THE EFFECT OF MEFLOQUINE CHEMOPROPHYLAXIS ON THE OUTCOME OF PREGNANCY IN WOMEN OF LOW AND HIGH PARITY IN NIGERIA
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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 9 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 10 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.
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