Changes in Serum Glucose and Triacylglycerol Levels Induced by the Co-administration of Two Different Types of Antimalarial Drugs among Some Plasmodium falciparum Malarial Patients in Edo-delta Region of Nigeria
The aim of study was to show the changes in serum glucose and TAG levels in patients receiving anti-malarial treatment as well as changes caused by therapeutic drug type. One hundred individuals were investigated comprising of 40 apparently healthy control individuals, 40 malarial infected patients receiving either one or two types of anti malarial treatment and 20 P. falciparum infected patients but yet to be treated, using standard procedures for Glucose and Triaclyglycerol estimation. Results showed significantly reduced (p<0.05) serum glucose (4.02±0.80 mmol L-1) and TAG (1.27±0.54 mmol L-1) in malarial infection when compared with the control values (5.22±0.67 mmol L-1 and 1.50±0.56 mmol L-1) from apparently healthy subjects and intake of anti-malarial drugs raised serum glucose (4.80±0.60 mmol L-1) when compared with values for those infected but yet to be treated (4.02±0.80 mmol L-1), although this value was still lower than that for the healthy control subjects. However anti-malarial treatment increased serum TAG (1.67±0.81 mmol L-1) even above the level observed for the healthy subjects (1.50±0.56 mmol L-1). Glucose (4.72±0. 52 mmol L-1) and TAG (1. 97±0.92 mmol L-1) levels were higher in patients receiving two different types of anti-malarial drugs (artesunate/coartem, lonart/camoquin, artesunate/fansider) compared with those receiving only one type of anti-malarial drug (artesunate, coartem, camoquin, lonart). The results suggest that malarial infection significantly (p<0.05) reduces blood glucose and TAG levels but treatment with especially two different types of anti-malarial drug raised blood glucose and TAG levels. Combination of two different types of anti-malarial drug in the treatment of malarial infection could significantly improve the hypoglycemic risk but its highly exaggerated influence on serum TAG may be worrisome.
to cite this article:
I. Onyesom and J.E. Agho, 2011. Changes in Serum Glucose and Triacylglycerol Levels Induced by the Co-administration of Two Different Types of Antimalarial Drugs among Some Plasmodium falciparum Malarial Patients in Edo-delta Region of Nigeria. Asian Journal of Scientific Research, 4: 78-83.
Received: April 08, 2010;
Accepted: June 29, 2010;
Published: October 12, 2010
Malarial is a vector-borne infectious disease caused by protozoan parasite
which has overtime been a point of concern and in recent times received a lot
of attention due to its widespread nature in tropical and subtropical
regions, including parts of America, Asia and Africa. Each year, there are approximately
515 million cases of malarial, killing between one and three million people,
the majority of whom are young children in sub-Saharan Africa (Snow
et al., 2005).
The disease is caused by protozoan parasite of genus Plasmodium with
the most infectious form caused by P. falciparum. The primary host of
the parasite is the female Anopheles mosquito and has infected people
for over 50,000 years (Joy et al., 2003). Close
relative of the human malarial parasite remain common in chimpanzees (Escalante
et al., 1998). Malaria is presently endemic in a broad band around the
equator; however, it is in sub-Saharan Africa where 85-90% of malaria fatalities
occur. Malaria is common in rural areas and pregnant women are most especially
vulnerable. Despite efforts to reduce transmission and increase treatment, there
have been little changes in infection rate in areas at risk of this disease
since 1992 (Hay et al., 2004). Indeed, if the
prevalence of malaria stays on its present upward course, the death rate could
double in the next twenty years (Breman, 2001). No vaccine
is currently available for malaria and preventive drugs must be taken continuously
to reduce the risk of infection (Hull, 2006).
Treatment of malaria involves supportive measures as well as specific anti-malarial
drugs. Chemotherapy is the primary means of treating protozoan infections. Successful
chemotherapy depends largely on the ability to exploit metabolic differences
between the pathogens and the host. A number of drugs used as prophylaxis against
or treatment for malaria have chemical significant metabolic side-effects. Of
these, hypoglycemia resulting from quinine administration is one of the most
important (Warrel et al., 1990). Quinidine the
diastereoisomer of quinine can also cause this complication. The 4-aninoquinoline
chloroquine is known to influence glucose metabolism in ways which could lower
blood glucose concentration (Smith et al., 1987).
Recently quinoline methanol, mefloquine has been shown to reduce plasma glucose
concentration during conventional prophylactic course in healthy young adults
(Davis et al., 1996). In all these situations,
raised serum or plasma insulin concentration has been observed on which maintenance
of appropriate blood glucose level is dependent. Observation has also shown
that blood lipid of level which triacylglycerol (TAG) is a basic constituent
is related to the amount of serum insulin, though little attention has been
paid to the effect of anti-malarial drugs on serum lipid. This study seeks to
show the changes in serum glucose and TAG levels in patients receiving anti-malarial
treatment as well as changes caused by therapeutic drug type whether one or
two different anti-malarial drug treatment.
MATERIALS AND METHODS
Subjects: A total of 100 subjects (50 males and 50 females) were used
for this study. Forty of the subjects were P. falciparum malarial infected
patients receiving either one type or two different types of anti-malarial drugs
of either artesunate, coartem, carmoquine or lonart. Forty apparently healthy
individuals and 20 other individuals infected with P. falciparum but
yet to be treated were included as control groups. Informed verbal consent was
sought and obtained from the volunteers (or guardians) whose ages range from
5-60 years who were from Faith medical center Benin and University Health center
Delta State University Abraka Delta state. The study was between March 2009
and September 2009.
Sample collection: Three specimen bottles were used to collect blood
specimen from each subject. Fluoride oxalate bottles for blood glucose determination,
plain sterile bottles for serum triacylglycerol (TAG) estimation, EDTA (ethylene
diamine tetra acetic acid) bottles for malaria parasite count. Blood samples
were collected by clean venepuncture technique from the antecubital fossa into
already labelled bottles with undue pressure on either the arm or the plunger
of the syringe. Samples in the fluoride oxalate bottles were tested immediately
for glucose while samples in the plain tube were allowed to clot and then centrifuged
at 1200 xg for 5 min at room temperature (28-31°C) to obtain sera samples
for triacylglycerol determination. Samples in EDTA anticoagulant bottles were
tested immediately for malarial parasite after staining the thick film with
Specimen Analysis: The malaria parasite count was done by examining a thick
blood film stained with Giemsa stain (Cheesbrough, 1998).
Blood glucose estimation was carried out using the glucose oxidase method (Berham
and Trinder, 1972). Triacylglycerol estimation was done by the enzymatic
method (Carstensen, 1985) using the reflotron analyzer.
Statistics: Data were analyzed using analysis of variance (ANOVA) and correlation performed by SPSS version 16 statistical software. Results were expressed as Mean±Standard Deviation (±SD).
Malaria infection significantly reduced (p<0.05) serum glucose and TAG when compared with the control values obtained from the apparently healthy subjects. Intake of anti-malarial drugs increased serum glucose when compared with the values for those infected but yet to be treated, but still lower than the healthy control level. Serum TAG for malarial infected patients receiving treatment was highest when compared with those infected without treatment and the healthy subjects.
Serum glucose and TAG levels were higher for the female subjects irrespective of the groups but malaria infected male patients receiving anti-malaria treatment had higher amount of serum TAG. There are no significant age-related changes in serum glucose and TAG but overall, effect of malarial infection on the reduction in serum glucose and TAG was most severe among those between 0-15 years:
||Artesunate: It is active component is artemesinin (dehyroartemesinin).
Reduces parasite gematocytes transmission and Inhibits protein synthesis
via DNA replication in the parasite
||Coartem: It is active components include artemether
and halofantrine- forms cytotoxic complexes with faritoporphyrin IX that
causes plasmodia membrane damage
||Lonart: It contains arthemether and halofantrine. Has
same action as coartem
||Fansider: Sulfadoxine (500 mg) and pyrimethamine (20 mg):
It inhibits dehydrofolate reductase in the parasite thus preventing the
biosynthesis of purines and pyrimidines, halting DNA synthesis, cell division
and reproduction of parasite
||Camoquine: Amodiaquine HCl (200 mg) (4 aminoquinolin):
It controls the conversion of toxic heam to hemozion by inhibiting the
biocrystallization of hemozoin thus poisoning the parasite through excess
levels of to toxicity and interfere with parasite nucleic acids
Glucose and TAG levels were higher in patients receiving two different types of anti-malarial drugs compared with those receiving only one types of anti-malaria drugs. These values were still lower than those for the non-infected healthy subjects but higher than the levels found among the infected subjects, yet to be treated.
The TAG value for those receiving one type or two different types of anti-malarial drugs was higher compared with either the healthy control values or the value for the malarial infected patients who are yet to be treated (Table 1).
||Changes in Glucose and TAG levels among P. falciparum infected
patients receiving one or two different types of antimalarial drugs
|Results are expressed as a Mean±SD
The results of this study show reduction in serum glucose levels in patients
receiving anti-malarial treatment (p>0.05) and in malarial infected patients
yet to be treated (p<0.05), when compared with the level obtained from the
healthy control subjects (Table 2). Malarial infected patients
(children between 0-15 years) had the highest considerable risk of hypoglycemia.
The co-administration of two different types of anti-malarial drugs appears
to significantly reduce the risk of hypoglycemia when compared with the administration
of one type of anti-malaria drug (Table 1). Reduction in blood
glucose level and subsequently, hypoglycemia is a well recognized complications
of Plasmodium falciparum malaria and its treatment (White
et al., 1983). This has been observed to be particularly common among
children, pregnant women and patients with severe malaria and hyper parasitaemia.
Plasmodium falciparum induced reduction in blood glucose could be due
to the invasion of the liver cells by the malarialparasite which can cause organ
congestion, sinusoidal blockage and inflammation of pancreatic cells (Jarike
et al., 2002), leading to increased intracellular insulin, accumulation
and slow receptor recycling (Herbert, 2002).
Malarial infected patients receiving anti-malarial drug had increased serum
TAG but the level for those yet to be treated was lower when compared with the
value for the non-infected (control) subjects (Table 2). These
findings are consistent with earlier reports (Miller et
al., 2002), although there are claims of higher level of lipids in malaria
infected patients (Maegraith, 1981) based on the fact
that Plasmodium genome contains gene encoding enzymes of phosphohpids
metabolism allowing de novo synthesis of phosphatidylcholine via the
kneddy pathway necessitating only uptake of a small amount of choline molecule
from the host (Maegraith, 1981). However, explanation
for the observed lower concentration of TAG level in malarial infected patients
is based on the findings of higher requirement of lipids for the growth of the
parasite which de novo synthesis by the parasite might not meet completely.
Incidentally, lipids are synthesized in the liver which happens to be the major
site for Plasmodium infection (Vial et al.,
2003) and this raises claims to the relationship between lipid synthesis
and Plasmodium infection in the liver.
|| Levels of glucose and TAG in malarial infected subjects
|Results are presented as Mean±SD. M: Male, F: Female
The augmentational utilization of host nutrients by the Plasmodium parasite
could contribute to the observed decrease is serum TAG for malaria infected
patients. Serum TAG level was evidently higher among the group of malarial infected
patients receiving anti-malarial drug treatment. Anti-malarial inhibit parasite
action and promote parasite clearance and these reduce the demand on blood lipids
causing an increase in the mobilization of lipids to compensate for the energy
loss due to parasite activities (Harris, 2006).
Treatment with two different types of anti-malarial drugs increased both serum
glucose and TAG more than the level induced by one type of anti-malarial drug
(Table 1). The increase in serum glucose induced by the one
type of anti-malarial drug was higher when compared with the amount obtained
for the infected patients yet to receive treatment, but lower than the values
for the healthy (control) subjects. However, for TAG the level induced by either
one or two different types of anti-malarial drug was higher than the TAG concentration
for either healthy individuals or malarial infected patients yet to receive
treatment. Previous studies have shown that treatment with one type of anti-malaria
drug such as 4-aminoquinoline raises blood glucose concentration (Smith
et al., 1987) when compared with those not being treated, hence anti-malarial
treated patients who develop hypoglycemia are rare (Fisher,
1983). Chemotherapeutic-induced increase in blood glucose concentration
could be based on the influence of some anti-malarial drugs on insulin related
activities and glucose homeostasis (Cynober et al.,
1987). The quinine and quinidin a cinchonal alkaloid are known to increase
insulin secretion by blocking ATP-sensitive potassium (K+ ATP) channel
in pancreatic beta cells (Fatherazi and Cook, 1991).
Combination of two different types of anti-malarial drug in the treatment of malarial infection could significantly improve the hypoglycaemic risk but its highly exaggerated influence on serum TAG may be worrisome, especially now that TAG is seriously implicated as a single risk factor of cardiovascular disorder. Post treatment data are therefore required to provide more understanding in order to better advise health care providers.
1: Berham, D. and P. Trinder, 1972. In vitro determination of glucose in blood serum and plasma. Analyst, 77: 142-146.
2: Breman, J.G., 2001. The ears of the hippopotamus : Manifestations, determinants and extimate of the malaria burden. Am. J. Trop. Med. Hyg., 64: 1-11.
Direct Link |
3: Carstensen, C.A., 1985. Test for quantitative determination of triglycerides in blood, serum or plasma with reflotron. J. Clin. Chem. Clin. Biochem., 30: 608-608.
4: Cheesbrough, M., 1998. Laboratory Diagnosis of Malaria Parasite: District Laboratory Practice in Tropical Countries. Cambridge University Press, Cambridge, UK
5: Cynober, L., C. Aussel, N. Vaubourdolle, J. Agneray and O.G. Ekindjan, 1987. Modulation of insulin action on 2-deoxyglucose uptake by chloroquine in rich embryo fibroblast. Diabetes, 36: 27-32.
6: Davis, T.M.E., L.G. Dembo, S.A. Kaye-Eddie, B.J. Hawitte, R.G. Hislop and K.T. Bathy, 1996. Neurological, cardiovascular and metabolic effects of mefloquine in healthy volunteers: A double-blind, placebo-controlled trial. Braz. J. Clin. Pharmacol., 42: 415-421.
Direct Link |
7: Herbert, M.G., 2002. Parasite Metabolism and Life Cycle in the Liver. In: Essential Malariology, Warrell, D.A. and H.M. Gilles (Eds.). 4th Edn., Arnold, London, UK., pp: 1-34
8: Escalante, A.A., D.E. Freland, W.E. Collins and A.A. Lal, 1998. The evolution of primate malarial parasite based on the gene encoding cytochrome D from the linear mitochrondrial genome. Proc. Natl. Acad. Sci. USA., 95: 8124-8129.
Direct Link |
9: Fatherazi, S. and D.L. Cook, 1991. Specificity of tetraethylammonium and quinine for three potassium (K+) channels in insulin-secreting cells. J. Membr. Biol., 120: 105-114.
Direct Link |
10: Fisher, C.S., 1983. Acidosis and hypoglycemia in malaria. Braz. Med. J., 286: 1261-1269.
11: Hay, S.I., C.A. Guerra, A.J. Tatem, A.M. Noor and R.B. Snow, 2004. The global distribution and population at risk of malaria: Past, present and future. Lancet Infect. Dis., 4: 327-336.
PubMed | Direct Link |
12: Jarike, A.E., E.E. Emuveyon and S.F. Idogun, 2002. Pitfalls in the interpretation of liver parenchymal and membranous enzyme results. Pre-clinical P. falciparum malaria in the Nigerian environment. Nig. J. Clin. Med., 10: 21-27.
13: Joy, A.D., X. Feng, J. Mu, T. Furuya, K. Chotivanich and A. Kretti et al., 2003. Early origin and recent expansion of Plasmodium falciparum. Science, 300: 318-321.
Direct Link |
14: Maegraith, B., 1981. Aspects of the pathogenesis of malaria. Southwest Asian J. Trop. Med. Pub. Health, 12: 251-267.
15: Miller, L.H., D.I. Baruch, K. Maresh and O.K. Doumbo, 2002. The pathogene basis of malarial. Nature, 415: 673-679.
Direct Link |
16: Smith, G.D., T.A.S. Amos, R. Mawler and T.J. Peters, 1987. Effect of chloroquine on insulin and glucose homestasis in normal subjects and patients with non-insulin dependent diabeties mellitus. Br. Med. J., 294: 465-467.
17: Snow, R.W., C.A. Gurra, A.M. Noor, I.T. Mymt and S.I. Hay, 2005. The global distribution of clinical episode of plasmodium falciparum malaria. Nature, 434: 214-217.
Direct Link |
18: Harris, R.A., 2006. Major Metabolic Pathray and their Control. In: Text Book on Biochemistry with Clinical Correlation, Devlin, T.M. (Ed.). 6th Edn., Wiley-Liss, USA., pp: 582-634
19: Warrel, D.A., M.E. Molyneux and P.F. Beasles, 1990. Severe and complicated malaria. Trans. R. Soc. Trop. Med. Hyg., 84: 1-65.
20: White, N.J. D.A. Warrel and P. Chanthavanch, 1983. Severe hypoglyceamia and hyper insulinemia in falciparum malaria. N. Engl. J. Med., 309: 61-66.
Direct Link |
21: Vial, H.J., P. Eldin, A.G.M. Tierliers and J.J. ven Hellemond, 2003. Phospholipids in parasite protozoa. Mol. Biochem. Parasitol., 126: 143-153.
22: Hull, K., 2006. Malaria: Fever war. PBS Documentry. http://www.amazon.com/Malaria-Fever-Artist-Not-Provided/dp/B000EOTV48.