Total serum calcium levels were estimated in 60 adult patients with malaria to know the prevalence of hypocat:emia in different types of malaria and its clinical implications. As hypocalcemia is known to cause Q - Tc interval prolongation, electrocardiograms were obtained in all patients with low calcium levels. Twenty seven (4S@Mo) patients with malaria had hypocalcemia. Majority (88.24%) of the complicated malaria patients had hypocalcemia as against uncomplicated malaria (27.91%). Mean calcium levels were significantly lower in complicated malaria (7.4 +/-0.98 mg/dl) when compared to uncomplicated malaria (8.40+/-.44 mg/dl). There was an inverse relation between calcium levels and parasite load (P
Key words Calcium - hypocalcemia - malaria - Q- Tc prolongation - quinine toxicity
Malaria is an important cause of mortality and morbidity in the tropics1. With the resurgence of malaria in Mangalore, a coastal city of Karnataka, as many as 20,000 people suffered from m'!aria during the year 1995-19962. While we were treating cases of malaria, we noticed tetany in a patient with malaria who was confirmed to have hypocalcemia. Since then we started noting hypocalcemia as a significant biochemical abnormality in malaria. Although there is a mention of hypocalcemia as a finding in cerebral malaria3, there is no mention of its prevalence and clinical implications. There are reports of hypocalcemia in bacteremic patients4 and intensive care unit patients5. Hypocalcemia is known to produce Q- Tc prolongation in electrocardiograms6. We also noted prolonged Q- Tc in patients with malaria and hypocalcemia. This prompted us to undertake a study to know the prevalence of hypocalcemia in different types of malaria; measure Q- Tc interval in the ECGs of patients with malaria for possible correlation with hypocalcemia and see whether calcium levels can be of prognostic value in malaria.
Material & Methods
Sixty consecutive adult patients of either sex admitted to the medical wards of Kasturba Medical College Hospital, Mangalore with a' diagnosis of malaria during the period October 1995 - June 1996 were included in the present study. Malaria was diagnosed by positive blood smear examination or by positive report on Acridine Orange - Quantitative Buffy Coast examination (AO-QBC)'. Parasite load was determined using a plus (+) system starting from + to + + + +8. Serum total calcium was estimated in all these patients. Serum albumin levels were checked in patients with malnutrition or hepatic dysfunction and calcium corrected for the albumin value. Those who had low calcium levels (serum calcium
Statistical methods : All comparative data were analysed by normal deviate test or z test and correlative data were analysed by Spearman's rank correlation coefficient.
Sixty cases of malaria were studied of which 27 (45%) were found to have low calcium levels. Fifteen out of 17 (88.24%) complicated cases had hypocalcemia as against 12 out of 43 (27.91%) uncomplicated cases (P
ECGs obtained in 27 patients showed prolonged Q-Tc in 93 per cent of complicated malaria patients with a mean of 0.500.05 sec as against 50 per cent in uncomplicated malaria cases with a mean Q- Tc of 0.43+/- 0.5 sec. The Fig. shows relationship between degree of hypocalcemia and Q-Tc prolongation (P
Five patients with hypocalcemia had clinical features of tetany such as carpopedal spasm (3), fasciculations (1), Chvostek's sign (1). There were 17 complicated malaria cases of which 12 had cerebral malaria, 10 had renal failure, 5 had hepatitis, 2 had hyperpyrexia. Except for those with hyperpyrexia, all had low calcium levels and Q-Tc interval was prolonged in all patients except 2 patients with cerebral malaria.
Three patients died due to severe malaria and multiorgan failure of which 2 had hypocalcemia. All the three had prolonged Q-Tc and developed hypotension, bradycardia and heart block after quinine in the dose of 10 mg/kg body weight. Two other patients who did not have serum calcium levels estimated, died of broad QRS tachycardia which transiently responded to calcium gluconate. However, the effect was not long lasting. Both these patients had tetany and prolonged Q - Tc in ECGs. They had received the conventional dose of parenteral quinine (20 mg/kg quinine loading dose followed by 10 mg/ kg wt 8th hourly as infusions). From then on, those with prolonged Q-Tc were given three fourths of the dose of quinine and there was no cardiovascular death after that.
None of the patients with hypocalcemia had hypoglycemia on presentation. However, 7 patients developed hypoglycemia after quinine therapy. There was no relationship between serum calcium and blood glucose levels. However, blood glucose was done only in 17 complicated malaria cases and 8 uncomplicated malaria cases with low calcium levels. Only 2 patients received blood transfusions. But serum calcium levels were measured before transfusion. All the patients with low calcium levels were treated with intravenous 10 ml calcium gluconate 8th hourly followed by oral calcium supplements. In spite of parenteral calcium supplements serum calcium levels remained low till parasite clearance. Return of calcium levels to normal coincieded with clinical recovery and parasite clearance.
The results of our study indicate that hypocalcemia is a feature of complicated malaria. Although there is a mention of hypocalcemia as a feature of complicated malaria3, there is no literature on its prevalence and clinical implications. Similarly there have been reports of Q - Tc prolongation12 and sudden deaths"3 in malaria. But the exact cause for Q - Tc prolongation was not known. There have been several reports on correlation between hypocalcemia and QTc prolongation6'1. We have also found a good correlation between hypocalcemia and Q - Tc prolongation. High prevalence of hypocalcemia has been reported in bacteremic patients (37.3%)4 and in patients in intensive care unit (77.5%)5. Hypotension, cardiac insufficiency, arrhythmias such as bradycardia, ventricular fibrillation, prolonged Q-Tc are the reported manifestations of hypocalcemia in the critically ill. Our patients who died, had some of these features. Tetany was observed rarely (only in 5 patients) in spite of low serum calcium levels probably because all these patients were on quinine, which is known to suppress tetany'6.
Our observations regarding quinine dosage reduction in patients with prolonged Q - Tc is worth noting, since quinine/quinidine can prolong Q - Tc". Controlled trials are needed to see the effect of half or three fourth of the recommended dose of quinine in patients with prolonged Q - Tc.
Hypocalcemia in malaria was found to correlate with heavy parasitemia, complications and Q-Tc prolongation. Hence hypocalcemia in malaria may be a biochemical marker for complications. It was found to return to normal with clinical recovery, parasite reduction and return of Q-Tc interval to normal. Hence serum calcium levels may be of prognostic value.
The exact cause of hypocalcemia in malaria could not be ascertained. However, renal failure, associated hypomagnesemia, alkalosis and parathyroid failure could have contributed. Since our patients showed transient improvement following intravenous calcium supplements, coexistence of magnesium deficiency needs to be considered. Further studies in this direction with serum phosphorous, alkaline phosphatase and magnesium levels are warranted.
In conclusion, hypocalcemia is a feature of severe/ complicated malaria as it had a good correlation with parasite load and complications. It has a prognostic value in malaria, as recovery from malaria was associated with return of serum calcium levels to normal. Although there was a statistical correlation between hypocalcemia and Q - Tc prolongation further studies are warranted to rule out other causes of Q - Tc prolongation. Q - Tc prolongation in malaria could be a risk factor for quinine cardiotoxicity and controlled trials with reduced quinine dosage are warranted in patients with prolonged Q - Tc to confirm quinine dosage reduction in such patients.
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M.R. Adhikari Prabha, Pratibha Pereira, Nityananda Chowta & B.M. Hegde Department of Medicine, Kasturba Medical College, Mangalore
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