Evaluation of the effectiveness of antimalarial interventions during pregnancy in Blantyre, Malawi
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Due to an increased risk of malaria during pregnancy, WHO recommends a strategic framework for malaria prevention and control during pregnancy in areas of stable transmission in Africa such as Malawi. One of the central policies is intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). However, the emergence of SP resistance calls into question its effectiveness for IPTp. It has recently been demonstrated that 12 years after the withdrawal of chloroquine (CQ) use in Malawi, CQ susceptible malaria parasites now predominate and CQ is regaining its efficacy. To explore the potential role of CQ for the prevention of malaria during pregnancy, a randomized, controlled clinical trial of CQ chemoprophylaxis versus intermittent preventive therapy compared to standard IPTp with SP to prevent malaria in pregnancy in Blantyre, Malawi was conducted. The trial provided a platform to investigate the prevalence and incidence of malaria infection during pregnancy in three treatment arms namely CQ chemoprophylaxis, CQ-IPTp and SP-IPTp. Filter paper specimens from 240 patients (80 from each of the three treatment arms of the clinical trial) were used to determine and compare the incidence of malaria, the time to the first occurrence of malaria after treatment and compare baseline prevalence against the prevalence at delivery. A real-time PCR malaria detection assay technique was used to detect presence of malaria parasites from specimens collected at regular monthly visits and unscheduled sick visits from women who participated in the study and whenever they were ill. The occurrence of malaria infection among women receiving the three different interventions (CQ chemoprophylaxis, CQ-IPT and SP-IPT) was compared using Poisson regression. Kaplan-Meier survival analysis was used for overall comparison of time to the occurrence of malaria infection across the three treatment arms. McNemar test was used to compare the prevalence of malaria infection at baseline and at delivery in each treatment arm. The incidence of malaria infection were 1.98 (95% CI: 0.50, 8.04) per 100 person months in the CQ-IPTp arm and 0.34 (95% CI: 0.04, 3.33) per 100 person months in the CQ prophylaxis as compared to 0.99 per 100 person months in the standard SP-IPTp arm (p>0.05). No statistically significant difference was observed on pairwise comparison of the CQ prophylaxis arm and the CQ-IPTp interventions to the standard SP-IPTp. Mean time in months to the first occurrence of malaria infection (survival times in months) were 7.59 (95% CI: 7.38-7.78), 7.76 (95% CI: 7.67-7.86) and 7.60 (95% CI: 7.38-7.83) for the SP-IPTp, CQ-Prophylaxis and CQ-IPTp arms respectively and overall comparison by log rank did not show statistical significance (p>0.05). Whilst the CQ prophylaxis arm and the CQ-IPTp interventions reduced the prevalence of malaria infection to none at delivery, malaria parasitaemia was detected at delivery in the SP-IPTp arm. Nonetheless there was a significant difference (p<0.05) between the prevalence of parasitaemia at baseline and delivery in the SP-IPTp arm. This study shows non-inferiority of CQ-IPTp and CQ-prophylaxis over SP-IPTp for the prevention of pregnancy associated malaria. If these findings are validated in different settings, it could therefore imply that CQ-IPTp and CQ-prophylaxis could be re-introduced for control of malaria during pregnancy.