Cardiovascular Disease
| Anemia | Kidney
Disease | Liver Disease | Central Nervous System Disorders | Diabetes Mellitus | Myasthenia
Gravis | Malaria and anaesthesia | Dermatitis | Pregnancy | HIV./AIDS
Malaria can
exacerbate/complicate pre-existing clinical conditions, adding to its morbidity and
mortality. In this regard, the following points should be kept in mind:
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Patients with these conditions should be
managed energetically to avoid any potential problems.
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Even P. vivax (or other milder types) can
lead to deterioration in the condition, even causing death.
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Since P. vivax and other milder types
generally do not cause any complications or death by themselves, one should be careful in
filling up the death certificates in these patients. In these cases, malaria can at the
most be sited as a contributory cause and not as a primary cause.
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Pre-existing problems may influence
treatment of malaria, especially the choice of antimalarials.
Pre-existing cardiovascular disease:
Patients with severe valvular obstruction, compromised ventricular function and other
conditions of cardiac decompensation may land in trouble on contracting malaria. In severe
falciparum malaria, the myocardial function is remarkably maintained and most patients
have an elevated cardiac index, with low systemic vascular resistance and low to normal
right and left sided filling pressures. However in patients with decompensated heart, the
high grade fever, tachycardia, hypoxemia, metabolic acidosis etc. associated with malaria
may add to the existing cardiac decompensation.
Case report: A 43 year old bank
executive, known case of severe aortic stenosis and claiming to be asymptomatic and not on
any treatment, presented with high grade fever with chills of 3 days duration and repeated
vomiting. On examination he had a temperature of 103.40F, heart rate of
120/min, blood pressure of 100/60 and dry tongue, his cardiac examination revealed harsh
systolic murmur in the aortic area and chest was clear. His blood smear was positive for
P. vivax malaria. He was first treated with anti emetics, tepid sponging and antipyretics
and after half an hour, chloroquine was administered. His vomiting continued and he was
unable to take orally and his blood pressure dropped to 90 mm systolic. He was started on
normal saline infusion that was given carefully in view of his aortic stenosis. After 40
minutes of the infusion, he developed mild cough and breathlessness and there were creps
in the bases of lungs . The infusion was immediately stopped (by then about 75 ml had
flowed in) and Inj. Fruscemide 20 mg was given intravenously. After 5 hours, his fever
settled down and he started feeling better. Antimalarials, antipyretics and anti-emetics
were continued. Next morning echocardiography was done and it confirmed the diagnosis of
severe aortic stenosis. That afternoon he again had fever of 1020F and was
treated with tepid sponging and antipyretics. By 8 p.m., his temperature was 99.80F
and as he was talking to his wife he complained of chest discomfort and suddenly he
collapsed. He was immediately shifted to the Intensive care unit and the monitor showed
ventricular fibrillation. He was immediately defibrillated and put on advanced life
support system. He died after 3 days.
Anti malarials in cardiovascular
disease: Chloroquine, artemisinin, pyrimethamine/ sulphadoxine, tetracyclines and
primaquine can be safely used in these patients. Quinine can also be used carefully.
Mefloquine and halofantrine are better avoided in patients with known cardiac illness.
Chloroquine: Oral chloroquine is
safe in therapeutic or prophylactic doses. If the therapeutic dose or a high dose are
administered too rapidly by parenteral route, it can cause significant cardiotoxicity.
Hypotension, vasodilation, myocardial suppression, ECG abnormalities and cardiac arrest
can occur. Treatment includes mechanical ventilation, adrenaline and diazepam. Concomitant
use of chloroquine with amiodarone should be avoided.
Quinine: At therapeutic doses,
quinine is relatively safe. Rapid intravenous administration may cause hypotension. Acute
overdosage can cause fatal dysrhythmias such as sinus arrest, junctional rhythms, A-V
block, ventricular tachycardia and fibrillation. Quinine may delay the absorption and
elevate the plasma levels of cardiac glycosides like digoxin. Quinine should not be used
concomitantly with amiodarone. Concomitant use with astemizole and terfenadine can also
increase the risk of ventricular arrhythmias.
Mefloquine: Mefloquine
should be used with extreme caution in patients suffering from cardiac conduction
diseases. Mefloquine has been shown to cause asymptomatic sinus bradycardia and other
conduction abnormalities e.g. prolongation of the QT interval. Patients who are on either
a beta-blocker or calcium channel blocker are at particular risk if there are signs of
sinus bradycardia and/or atrioventricular block. Cardiac arrest has been reported in a
patient receiving a single prophylactic dose of mefloquine while concomitantly taking
propranolol. There appears to be no interaction between ACE inhibitors and mefloquine*.
Halofantrine: Halofantrine
prolongs QT interval in a concentration dependent manner and it can result in ventricular
arrhythmias and even death. It is therefore contraindicated in patients with prolonged QT
interval and with drugs known to cause prolongation of QT interval.
Pre-existing
anemia: Anemia is a common problem in developing countries of Africa and Asia and
it is commonly due to helminthiasis and malnutrition. Malaria is also common in these
areas. Both vivax and falciparum malaria can exacerbate the anemia, specially causing
problems in pregnancy and in children. Also, blood transfusion for anemia may transmit
malaria. See anemia in P. falciparum malaria
Pre-existing
renal disease: Severe falciparum malaria can compromise renal blood flow by
sequestration and obstruction to the microcirculation, by hemolysis, by dehydration and
hypovolumia, by acidosis etc. Any of this could prove detrimental to patients with
pre-existing renal disease. Acute intrinsic renal impairment occurs during apparently
'uncomplicated' falciparum malaria in children.
Malaria has been reported in renal transplant recipients. Malaria should be considered in
the differential diagnosis of fever in transplant recipients who have received organs or
blood products from an area of endemic malaria.
The dose of quinine needs modification in
renal failure whenever S. creatinine is > 3mg%.
Chloroquine increases plasma cyclosporin
concentration and may increase the risk of toxicity.
Pre-existing
liver disease: Patients with hepatocellular failure due to cirrhosis etc. may
deteriorate if they contract malaria.
A case of malaria in a recipient of
orthotopic liver transplantation ahs been reported. The patient was found to have
Plasmodium ovale malaria during evaluation of a severe febrile illness. The infection was
traced to a platelet transfusion and responded to treatment with chloroquine. Risk factors
associated with the development of malaria infection are identifiable and should be
reviewed from the recipient and donor when possible. Routes of infection in the liver
transplant patient would include blood products, the organ itself, and resurgence of
latent infection. (Post-transfusion acquired malaria complicating orthotopic liver
transplantation. Talabiska DG, Komar MJ, Wytock DH, Rubin RA: Am J Gastroenterol 1996
Feb 91:2 376-9)
None of the antimalarial drugs have any
direct hepatotoxic effect. However, chloroquine is not advisable in patients with severe
hepatic insufficiency.
Pre-existing
C.N.S. Disease: Malaria and anti malarial drugs may pose problems in patients with
pre-existing C.N.S. disorders like dementia, epilepsy etc.
Severe P. falciparum infection,
dehydration, hyponatremia, high grade fever can lead to deterioration of patients having
pre-existing dementia.
Elderly patients and patients with
dementia contracting malaria may be prone for secondary infections like aspiration
bronchopneumonia
Chloroquine, quinine and mefloquine can
cause neuropsychiatric side effects. Chloroquine and mefloquine are better avoided in
patients with significant neuropsychiatric disorders.
Epilepsy:
There are some reports of chloroquine causing convulsions even in previously healthy
patients. Mefloquine is contraindicated in patients with a history of convulsions. Several
case reports of first-time seizures in patients taking mefloquine in prophylactic doses
have been reported. There have also been reports of mefloquine reducing the half-life and
lowering the blood levels of sodium valproate. This may be due to mefloquine accelerating
the hepatic metabolism of sodium valproate, because they are both metabolized by the same
hepatic enzyme system*.
Doxycyline does not affect epilepsy, but
may interact with some of the anti-convulsants. Carbamazepine, phenytoin and barbiturates
may shorten the half-life of doxycycline by up to 50% and lower mean serum levels by liver
enzyme induction, thus possibly compromising its therapeutic efficacy. The degree to which
the levels are affected is not clear. In theory, this means that the usual recommended
prophylactic dose of 100mg daily could be taken more frequently, probably twice daily.
However an exact recommendation cannot be made because there is limited experience with an
increased incidence of side-effects. Therefore epileptic patients not taking
carbamazepine, phenytoin and barbiturates can safely use doxycycline as malarial
prophylaxis. Patients taking the above drugs must by aware of the fact that the normal
dose of doxycycline may not provide adequate protection and increasing the dose may result
in an increased incidence of side-effects*.
Diabetes
Mellitus: Severe P. falciparum malaria can cause hypoglycemia and this fact should
be borne n mind in diabetics receiving insulin and/or oral hypoglycemic agents. Suitable
dosage adjustments may be needed.
Quinine has stimulatory effects on the
pancreatic beta cells and is known to cause severe hypoglycemia. Thereby it may potentiate
the effects of sulfonylureas.
In normal patients and in normal doses
chloroquine does not appear to cause increased pancreatic secretion of insulin and has no
effect on plasma glucose concentrations. Some studies suggest that in
non-insulin-dependent diabetes mellitus chloroquine may improve glucose tolerance,
possibly by decreased metabolic degradation of insulin rather than increased pancreatic
secretion*.
There is very limited evidence that
doxcycline occasionally increases the hypoglycemic effects of insulin and sulphonylureas.
Although there is no need to avoid concomitant use, patients must be aware of signs of
hypoglycemia and, if needed, the dose of hypoglycemic agent should by adjusted*.
It is unknown whether mefloquine
interacts with oral antidiabetic agents. Treatment doses of mefloquine have caused
hypoglycemia especially in children and pregnant women, but mefloquine apparently does not
stimulate the release of insulin. Patients should be made aware of the possibility and
should be able to reduce the hypoglycemic dose if necessary*.
The impact of the above on the control of
diabetes is unknown; it is therefore suggested that blood glucose be monitored even more
closely and that medication adjustments are made as required*.
Myasthenia
Gravis: Quinine decreases the excitability of the motor end-plate region so that
response to repetitive nerve stimulation and to acetyl choline are reduced. Quinine may
produce alarming respiratory distress and dysphagia in patients with myasthenia gravis.
Chloroquine also may increase the
symptoms of myasthenia gravis and reduce the effect of neostigmine and pyridostigmine.
Antimalarials and anaesthesia: Quinine
enhances the effect of neuromuscular blocking agents and opposes the actions of acetyl
choline esterase inhibitors.
Tetracycline also can produce
neuromuscular blockade.
Chloroquine also has interactions with
the neuromuscular blocking agents.
This may have implications in anaesthesia
and post operative recovery where these drugs are routinely used.
Dermatitis:
Concomitant use of chloroquine with gold salts and phenyl butazone should be avoided
because all the three can cause dermatitis
* The Journal of MODERN PHARMACY, Volume
5 no. 3, 1998 and Malaria Update 1997, a publication by the staff of the Medicines
Information Centre, Cape Town, S.A.
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