THE EFFECT OF MEFLOQUINE CHEMOPROPHYLAXIS ON THE OUTCOME OF PREGNANCY IN WOMEN OF LOW AND HIGH PARITY IN ZARIA, NIGERIA
THE EFFECT OF MEFLOQUINE CHEMOPROPHYLAXIS ON THE OUTCOME OF PREGNANCY IN WOMEN OF LOW AND HIGH PARITY IN ZARIA, NIGERIA
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Date
2008-07
Authors
MAIHA, BILKISU BELLO
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Abstract
Malaria accounts for 25% -70% of infant, 30% of under- five and 7% -11% of maternal
mortality in Nigeria. The World Health organization recommended malarial drug
prophylaxis for pregnant women in malaria endemic areas to prevent the adverse
consequences of malaria in pregnancy. However, the development of resistance by the
plasmodium to drugs has led to the failure of such interventions. The current
recommended drug regimen for chemoprophylaxis of malaria in pregnancy is two
curative doses of sulfadoxine–pyrimethamine (SP), given during the second and third
trimesters, but there are reports of resistance to SP in four of the six geopolitical zones of
Nigeria. In view of this development, alternative regimens for prevention of malaria in
pregnancy have to be investigated to help in policy formulation. This study was designed
to study the effect of mefloquine chemoprophylaxis on pregnant women of low and high
parity in Zaria, Nigeria. A single blind study involving 985 women in the second
trimester of pregnancy randomly distributed, 508 (57.6%) to the mefloquine and 477
(48.4%) to the placebo group, with an average age of 23.77 ± 9.21 was carried out. The
mefloquine group received 750mg mefloquine at enrolment and 250mg weekly until
delivery while the placebo group received placebo tablets. The effect of mefloquine on
haematocrit levels, parasitemia, delivery outcome, anthropometric measurement of
babies, placental weight and placental pathology were assessed. Student t- test was used
to compare means and Chi-square test or Fisher’s exact test was used to compare
proportions. Differences were considered significant at 95%. The placebo group had
significantly more women with parasitemia (p<0.0001) at enrolment and at weeks 4, and
9 (p<0.05, p<0.005 respectively), and more reports of fever. None of the women in the
mefloquine group developed clinical malaria during the study. The mefloquine group had
significantly higher PCV values during the second (p=0.05) and third months of the study
(p=0.006). The high parity mefloquine group also had significantly higher PCV than high
parity placebo group at second and third months (p=0.05, p=0.027 respectively). The
mefloquine group had a significantly better delivery outcome than the placebo group
(p=0.027) with the placebo group having more stillbirths. Incidence and type of
congenital malformations (1%) was similar in both groups. High parity mefloquine group
had significantly heavier babies (p<0.05), larger OFC (p<0.05), and heavier female
babies (p=0.022). The mefloquine group also had heavier (p=0.011) females when all
parities were combined. Sex had no effect on birth weight within the mefloquine group,
while males were heavier than females (p=0.029) in the placebo group. Histopathological
findings showed that the high parity groups were associated with increased incidence of
calcium, fibrin, malaria pigment deposition and malaria parasites in placental tissues. The
incidence of nausea was significantly higher in week 4 (p<0.05) while vomiting was
significantly different in week 1, 2 and 4 (p<0.05) for the mefloquine group. There was
no significant difference for diarrhoea and pruritus but dizziness was significantly more
in the placebo group at week 9 and 16 (p<0.05). In conclusion, mefloquine
chemoprophylaxis was well tolerated by pregnant women with self limiting adverse
effects. They were protected from clinical malaria, had an improvement in haematocrit
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levels with an increase in birthweight in the high parity group. Mefloquine was found to
be effective for antimalarial prophylaxis in the second half of pregnancy and can be used
as an alternative to SP for protection against malaria in pregnancy.
Description
A THESIS SUBMITTED TO THE POST GRADUATE SCHOOL,
AHMADU BELLO UNIVERSITY, ZARIA, IN PARTIAL
FULFILMENT FOR THE AWARD OF DOCTORATE DEGREE IN
PHARMACOLOGY
Ph.D/PHARM.SCI/900/9001/1993/94
Ph.D/PHARM.SCI/56850/2005-06
DEPARTMENT OF PHARMACOLOGY AND CLINICAL
PHARMACY
FACULTY OF PHARMACEUTICAL SCIENCES
AHMADU BELLO UNIVERSITY, ZARIA.
JULY, 2008
Keywords
EFFECT,, MEFLOQUINE,, CHEMOPROPHYLAXIS, PREGNANCY,, WOMEN,, LOW,, HIGH,, PARITY,, ZARIA,, NIGERIA.