Karin Marie Plunkett
Biology 1615 Lab
Folic Acid Treatment of Zambian Children with Moderate to Severe
Malaria Anemia
The incidence of malaria anemia in children in Africa occurs frequently
enough that the medical personnel administering the drugs began to question the
efficacy of the concurrent administration of some of the medications. The question
that arose was whether or not it was beneficial to administer folic acid along with
the anti-malarial medications. In order to determine the value of the drug
combination, a randomized, placebo-controlled trial was set up and executed.
Materials and Methods:
The study was conducted in the southern province of Zambia and involved
children with moderate to severe malarial anemia. A major complication of
Plasmodium falciparum infection and morbidity and mortality in their youth is
anemia. The destruction of red cells (by either parasitic means or immune system
attach) is considered a primary cause of the anemia.
These patients were treated with either sulfadoxine/pyrimethamine (SP) or
atovaquone/proguanil (AP) along with either folic acid or placebo. There was some
evidence from previous studies preformed in African children that SP, when coadministered with folic acid, was less effective than when administered alone. This
trial was, in part, to determine if that was indeed the case.
A computer-generated randomization list was produced and a system for a
double blind study was established. The study was approved by the Tropical
Diseases Research Center in Ndola and monitored by an independent Data and
Safety Monitoring Board.
The children had to meet certain health, age and weight parameters to be
included in the study. They needed to be 6-119 months, have a blood film positive
for asexual forms of p. falciparum, fever or history of one within 24 hours, a packed
cell volume of 2-21%, and weigh 5 kg or more. Eliminated from the study were
subjects who could not sit or stand unsupported, were experiencing respiratory
distress, had an inability to take oral medications, exhibited signs of an additional
serious illness, or had received a blood transfusion within the past month.
Results:
The final results of this study were not as conclusive as was desired. The
study size was reduced due to secondary illnesses, death, and extreme levels of
anemia requiring administration of rescue treatments. Only 183 (72%) of the
original 255 patients who enrolled in the study were able to complete it.
Discussion:
To treat malaria, there is a need to eliminate parasitism and increase PCV
(packed cell volume). There is some evidence that demonstrates benefit in the
addition of iron supplementation along with PC or AP anti-parasitic drugs. When
administered concurrently with SP, folic acid has proven to be detrimental to
necessary parasite clearance in patients; however, some small benefit was present
when administered with AP.
In conclusion, it was determined that there is a statistically significant, yet
modest benefit to the administration of folic acid. The exception to that benefit is
when it is administered with SP. Folic acid ought to be avoided, at least in large
doses, when SP is used as the treatment of choice in a child with malaria.