Age and immunity to malaria in pregnant women

Abstract

Malaria remains one of the major public health problems in the world. According to the World Health Organization, 40% of the world population live in malaria-endemic regions. With an annual morbidity of 300-500 million people per year the world over, it causes 1-3 million deaths each year, especially in children under 5 and pregnant women. Malaria during pregnancy is usually accompanied by poor pregnancy outcomes for both the mother and the baby, such as anaemia, abortions and low birth weight. Presently, there is no vaccine and control relies mainly on intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and the use of insecticide-treated bed nets (ITNs) as prescribed by the National Malaria Control Programme, though other drugs are still being used. Parasite and vector resistance to drugs and insecticide are on the rise, hence the urgent need for the development of a vaccine. The development of a vaccine requires an in depth understanding of immunity to the disease, especially in the vulnerable groups. Besides the well established parity effect on the susceptibility to malaria in pregnant women, an age effect has been reported. This study therefore sought to find out if the age effect is due to a difference in the immune status of the women. The specific objectives included: To determine the plasma total IgG levels to malarial extract antigen (MA), the ring erythrocyte surface antigen (RESA) and the circumsporozoite protein (CSP) in women at delivery. To study the association between antibody levels and age. To study the association between antibody levels and placental parasitaemia. A retrospective cross-sectional study was designed in which the plasma of 247 women were selected on the basis of age from several plasma samples previously collected under the ICIDR/HIRE malaria project (1996-2001). Available data included the age, number of pregnancies and outcome, the last menstrual period, the use of chemoprophylaxis and placental parasitaemias read from impression smears of the placentas collected at delivery. Plasma from the 247 women were used in indirect ELISA assays for total IgG to the antigens of interest. Data was analyzed using the following computer software: MS Excel 8.0 and Epi Info 6.04. Student’s t test was used to compare means between two groups and the Chi square test was used to compare proportions between the two groups. A confidence interval of 95% was considered for statistical significance. Results and discussion Of the 247 women selected, 108 were ≤ 20 and 139 were ≥25 years. The conception of age limits for the groups was based on two studies in Cameroon which independently reported age ≤ 20 and age ≤ 25 as risk factors for placental malaria. The mean age for each group was 18.4 and 29.9 years respectively. The use of chemoprophylaxis was reported by 83.4% of the women compared to 16.6% who reported no use. Also, fewer younger women reported the use of chemoprophylaxis than older women (75% compared to 89.2%, p=0.003). Age did not influence levels of antibodies to MA (r= -0.06, p> 0.05) and to RESA (r= -0.005, p> 0.05). On the other hand, anti-CSP antibody levels increased with age (r= 0.21, p< 0.001). This could explain why younger women are more susceptible to malaria as these antibodies protect against re-infections. Antibodies against asexual blood stage antigens are essential in controlling parasitaemia, however in this study, no association was found between anti-MA antibodies and placental parasitaemia (r=0.07, p>0.05), as well as between anti-RESA antibody levels and placental parasitaemia (r= -0.07, p>0.05). A positive correlation was found between anti-CSP antibody levels and placental parasitaemia. The positive correlation obtained in this study could be explained by the fact that infected women would produce high levels of antibodies, and high antibody levels would rather reflect infection than protection, as antibodies to CSP are not effective against asexual blood-stage parasites. Conclusions From the above findings, the following conclusions can be drawn: 1. There is no association between age and anti-MA antibody levels as well between age and anti-RESA antibody levels. 2. Anti-CSP antibodies increased with age, and can possibly explain why younger women are more susceptible to malaria, as anti-CSP antibodies protect against re-infection. 3. There is no association between antibodies to asexual blood stage antigens tested (MA and RESA) and placental parasitaemia. 4. There is a positive correlation between anti-CSP antibodies and placental parasitaemia. These antibodies are indicative of infection and do not play a role in parasite clearance. Recommendations Based on the conclusions arrived at, the following recommendations are made: 1. CSP be considered as a vaccine candidate in a cocktail vaccine for pregnant women as this would prevent re-infection amongst the younger women. 2. Similar studies should be carried out using different asexual blood stage antigens to evaluate their role in parasite clearance, hence their potential use as vaccine candidates. 3. Longitudinal studies should be carried out to evaluate the kinetics of anti-MA and anti-RESA antibodies during pregnancy to better assess the benefit of these antibodies on the level of parasitaemia.