E-ISSN: 2814 – 1822; P-ISSN: 2616 – 0668
ORIGINAL RESEARCH ARTICLE
Hauwa’u Yunusa*, Mohammed Nasiru Shuaibu and Ismail Alhaji Umar
Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
*Corresponding author: yunusahauwa5@gmail.com
Significant alterations in biochemical and haematological markers primarily characterise the development of malaria. The objective of this study was to analyse the serum lipid and protein profiles, as well as some haematological markers, in children under the age of five who are infected with the malaria parasite. The study was conducted at the Department of Paediatric, Ahmadu Bello University Teaching Hospital in Zaria, Kaduna state. A cross-sectional study was performed on a sample of 316 children with malaria and 100 children who were seemingly healthy and under the age of five. Among the 316 patients, 50 (15.8%) tested positive for malaria, while 20 samples from persons who appeared to be in good health were examined. Significant reductions (p<0.05) in cholesterol (mean±SD: 0.450±0.026 mmol/L vs. 0.907±0.069 mmol/L), triglycerides (mean±SD: 0.326±0.058 mmol/L vs. 0.461±0.123 mmol/L), and albumin (mean±SD: 5.23±2.82 g/L vs. 2.82±2.18 g/L) were observed in malaria-positive children compared to healthy controls, indicating potential biomarkers for malaria severity.
Keywords: Biochemicals, child-health, haematologicals, malaria, mortality and parasites
Malaria is caused by a parasitic organism that undergoes part of its life cycle in people and the remaining portion in mosquitoes. Malaria continues to be a prominent cause of death worldwide, endangering the lives of almost a third of the global population (WHO, 2024). A significant proportion of children residing in malaria-endemic regions of Africa experience at least one episode of severe malaria throughout their early years of life (Goncalves et al., 2014).
Globally, the burden of malaria in the WHO African Region remains disproportionately high. Approximately 78% of all malaria-related fatalities in the region occurred in children under the age of 5 (WHO, 2024). Cerebral malaria and severe anaemia are the most prevalent and consequential consequences of Plasmodium falciparum malaria in children (Luzolo and Ngoyi, 2019).
The liver, which is the main location where Plasmodium infection occurs, produces cholesterol. This has led to investigations into the possible relationship between the liver's cholesterol synthesis and the infection of the liver by Plasmodium (Akanbi et al., 2012). The liver maintains the balance of lipid and lipoprotein metabolism to ensure homeostasis. Hepatocellular injury, a frequent occurrence in severe and acute P. falciparum infections, hinders these processes and alters the composition of plasma lipids and lipoproteins (Sibmooh et al., 2004).
The alterations in the lipid profile found in the blood serum can be ascribed to the degree of haemolysis caused by malaria, which is directly related to the intensity of the infection (Abdulazeez et al., 2017). Elevated cholesterol levels, resulting from malaria and reduced levels of endogenous antioxidants, increase the likelihood of reactive oxygen species (ROS) production. Reactive oxygen species (ROS) can interact with various biological molecules, including DNA, lipids, proteins, and carbohydrates, resulting in damage to cellular components (Checa and Aran, 2020).
Despite advancements in malaria control, it remains a leading cause of morbidity and mortality in sub-Saharan Africa, particularly among children under five (WHO, 2024). Recent statistics indicate over 200 million cases and approximately 400,000 deaths annually (Adegunloye, 2018), implying the need for further research into biochemical and haematological changes associated with malaria infection in under five children.
This research was carried out at the Department of Paediatrics, Ahmadu Bello Teaching Hospital (ABUTH), Shika, Zaria, Kaduna State, Nigeria.
This cross-sectional study enrolled 316 malaria-positive and 100 healthy children under five. The sample size was calculated based on an expected prevalence of biochemical changes of 20%, with a confidence level of 95% and power of 80%. Participants were randomly selected from the Paediatrics Department.
This study obtained ethical approval (NHREC/10/12/2015) from the Ethics Review Committee of Ahmadu Bello University Teaching Hospital. Participation in the study was entirely optional and dependent upon parents or caregivers providing written informed consent.
The participants' socio-demographic data were obtained after obtaining written informed consent from their parents or carers, with the assurance of confidentiality and anonymity. Every participant provided 3 mL of whole blood. Giemsa staining was used to detect, identify, and estimate parasites in both thick and thin blood films, following the methods described by Chessbrough (2009). Capillary tubes were employed for the detection of PCV and Hb. The serum was stored in a refrigerator until it was required for additional analysis.
The levels of cholesterol, low-density lipoproteins, triglycerides, albumin, globulin, and proteins were measured using the methods and principles outlined by Friedewald et al. (1972), Tietz (1986), Doumas et al. (1971), and Berne and Levy (1975)f accordingly.
In addition, the packed cell volume (PCV) and haemoglobin (Hb) were measured using the Jain (1986) technique.
Data were analyzed using ANOVA and post hoc Tukeys tests for multiple comparisons.
Among the 316 patients showing symptoms of malaria and the 100 apparently healthy children serving as controls, 50 individuals (15.8%) were diagnosed with malaria. Additionally, 20 of the control children were selected for additional study of their biochemical and haematological profiles.
Figure 1. The prevalence of P. falciparum malaria parasite infection based on gender distribution
Figure 1 illustrates a higher incidence of malaria in males (58%) compared to females (42%), suggesting potential sex-based susceptibility differences. Table 1 shows significant reductions in cholesterol (p=0.000), LDL (p=0.000), and albumin (p=0.003) levels in malaria-positive children, highlighting the potential use of these markers in assessing malaria severity. However, there is no statistically significant difference between malaria patients and the negative control group in terms of packed cell volume (p-1.750) and haemoglobin (p-0.139), as shown in Table 2.
Figure 2. The prevalence of P. falciparum malaria parasite infection according to age distribution
Table 1. Serum estimation of biochemical parameters in malaria positive and control in under five children attending Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Shika, Zaria, Kaduna state
Biochemical parameters | Malaria Positive (SD) | Malaria Negative Control (SD) | p-value |
---|---|---|---|
Cholesterol (mmol/L) | .45026 | .90698 | 0.000 |
High density lipoprotein (mmol/L) | .48969 | .48653 | 0.005 |
Low density lipoprotein (mmol/L) | .23702 | .64911 | 0.000 |
Triglyceride (mmol/L) | .32579 | .46123 | 0.000 |
Albumin (g/L) | 5.23259 | 2.81864 | 0.003 |
Globulin (g/L) | 6.71486 | 3.25212 | 0.042 |
Protein (g/L) | 6.61726 | 3.54520 | 0.829 |
Table 2. Estimation of haematological parameters in malaria positive and control in under five children attending Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Shika, Zaria, Kaduna state
Haematological parameters | Malaria Positive (SD) | Malaria Negative Control (SD) | p-value |
---|---|---|---|
Packed cell volume (%) | 7.00790 | 5.49521 | 1.750 |
Haemoglobin (g/dL) | 2.33289 | 1.83148 | 0.139 |
This study indicates that males are more vulnerable to malaria infection than females. This finding is consistent with the findings of Akanbi et al. (2010). Furthermore, research findings suggest that genetic and hormonal variables have a role in females having a stronger immune response to parasite infections (Zuk et al., 1996).
Moreover, the findings indicate a greater quantity of children between the ages of 3 and 5 in comparison to those between the ages of 0 and 2. The reason for this is that the majority of children admitted to the Department of Paediatric, Ahmadu Bello University Teaching Hospital, Zaria fall between the age range of 5 to 10, with a larger proportion falling between 2 and 5 years old. The World Health Organisation (WHO, 2007) agrees with the findings of this study about the association between malaria infection and age.
The blood lipid profile results obtained in this study were lower than those of the control group, including high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol. However, all values were within the normal range. In line with this research, Chikezie and Okpara (1996) found that individuals with moderate malaria infection had decreased serum levels of low-density lipoprotein and high-density lipoprotein compared to the control group.
Furthermore, the findings of this research correlate with the results of Baptisa et al. (1996), which indicated that children residing in regions susceptible to malaria exhibited notably reduced levels of cholesterol, triglycerides, HDLc, and LDLc in their plasma. Ogbodo et al. (2008) saw noteworthy reductions in both total cholesterol and HDL levels when comparing them to the control group's results. They stated that the decrease in overall cholesterol levels could be attributed to a substantial decrease in HDL, likely caused by oxidative modification.
Mohanty et al. (1992) examined alterations in plasma lipids induced by Plasmodium falciparum malaria in a sample of 83 individuals who were in good health, 60 individuals with severe malaria, and 23 individuals with mild malaria. The researchers quantified the concentrations of high-density lipoproteins, low-density lipoproteins, total cholesterol, and triglycerides in the plasma. The patients exhibited lower triglyceride levels compared to the controls, which agrees with the findings of this study. In their study, Al-Omar et al. (2010) observed a significant negative correlation between the number of parasites and the level of cholesterol in the blood serum of 200 malaria patients and 200 healthy blood donors of the same age. Increased parasitemia correlated with decreased serum cholesterol levels.
Parola et al. (2013) conducted a study that found that reduced HDL and potentially LDL levels are the main factors contributing to the low cholesterol levels observed in malaria. Undoubtedly, a parasitic element connects the reduction in cholesterol transport, esterification by lecithin cholesterol acyl transferase, and/or liver enzyme inhibition to the diminished levels of HDL. Hypocholesterolemia is primarily caused by the parasite's absorption of cholesterol and phospholipids from the host and the negative impact on enzymes responsible for creating HDL. These factors contribute to the development of hypocholesterolemia. In contrast, malaria can rapidly decrease HDL levels due to the accelerated removal of the substance from cells, surpassing its production rate (Mohanty et al., 1992; Nilsson-Ehle and Nilsson-Ehle, 1990).
In this study, the malaria patients exhibited significantly lower total protein, albumin, and globulin levels compared to the controls. This finding correlates with the assertions put forth by McKenzie et al. (2005) and Adebisi et al. (2002). Albumin has various physiological effects. For instance, it directly affects the vascular endothelium by binding to the endothelial glycocalyx, which helps maintain normal permeability (Curry et al., 1993).
Additionally, it has complex effects on erythrocytes (Reinheart et al., 1995). These characteristics suggest that albumin may have a role in the pathophysiology of malaria, particularly cerebral malaria. The albumin molecule's strong negative charge influences the adherence of parasitised red cells to the endothelium, the aggregation of red cells, and the loss of red cell deformability (Emmerson, 1989).
Haematological parameters, such as packed cell volume (PCV) and haemoglobin levels, play a crucial role in the treatment of individuals with malaria. The results obtained from this study show that the PCV value is slightly lower in malaria-infected subjects than in the control group. The decrease in PCV level, sometimes known as anaemia, in malaria-infected individuals, may be attributed to a certain level of haemolysis (Hoffbrand et al., 2005). Another possible cause could be normocytic or normochromic anaemia, namely the type associated with chronic illness, which has been observed in individuals infected with malaria (Hoffbrand et al., 2006).
Similarly, in Ibadan, in south-western Nigeria, Igbeneghu (2005) recorded a prevalence rate of 66.3% for anaemia among children who were infected with malaria. Furthermore, studies conducted in other African countries discovered a prevalence rate of 83.6% and 56.3%, respectively (Valerian et al., 2013). Also, the data obtained indicate a significant decrease in the haemoglobin level among the infected individuals compared to the control group, corresponding to the findings reported by Rosenthal et al. (2004).
Based on the findings of this study, the results establish the relationship between malaria, bbiochemical and some haematological parameters. This finding also demonstrates a significant difference in terms of age and gender among under five children within the study area.
Abdulazeez, A. M., Mukhtar, H. S., Binta, M. A., & Halliru, A. H. (2017). Prevalence, serum lipid profile and electrolyte levels of malaria-infected patients attending Sheikh Muhammad Jidda Specialist Hospital, Kano State, Nigeria. Bayero Journal of Medical Laboratory Science, 2(1), 2.
Adebisi, S. A., Soladoye, A. O., Adekoya, D., & Odunkanmi, O. A. (2002). Serum protein fractions of Nigerians with Plasmodium infections: Ilorin experience. African Journal of Clinical and Experimental Microbiology, 3(2), 82–84. [Crossref]
Adegunloye, A. P. (2018). In vitro and in vivo antimalarial, antioxidant and toxicological effects of methyl gallate and palmatine combination [Doctoral dissertation, University of Ilorin].
Akanbi, O. M., Badaki, J. A., Adeniran, O. Y., & Olotu, O. O. (2010). Effect of blood group and demographic characteristics on malaria infection, oxidative stress and haemoglobin levels in South Western Nigeria. African Journal of Microbiology Research, 4(9), 877–880.
Akanbi, O. M., Omonkhua, A. A., Cyril-Olutayo, C. M., & Fasimoye, R. Y. (2012). The antiplasmodial activity of Anogeissus leiocarpus and its effect on oxidative stress and lipid profile in mice infected with Plasmodium bergheii. Parasitology Research, 110(1), 219–226. [Crossref]
Al-Omar, I. A., Eligail, A. M., Al-Ashban, R. M., & Shah, A. H. (2010). Effect of falciparum malaria infection on blood cholesterol and platelets. Journal of Saudi Chemical Society, 14(1), 83–89. [Crossref]
Baptisa, J. L., Vervoort, T., Vander, S. P., & Wery, M. (1996). Changes in plasma lipid levels as a function of Plasmodium falciparum infection in Sao Tome. Parasite, 3(4), 335–340. [Crossref]
Berne, R. M., Levy, M., St. Louis, C. V., Mosby, & Finlayson, J. S. (1975). Physical and biochemical properties of human albumin. In J. T. Sgouris & A. Rene (Eds.), Proceedings of the workshop on albumin (pp. 31–56).
Bouyou-Akotet, M. K., Arnaud, D., Eric, K., Diane, E., Edgard, B. N., Timothy, P., Jean, K., & Marryvonne, K. (2009). Impact of Plasmodium falciparum infections on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon. Malaria Journal, 8, 166. [Crossref]
Checa, J., & Aran, J. M. (2020). Reactive oxygen species: Drivers of physiological and pathological processes. Journal of Inflammation Research, 13, 1057–1073. [Crossref]
Chessbrough, M. (2009). District laboratory practice in tropical countries (2nd ed., Vol. 1). Cambridge University Press.
Chikezie, P. C., & Okpara, R. T. (1996). Serum lipid profile and hepatic dysfunction in moderate Plasmodium falciparum infection. Global Journal of Medical Research: Diseases, 13(4), 14–20.
Curry, F. E., & He, P. (1993). Albumin modulation of capillary permeability: Role of endothelial cell [Ca2+]. American Journal of Physiology, 265(1), 74–82. [Crossref]
Das, B. S., Thurnham, D. J., & Das, D. B. (1997). Influence of malaria on markers of iron status in children: Implications for interpreting iron status in malaria-endemic communities. British Journal of Nutrition, 78(5), 751–760. [Crossref]
Doumas, B. T., & Watson, W. A. H. G. (1971). Clinical chemistry. Clinica Chimica Acta, 31, 87. [Crossref]
El Samani, F., Willett, W. C., & Ware, J. H. (1987). Nutritional and socio-demographic risk indicators of malaria in children under five: A cross-sectional study in a Sudanese rural community. Journal of Tropical Medicine and Hygiene, 90(2), 69–78.
Emmerson, T. (1989). Unique features of albumin: A brief review. Critical Care Medicine, 17(7), 690–694. [Crossref]
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry, 18(6), 499–502. [Crossref]
Goncalves, R. M., Scopel, K. K., Bastos, M. S., & Farreira, M. U. (2012). Cytokine balance in human malaria: Does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum? PLoS ONE, 7(9), e44394. [Crossref]
Hoffbrand, A. V., & Pettit, J. E. (2005). Postgraduate haematology (5th ed.). Blackwell Publishing.
Hoffbrand, A. V., Pettit, J. E., & Moss, P. A. H. (2006). Essential haematology (5th ed.). Blackwell Publishing.
Igbeneghu, C. (2005). Anaemia and malaria in children attending diagnostic laboratory in Ibadan. Nigeria Journal of Research in Bioscience, 1(1), 24–28.
Jain, N. C. (1986). Schalm's veterinary parasitology (4th ed.). Lea & Febiger.
Luzolo, A. L., & Ngoyi, D. M. (2019). Cerebral malaria. Brain Research Bulletin, 145, 53–58. [Crossref]
Macdonald, G. (1950). The analysis of malaria parasite rates in infants. Tropical Diseases Bulletin, 47(10), 915–938.
McKenzie, F. E., Prudhomme, W. A., Magill, A. J., Forney, J. R., Permpanich, B., Lucas, C., Gasser, R. A., & Wongsrichanalai, C. (2005). White blood cell counts and malaria. Journal of Infectious Diseases, 191(2), 323–330. [Crossref]
Mohanty, S., Mishra, S. K., Das, B. S., Satpathy, S. K., Mohanty, D., Patnaik, J. K., & Bose, T. K. (1992). Altered plasma lipid pattern in falciparum malaria. Annals of Tropical Medicine and Parasitology, 86(6), 601–606. [Crossref]
Nilsson-Ehle, I., & Nilsson-Ehle, P. (1990). Changes in plasma lipoproteins in acute malaria. Journal of Internal Medicine, 227(2), 151–155. [Crossref]
Nyakeriga, A. M., Troye-Blomberg, M., & Chemtai, A. K. (2004). Malaria and nutritional status in children living on the coast of Kenya. American Journal of Clinical Nutrition, 80(6), 1604–1610. [Crossref]
Ogbodo, S. O., Ogah, O., Obu, H. A., Shu, E. N., & Afiukwa, C. (2008). Lipid and lipoprotein levels in children with malaria parasitaemia. Current Pediatric Research, 12(1), 12–17.
Parola, P., Gazin, P., Patella, F., Badiaga, S., Delmont, J., & Brouqui, P. (2013). Hypertriglyceridemia as an indicator of the severity of falciparum malaria in returned travelers: A clinical retrospective study. Parasitology Research, 92(6), 464–466. [Crossref]
Price, R. N., Simpson, J. A., Nosten, F., Luxemburger, C., Hkirjaroen, ter Kuile, F., Chongsuphajaisiddhi, T., & White, N. J. (2001). Factors contributing to anaemia after uncomplicated falciparum malaria. American Journal of Tropical Medicine and Hygiene, 65(5), 614–622. [Crossref]
Reinheart, W. H., & Naggy, C. (1995). Albumin affects erythrocyte aggregation and sedimentation. European Journal of Clinical Investigation, 25(7), 523–528. [Crossref]
Renaudin, P., & Lombart, J. P. (1994). Anemia in infants less than 1 year old in Moundou, Chad: Prevalence and etiology. Medicine Tropicale, 54(4), 337–342.
Rosenthal, P. J. (2004). Cysteine proteases of malaria parasites. International Journal for Parasitology, 34(13–14), 1489–1499. [Crossref]
Sibmooh, N., Yamanont, P., Krudsood, S., Leowattana, W., Brittenham, G., Looareesuwan, S., & Udomsangpetch, R. (2004). Increased fluidity and oxidation of malarial lipoproteins: Relation with severity and induction of endothelial expression of adhesion molecules. Lipids in Health and Disease, 3, 15. [Crossref]
Tietz, N. W., Pruden, E. L., & Siggard-Anderson, O. (1986). Textbook of clinical chemistry. Saunders.
Valerian, L. K., Wendy, P. O., Richard, M., Fred, K. N., Godfrey, K., Enos, B., Tom, L., Marion, K. A., Fred, M., David, S., Ronald, H. G., & Kara, K. W. (2013). High prevalence of malaria parasitaemia and anaemia among hospitalized children in Rakai, Uganda. PLoS ONE, 8(12), e82455.
World Health Organization. (2010). World malaria report 2010. https://www.who.int/malaria/publications/world_malaria_report
World Health Organization Regional Office for the Eastern Mediterranean. (2007). Strategic plan for malaria control and elimination in the WHO Eastern Mediterranean Region (2006–2010).
World Health Organization. (2024). Malaria. https://www.who.int/news-room/fact-sheets/detail/malaria
Williams, T. N., Maitland, K., & Phelps, L. (1997). Plasmodium vivax: A cause of malnutrition in young children. QJM: An International Journal of Medicine, 90(12), 751–757. [Crossref]
Zuk, M., & McKean, K. A. (1996). Sex differences in parasite infections: Patterns and processes. International Journal for Parasitology, 26(10), 1009–1023. [Crossref]