compare two groups, while the Kruskal-Wallis analysis was done to compare three or more groups, followed by Dunn’s Multiple Comparison tests. Correlations between two continuous variables of interest were tested using the nonparametric Spearman’s rank correlation (rho). Multiple logistic regression was performed to identify the best predictors of severe malaria. Descriptive analysis was done using tables of means, medians, quartile ranges, and variances.
2.4. Ethics and Consent
The study was approved by the Committee for Human Research, Publication and Ethics (CHRPE) of Kwame Nkrumah University of Science and Technology (KNUST). Reference number CHRPE/AP/129/21.
Table 1. Comparison of parasitaemia levels of uncomplicated and severe malaria within the various demographic characteristics.
Demographic characteristics
Uncomplicated malaria
Severe Malaria
n
Parasitaemia (/µL) Median (IQR)
P value
n
Parasitaemia (/µL) Median (IQR)
P value
Age range
<5
6
7346 (1994 - 26693)
16
29589 (17150 - 102905)
5-17
14
2808 (1397 - 7568)
14
29793 (14542 - 88230)
≥18
58
2670 (1109 - 6716)
0.649
16
5461 (1871 - 32617)
0.075
Sex
Female
42
2670 (680 - 6716)
22
26823 (2595 - 179603)
Male
36
3623 (1208 - 8470)
0.190
24
23542 (5856 - 57785)
0.744
Marital status
Single
26
2670 (1208 - 8470)
10
26823 (6542 - 50000)
Marriage
30
1275 (787 - 6112)
0.546
4
3079 (1777 - 4380)
0.120
Educationb
No education
Basic
36
2413 (840 - 4400)
14
29793 (9439 - 88705)
Secondary
18
4208 (2670 - 8676)
14
6542 (2282 - 40296)
0.037
Tertiary
8
1641 (947 - 4531)
0.071
NA
Occupationa
Student
18
2670 (1208 - 8470)
8
28271 (5250 - 53455)
Informal sector
32
3623 (1103 - 6586)
8
3141 (1871 - 9991)
0.253
Formal sector
6
2041 (1441 - 9510)
0.937
NA
-
a only participants ≥ 18 years were included; bonly participants ≥6 years were included; n = sample size; IQR = 1st-3rd quartile
3.2. Evaluation of Haematological and Biochemical Parameters as Biomarkers in Malaria Patients and Healthy Controls
Table 2 shows the comparison of clinical parameters as biomarkers in malaria patients (UM and SM) and HC. The parasite counts of the SM (24615, IQR: 3943 - 60541) population were significantly higher than UM (2808, IQR: 1090 - 8189). The haemoglobin and platelet count of SM patients were significantly lower than the UM group (p<0.05). However, the white blood cells (WBC) of SM patients (7.4, IQR: 5.4 - 10.6) were significantly higher than the UM population (5.7, IQR: 5.0 - 6.5) (p < 0.001). Serum levels of bilirubin (total and direct), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total protein in the SM were significantly higher than the uncomplicated malaria group (p < 0.001) (Table 2).
The median Ang-1 levels in SM were lower (3.8 ng/L, IQR: 2.2 - 12.7) in comparison to UM (6.3 ng/L, IQR: 3.3 - 8.0) and HC (9.6 ng/L, IQR: 3.5 - 15.3). Ang-2 levels were higher in SM (19.1ng/L, IQR: 9.0 - 25.8) compared to UM (15.7ng/L, IQR: 2.6 - 27.4), but this was not statistically significant (p=0.152).
Table 2. Comparison of clinical parameters and biomarkers in malaria patients and healthy controls.
Variable
Healthy controls (HC), n= 42
Uncomplicated malaria (UM), n=78
Severe malaria (SM), n = 46
P value for UM vs. SM
Haemoglobin
11.8 (11.3 - 12.4)
11.8 (10.8 - 13.1)
10.9 (9.2 - 12.5)
0.003
WBC
6.22 (5.0 - 8.1)
5.7 (5.0 - 6.5)
7.4 (5.4 - 10.6)
<0.001
Platelet count
270 (229 - 342)
149 (117 - 196)
108 (46 - 130)
<0.001
NEUT
41.6 (37.8 - 60.7)
69.8 (55.2 - 78.1)
71.5 (61.9 - 82.7)
0.124
LYMP
46.5 (30.3 - 53.3)
23.5 (14.9 - 33.5)
19.0 (12.1 - 29.9)
0.249
MXD
8.8 (7.2 - 10.2)
7.7 (6.1 -12.1)
7.9 (4.7 - 8.9)
0.012
Total Bilirubin
5.2 (3.8 - 6.2)
8.1 (5.4 - 10.7)
11.2 (7.4 - 24.3)
<0.001
Direct Bilirubin
2.1 (1.2 - 3.2)
3.4 (1.9 - 4.3)
6.6 (4.1 - 16.1)
<0.001
ALT
7 (6 - 8)
9 (5.3 - 11.8)
12 (10 - 18.7)
<0.001
AST
21 (13 - 26)
17 (12 - 23.3)
26 (16.3 - 50)
<0.001
GGT
18 (11 - 22)
20 (13.3 - 28.8)
40 (18.3 - 49.5)
<0.001
ALP
80 (66 - 97)
66 (49.3 - 107.5)
92 (67.8 - 126.8)
0.054
Total protein
69.2 (64.9 - 70.7)
64.1 (60 - 69.4)
68.3 (66.2 - 72.7)
0.002
Albumin
38.6 (37.1 - 41.6)
37.6 (35.9 - 39.7)
35.9 (31.7 -37.9)
0.002
Parasite count
NA
2808 (1090 - 8189)
24615 (3943 - 60541)
<0.001
Ang-1
9.6 (3.5 - 15.3)
6.3 (3.3 - 8.0)
3.8 (2.2 - 12.7)
0.129
Ang-2
18.7 (12.4 - 22.1)
15.7 (2.6 - 27.4)
19.1 (9.0 - 25.8)
0.429
Ang-2/Ang-1
1.9 (1.2 - 3.5)
2.0 (0.6 - 3.2)
3.1 (1.4 - 5.3)
0.152
WBC = White blood cell (×109/L); Neut. = Neutrophil (%); Lymph = Lymphocyte (%); Mxd. = Mixed Cell Count (%): ALT = alanine transaminase: AST = aspartate transaminase; GGT = gamma-glutamyl transferase; ALP = alkaline phosphatase; Ang-1 = Angiopoietin 1; Ang-2 = Angiopoietin 2, NA = Not Applicable
The serum creatinine of SM patients (95, IQR: 84.3 - 127.0) was significantly higher than UM (72.4, IQR: 59.8 - 90) and HC group (58, IQR: 43 - 74) (p <0.0001) (Figure 1). Similarly, the serum urea levels of SM patients (7.6, IQR: 5.3 - 9.3) were significantly higher than UM (5.6, IQR: 4.8 - 7.2) and the HC group (5.4, IQR: 4 - 6.5). However, the urea levels of UM and HC were comparable (p =0.001) (Figure 1).
Figure 1. Comparison of serum creatinine and urea levels in malaria patients (UM and SM) and healthy controls (HC).
3.3. Comparison of Estimated Glomerular Filtration Rate Between Healthy Controls Uncomplicated and Severe Malaria
The eGFR of SM patients (99, IQR: 64 - 138) was significantly lower than UM (129, IQR: 95 - 153) and HC group (136, IQR: 115 - 176) (p<0.05). However, eGFR values in the control group and those with uncomplicated malaria were comparable (p = 0.18) (Figure 2).
Figure 3. Assessment of angiopoietin levels in discriminating between severe malaria (SM) and uncomplicated malaria (UM).
4. Discussion
Malaria is a serious public health issue in Ghana and Sub-Saharan Africa, where it causes more infections and fatalities than in many other regions. This work demonstrated that children less than 5 years old recorded the highest number of parasites in comparison to other age groups. This age group has not fully developed immunity to malaria, hence the reason for the high parasite numbers recorded as compared to the older age groups, who have suffered repeated bites of mosquitoes to build immunity. Again, those with basic education significantly recorded higher parasitaemia than their secondary or higher education counterparts. This result, therefore, supports a study conducted by
[11]
Awosolu, O. B. et al. (2021) ‘Prevalence, Parasite Density and Determinants of Falciparum Malaria Among Febrile Children in Some Peri-Urban Communities in Southwestern Nigeria: A Cross-Sectional Study’, Infection and drug resistance, pp. 3219-3232.
[11]
. This higher level of parasitaemia seen in people with low educational levels may be because people who have a higher education have acquired knowledge of malaria transmission, prevention, and control.
This study's results showed a statistically significant difference in haemoglobin levels between patients with severe malaria and those with uncomplicated malaria. The sequestration of red blood cells that occurs during and even after treatment for malaria may be the cause of the lower haemoglobin levels in the severe malaria group. The lower levels of haemoglobin among the SM group are in agreement with research published earlier
[12]
Ayyadevara, R. (2022) ‘Effect of malaria on biochemical and haematological parameters: a hospital-based case-control study’, MRIMS Journal of Health Sciences, 10(3), pp. 41-46.
[13]
Squire, D. S. et al. (2016) ‘Effect of Plasmodium falciparum malaria parasites on haematological parameters in Ghanaian children’, Journal of parasitic diseases, 40, pp. 303-311.
[12, 13]
. Additionally, a significantly low platelet count was observed and this outcome is in line with past research findings, which found that severe cases of malaria were associated with lower platelet counts
[14]
Bhattacharya, D. (2016) ‘Indian Monsoon Climate and Malaria: Medical Meteorology’, Journal of Malaria Control & Elimination, 5(2), pp. 2-6.
[15]
Devineni, S. B. et al. (2015) ‘Study of platelet count in malaria patients and the correlation between the presence and severity of platelet count with type of malaria’, Journal of Evolution of Medical and Dental Sciences, Malaria surveillance-United States, pp. 1-17.
[16]
Kumar, N. (2016) ‘Correlation of type of species and parasite density in malaria with platelet count, mean platelet volume and platelet distribution width’, Journal of Evolution of Medical and Dental Sciences-Jemds, 5(89), pp. 6622-6625.
[14-16]
. Humoral immune response in conjunction with a hyper-reactive spleen may be the cause of the reduced platelet count seen among severe malaria patients who were enrolled in this study.
Serum levels of total and direct bilirubin, AST, ALT, ALP, and GGT were all significantly higher in the group with SM than in the group with UM (p< 0.05). The above findings support a study that found that patients with falciparum malaria had significantly higher serum levels of ALP, AST, ALT, total bilirubin, and direct bilirubin (p < 0.0001). The elevated levels of serum liver enzymes, transaminases (AST and ALT), and ALP represent the markers of hepatic injury. The indicators of liver injury are elevated serum levels of hepatic enzymes, transaminases (AST and ALT), and alkaline phosphatase. It has been previously reported that the elevation in enzymes of the hepatocytes is due to leakage; likewise, the elevated levels of bilirubin (total and direct) are also because of haemolysed red blood cells by increased density of plasmodium parasites
[17]
Asare, I. D. (2019) ‘Evaluation of Renal and Hepatic Dysfunction among Children Less than Five Years with Malaria in Jasikan District, Oti Region-Ghana’. University of Ghana. 4(67), pp. 11734-11747.
[17]
.
Renal injuries are usually seen as one of the complications of SM, mostly in the older age group
[18]
Koopmans, L. C. et al., (2015) ‘Acute kidney injury in imported Plasmodium falciparum malaria’, Malaria journal, 14(1), pp. 1-7.
[18]
. Some studies have reported some percentages of acute kidney injury (AKI) in severe malaria patients
[18]
Koopmans, L. C. et al., (2015) ‘Acute kidney injury in imported Plasmodium falciparum malaria’, Malaria journal, 14(1), pp. 1-7.
[19]
Storm, J., & Craig, A. G. (2014). Pathogenesis of cerebral malaria—inflammation and cytoadherence. Frontiers in cellular and infection microbiology, 4, 100.
[18, 19]
. Markers such as urea and creatinine usually peak during severe malaria episodes. From this study, results indicate that serum creatinine and urea of SM patients were significantly higher than in UM and HC groups. The high creatinine and urea levels observed in this, and several other studies are the main features of acute kidney injuries (AKI) associated with SM. According to
[20]
Fang, Y., Li, C., Shao, R., Yu, H., & Zhang, Q. (2018). The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: a prospective observational study. Thrombosisresearch, 171, 149-154.
[20]
, SM causes damage to the glomerulus, interstitial areas, and tubules, which leads to AKI. This presentation is very consistent with studies conducted by
[21]
Vinhaes, C. L., et al. (2021). Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation. PLoS Neglected Tropical Diseases, 15(11), e0009886.
[21]
, who found that SM cases had higher serum creatinine and urea levels than groups who had UM and HC.
This study's results for the estimated eGFR indicated that the SM group had significantly lower eGFR as compared with their UM counterparts and HC. These findings therefore support studies conducted by
[22]
Rivera-Correa, et al. (2019). Autoantibody levels are associated with acute kidney injury, anaemia and post-discharge morbidity and mortality in Ugandan children with severe malaria. Scientific Reports, 9(1), 14940.
[23]
Bhardwaj, N., et al. (2020). Clinicopathological study of potential biomarkers of Plasmodium falciparum malaria severity and complications. Infection, Genetics and Evolution, 77, 104046.
[22, 23]
who reported similar lower eGFR in patients having SM infection. This alteration in the function of the kidney in terms of fluid output, resulting in lower eGFR in SM may be a result of rosette formation or sequestration in blood vessels, which reduces blood supply to the kidneys. This then results in high levels of creatinine accumulation, leading to acute kidney injury
[23]
Bhardwaj, N., et al. (2020). Clinicopathological study of potential biomarkers of Plasmodium falciparum malaria severity and complications. Infection, Genetics and Evolution, 77, 104046.
[23]
.
Although the results of this study did not indicate whether Ang-1 and Ang-2 could be used to predict which of the subjects with uncomplicated malaria is slowly progressing to severe malaria, the evidence provided by the results nonetheless showed that decreased Ang-1 and increased Ang-2 levels are indicators of severe malaria disease
[24]
Storm, J., & Craig, A. G. (2014). Pathogenesis of cerebral malaria—inflammation and cytoadherence. Frontiers in cellular and infection microbiology, 4, 100.
[24]
. As a result, in terms of endothelium activation and the severity of the sickness, the ratio between Ang-2 and Ang-1 may be the most advantageous
[25]
Fang, Y., et al. (2018). The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: a prospective observational study. Thrombosis research, 171, 149-154.
[25]
.
Limitations to this current study include a lack of molecular diagnosis of malaria, a small sample size, and a lack of past medical histories could potentially alter the interpretations of the results.
5. Conclusion
In summary, the results of this research demonstrate that haemoglobin, platelet, AST, ALT, ALP, GGT, creatinine and urea have the potential to serve as biomarkers of both UM and SM. Haematological and biochemical investigations are not expensive and simple to perform. These markers serve as desirable candidates for differentiating UM from SM in a Ghanaian population.
Abbreviations
UM
Uncomplicated Malaria
SM
Severe Malaria
WHO
World Health Organization
EDTA
Ethylenediaminetetraacetic Acid
ELISA
Enzyme-linked Immunosorbent Assay
mL
Milliliters
FBC
Full Blood Count
ANG
Angiopoietins
HC
Healthy Controls
IQR
Interquartile Range
ALT
Alanine Transaminase
AST
Aspartate Transaminase
GGT
Gamma-Glutamyl Transferase
ALP
Alkaline Phosphatase
eGFR
Estimated Glomerular Filtration Rate
AKI
Acute Kidney Injury
Acknowledgments
The authors appreciate the contribution of the staff of Bremang SDA Hospital and the Wenchi Methodist Hospital Laboratory staff. We are thankful to Dr. Charles Nkansah of the University for Development Studies, Tamale. We again appreciate all the participants of this study.
Funding
The authors did not receive any funding for this work.
Data Availability Statement
Available on demand.
Author Contributions
Enoch Boadi: Conceptualisation, Investigation, Methodology, Writing- original draft
Max Efui Annani-Akollor: Supervision
Christopher Nkrumah: Conceptualisation, Methodology
Ellis Kobina Paintsil: Data curation, Formal Analysis
Anthony Eric Eshun: Investigation, Methodology
Lydia Omari: Project Administration
Yaw Frimpong: Resources
Egote Alexander Kofi: Writing – original draft, Writing – review & editing
Conflicts of Interest
No conflict of interest from any author.
References
[1]
Cullen, K. A. et al. (2011) ‘Division of parasitic diseases and malaria’, Centre for Global Health, Centres for Disease Control and Prevention (CDC).
[2]
Anvikar, A. R. et al. (2020) ‘Clinical and epidemiological characterisation of severe Plasmodium vivax malaria in Gujarat.
[3]
Diema Konlan, K. et al. (2019) ‘Utilisation of insecticide-treated bed nets (ITNs) among caregivers of children under five years in the Ho municipality’, Interdisciplinary.
[4]
Higgins, S. et al. (2016) ‘Dysregulation of angiopoietin 1 plays a mechanistic role in the pathogenesis of cerebral malaria. Science translational medicine,8(358),358ra 128. pp. 1-25. Available at:
Lovegrove, F. E., et al. (2009) ‘Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children’, PLoS ONE, 4(3), pp. 1-8. Available at:
Snow, R. W. et al., (2005) ‘The global distribution of clinical episodes of Plasmodium falciparum malaria’, Nature, 434(7030), pp. 214-217.
[7]
Li, G. et al.,(2020) ‘Distribution of malaria patients seeking care in different types of health facilities during the implementation of National Malaria Elimination Programme’, Malaria journal, 19(1), pp. 1-10.
[8]
Dhangadamajhi, G. et al. (2019) ‘Effect of Plasmodium falciparum infection on blood parameters and their association with clinical severity in adults of Odisha, India’, Acta tropica, 190, pp. 1-8. Perspectives on infectious diseases, 2019.
[9]
Muwonge, H. et al.(2013) ‘How reliable are haematological parameters in predicting uncomplicated Plasmodium falciparum malaria in an endemic region?’, International Scholarly Research Notices, 2013(1), p. 673798.
[10]
Zuberi, U. et al. (2024) ‘Altered haematological parameters in children with malaria infection, a systematic review and meta-analysis’, Diagnostic Microbiology and Infectious Disease, 108(4), p. 116190.
[11]
Awosolu, O. B. et al. (2021) ‘Prevalence, Parasite Density and Determinants of Falciparum Malaria Among Febrile Children in Some Peri-Urban Communities in Southwestern Nigeria: A Cross-Sectional Study’, Infection and drug resistance, pp. 3219-3232.
[12]
Ayyadevara, R. (2022) ‘Effect of malaria on biochemical and haematological parameters: a hospital-based case-control study’, MRIMS Journal of Health Sciences, 10(3), pp. 41-46.
[13]
Squire, D. S. et al. (2016) ‘Effect of Plasmodium falciparum malaria parasites on haematological parameters in Ghanaian children’, Journal of parasitic diseases, 40, pp. 303-311.
[14]
Bhattacharya, D. (2016) ‘Indian Monsoon Climate and Malaria: Medical Meteorology’, Journal of Malaria Control & Elimination, 5(2), pp. 2-6.
[15]
Devineni, S. B. et al. (2015) ‘Study of platelet count in malaria patients and the correlation between the presence and severity of platelet count with type of malaria’, Journal of Evolution of Medical and Dental Sciences, Malaria surveillance-United States, pp. 1-17.
[16]
Kumar, N. (2016) ‘Correlation of type of species and parasite density in malaria with platelet count, mean platelet volume and platelet distribution width’, Journal of Evolution of Medical and Dental Sciences-Jemds, 5(89), pp. 6622-6625.
[17]
Asare, I. D. (2019) ‘Evaluation of Renal and Hepatic Dysfunction among Children Less than Five Years with Malaria in Jasikan District, Oti Region-Ghana’. University of Ghana. 4(67), pp. 11734-11747.
[18]
Koopmans, L. C. et al., (2015) ‘Acute kidney injury in imported Plasmodium falciparum malaria’, Malaria journal, 14(1), pp. 1-7.
[19]
Storm, J., & Craig, A. G. (2014). Pathogenesis of cerebral malaria—inflammation and cytoadherence. Frontiers in cellular and infection microbiology, 4, 100.
[20]
Fang, Y., Li, C., Shao, R., Yu, H., & Zhang, Q. (2018). The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: a prospective observational study. Thrombosisresearch, 171, 149-154.
[21]
Vinhaes, C. L., et al. (2021). Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation. PLoS Neglected Tropical Diseases, 15(11), e0009886.
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Boadi, E., Annani-Akollor, M. E., Nkrumah, C., Paintsil, E. K., Eshun, A. E., et al. (2026). Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa. American Journal of Laboratory Medicine, 11(1), 1-8. https://doi.org/10.11648/j.ajlm.20261101.11
Boadi, E.; Annani-Akollor, M. E.; Nkrumah, C.; Paintsil, E. K.; Eshun, A. E., et al. Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa. Am. J. Lab. Med.2026, 11(1), 1-8. doi: 10.11648/j.ajlm.20261101.11
Boadi E, Annani-Akollor ME, Nkrumah C, Paintsil EK, Eshun AE, et al. Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa. Am J Lab Med. 2026;11(1):1-8. doi: 10.11648/j.ajlm.20261101.11
@article{10.11648/j.ajlm.20261101.11,
author = {Enoch Boadi and Max Efui Annani-Akollor and Christopher Nkrumah and Ellis Kobina Paintsil and Anthony Eric Eshun and Lydia Omari and Yaw Frimpong and Egote Alexander Kofi},
title = {Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa},
journal = {American Journal of Laboratory Medicine},
volume = {11},
number = {1},
pages = {1-8},
doi = {10.11648/j.ajlm.20261101.11},
url = {https://doi.org/10.11648/j.ajlm.20261101.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajlm.20261101.11},
abstract = {Malaria is classified as either uncomplicated (UM) or severe (SM), but the mechanism underlying the progression from uncomplicated to severe is still unclear. This study aimed to assess haematologic and biochemical parameters as potential prognostic biomarkers for differentiating SM from UM in a Ghanaian population. A descriptive cross-sectional study was conducted to sample 166 participants, comprising 42 healthy controls, 78 uncomplicated malaria cases, and 46 severe malaria cases. Blood samples were analysed for full blood count, liver function test, renal function test, and serum angiopoietins. Statistical analyses were carried out using GraphPad Prism 9 software. Median and interquartile ranges, Mann-Whitney U test, and Kruskal-Wallis analysis were done to compare groups. The haemoglobin and platelet counts of SM patients were significantly lower than those of the UM group (p < 0.05). However, the White Blood Cell (WBC) counts of severe malaria patients (7.4, IQR: 5.4 - 10.6) were significantly higher than the uncomplicated malaria population (5.7, IQR: 5.0 - 6.5) (p < 0.001). Serum levels of bilirubin (total and direct), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total proteins in severe malaria were significantly higher than uncomplicated malaria group (p < 0.001). These findings indicate that haemoglobin, platelet, creatinine, urea, AST, ALT, GGT and bilirubin levels may serve as biomarkers for distinguishing severe from uncomplicated malaria.},
year = {2026}
}
TY - JOUR
T1 - Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa
AU - Enoch Boadi
AU - Max Efui Annani-Akollor
AU - Christopher Nkrumah
AU - Ellis Kobina Paintsil
AU - Anthony Eric Eshun
AU - Lydia Omari
AU - Yaw Frimpong
AU - Egote Alexander Kofi
Y1 - 2026/01/16
PY - 2026
N1 - https://doi.org/10.11648/j.ajlm.20261101.11
DO - 10.11648/j.ajlm.20261101.11
T2 - American Journal of Laboratory Medicine
JF - American Journal of Laboratory Medicine
JO - American Journal of Laboratory Medicine
SP - 1
EP - 8
PB - Science Publishing Group
SN - 2575-386X
UR - https://doi.org/10.11648/j.ajlm.20261101.11
AB - Malaria is classified as either uncomplicated (UM) or severe (SM), but the mechanism underlying the progression from uncomplicated to severe is still unclear. This study aimed to assess haematologic and biochemical parameters as potential prognostic biomarkers for differentiating SM from UM in a Ghanaian population. A descriptive cross-sectional study was conducted to sample 166 participants, comprising 42 healthy controls, 78 uncomplicated malaria cases, and 46 severe malaria cases. Blood samples were analysed for full blood count, liver function test, renal function test, and serum angiopoietins. Statistical analyses were carried out using GraphPad Prism 9 software. Median and interquartile ranges, Mann-Whitney U test, and Kruskal-Wallis analysis were done to compare groups. The haemoglobin and platelet counts of SM patients were significantly lower than those of the UM group (p < 0.05). However, the White Blood Cell (WBC) counts of severe malaria patients (7.4, IQR: 5.4 - 10.6) were significantly higher than the uncomplicated malaria population (5.7, IQR: 5.0 - 6.5) (p < 0.001). Serum levels of bilirubin (total and direct), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total proteins in severe malaria were significantly higher than uncomplicated malaria group (p < 0.001). These findings indicate that haemoglobin, platelet, creatinine, urea, AST, ALT, GGT and bilirubin levels may serve as biomarkers for distinguishing severe from uncomplicated malaria.
VL - 11
IS - 1
ER -
Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;Laboratory Department, Wenchi Methodist Hospital, Wenchi, Ghana
Laboratory Department, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana;Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Boadi, E., Annani-Akollor, M. E., Nkrumah, C., Paintsil, E. K., Eshun, A. E., et al. (2026). Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa. American Journal of Laboratory Medicine, 11(1), 1-8. https://doi.org/10.11648/j.ajlm.20261101.11
Boadi, E.; Annani-Akollor, M. E.; Nkrumah, C.; Paintsil, E. K.; Eshun, A. E., et al. Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa. Am. J. Lab. Med.2026, 11(1), 1-8. doi: 10.11648/j.ajlm.20261101.11
Boadi E, Annani-Akollor ME, Nkrumah C, Paintsil EK, Eshun AE, et al. Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa. Am J Lab Med. 2026;11(1):1-8. doi: 10.11648/j.ajlm.20261101.11
@article{10.11648/j.ajlm.20261101.11,
author = {Enoch Boadi and Max Efui Annani-Akollor and Christopher Nkrumah and Ellis Kobina Paintsil and Anthony Eric Eshun and Lydia Omari and Yaw Frimpong and Egote Alexander Kofi},
title = {Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa},
journal = {American Journal of Laboratory Medicine},
volume = {11},
number = {1},
pages = {1-8},
doi = {10.11648/j.ajlm.20261101.11},
url = {https://doi.org/10.11648/j.ajlm.20261101.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajlm.20261101.11},
abstract = {Malaria is classified as either uncomplicated (UM) or severe (SM), but the mechanism underlying the progression from uncomplicated to severe is still unclear. This study aimed to assess haematologic and biochemical parameters as potential prognostic biomarkers for differentiating SM from UM in a Ghanaian population. A descriptive cross-sectional study was conducted to sample 166 participants, comprising 42 healthy controls, 78 uncomplicated malaria cases, and 46 severe malaria cases. Blood samples were analysed for full blood count, liver function test, renal function test, and serum angiopoietins. Statistical analyses were carried out using GraphPad Prism 9 software. Median and interquartile ranges, Mann-Whitney U test, and Kruskal-Wallis analysis were done to compare groups. The haemoglobin and platelet counts of SM patients were significantly lower than those of the UM group (p < 0.05). However, the White Blood Cell (WBC) counts of severe malaria patients (7.4, IQR: 5.4 - 10.6) were significantly higher than the uncomplicated malaria population (5.7, IQR: 5.0 - 6.5) (p < 0.001). Serum levels of bilirubin (total and direct), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total proteins in severe malaria were significantly higher than uncomplicated malaria group (p < 0.001). These findings indicate that haemoglobin, platelet, creatinine, urea, AST, ALT, GGT and bilirubin levels may serve as biomarkers for distinguishing severe from uncomplicated malaria.},
year = {2026}
}
TY - JOUR
T1 - Haematologic and Biochemical Parameters to Differentiate Severe Malaria from Uncomplicated Malaria in a Ghanaian Population in Sub-Saharan Africa
AU - Enoch Boadi
AU - Max Efui Annani-Akollor
AU - Christopher Nkrumah
AU - Ellis Kobina Paintsil
AU - Anthony Eric Eshun
AU - Lydia Omari
AU - Yaw Frimpong
AU - Egote Alexander Kofi
Y1 - 2026/01/16
PY - 2026
N1 - https://doi.org/10.11648/j.ajlm.20261101.11
DO - 10.11648/j.ajlm.20261101.11
T2 - American Journal of Laboratory Medicine
JF - American Journal of Laboratory Medicine
JO - American Journal of Laboratory Medicine
SP - 1
EP - 8
PB - Science Publishing Group
SN - 2575-386X
UR - https://doi.org/10.11648/j.ajlm.20261101.11
AB - Malaria is classified as either uncomplicated (UM) or severe (SM), but the mechanism underlying the progression from uncomplicated to severe is still unclear. This study aimed to assess haematologic and biochemical parameters as potential prognostic biomarkers for differentiating SM from UM in a Ghanaian population. A descriptive cross-sectional study was conducted to sample 166 participants, comprising 42 healthy controls, 78 uncomplicated malaria cases, and 46 severe malaria cases. Blood samples were analysed for full blood count, liver function test, renal function test, and serum angiopoietins. Statistical analyses were carried out using GraphPad Prism 9 software. Median and interquartile ranges, Mann-Whitney U test, and Kruskal-Wallis analysis were done to compare groups. The haemoglobin and platelet counts of SM patients were significantly lower than those of the UM group (p < 0.05). However, the White Blood Cell (WBC) counts of severe malaria patients (7.4, IQR: 5.4 - 10.6) were significantly higher than the uncomplicated malaria population (5.7, IQR: 5.0 - 6.5) (p < 0.001). Serum levels of bilirubin (total and direct), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total proteins in severe malaria were significantly higher than uncomplicated malaria group (p < 0.001). These findings indicate that haemoglobin, platelet, creatinine, urea, AST, ALT, GGT and bilirubin levels may serve as biomarkers for distinguishing severe from uncomplicated malaria.
VL - 11
IS - 1
ER -