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A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic

6 Aug 2008

Maria Victoria Valero

Citation: Menendez C, Bardajı´ A, Sigauque B, Romagosa C, Sanz S, et al. (2008). A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic. PLoS ONE 3(4): e1934.

Antimalarial drug resistance leads to an increase in morbidity and mortality, especially among children and pregnant women (1). Control of malaria in pregnancy, through prevention or treatment, may save lives and reduce complications in mothers and children (2).

Each year 50 million women become pregnant in areas where malaria is endemic, at least half of whom live in Africa (3,4). The effects of malaria during pregnancy include spontaneous abortion, preterm delivery, low birth weight, stillbirth, congenital infection, and maternal death. Selection of drugs for treatment of infected pregnant women, or for prevention in exposed populations is problematic, owing to resistance to established drugs and lack of pregnancy-specific safety and pharmacological data for new drugs (2,3). Due to the risk factors mentioned above, the prevention of malaria during pregnancy in highly endemic areas is a priority for public health services.

Strategies for the prevention of malaria in Africa include vector control with residual spraying, early diagnosis and prompt treatment. (Some countries are re-introducing DDT for residual spraying as a part of their overall control efforts.) Only an extremely small minority of people living in Africa take regular prophylactic drugs to reduce the risk of infection.

Intermittent preventive treatment (IPT) and insecticide treated nets (ITNs) have been introduced in recent years, but in many endemic regions their use is still limited. ITNs are associated with significant health benefits for both the mother and the newborn in sub-Saharan Africa (4). Intermittent preventive treatment of malaria in pregnancy (IPTp), which is administered at the time of antenatal clinic (ANC) visits, is recommended by WHO for preventing malaria during pregnancy (4,5). Unfortunately limited evidence exists about the use of both strategies combined.

Menendez et al carried out a randomised, double blind, placebo-controlled trial of IPTp in 1030 Mozambican pregnant women, in order to evaluate the safety and efficacy of two intermittent doses of sulphadoxine-pyrimethamine (SP) in women of all parities and regardless of HIV status, who had been given a long-lasting ITN (LLITN) through their antenatal clinic. The main outcome was a reduction in low birth weight.

The study showed that administering two IPTp-SP doses to women concurrently using LLITNs was safe and well tolerated. The intervention was associated with a moderate reduction in the incidence of clinical malaria during pregnancy, and with a statistically significant reduction in the prevalence of parasitaemia at delivery and at eight weeks postpartum (40% reduction, [95% CI, 7.40–61.20]; p = 0.020). Unfortunately, the differences were not significant for fetal birth outcomes (such as birth weight or prematurity), nor for maternal anaemia.

Malaria in pregnancy is a major concern and effective promoting and preventive actions are urgently required. We need further investigations to understand mechanisms, comprehensively designed studies to evaluate the safety and efficacy of malaria vaccines, and intervention research on the delivery of these strategies under health system conditions. However, health authorities must concentrate their preventive actions mainly on more vulnerable populations (pregnant women and children) as the main priority of malaria control policies.

The development of new drugs and a vaccine remains an urgent need. Research will require multi-centre trials in different areas. However, to quote the study authors, ‘In the meantime, efforts should be focused to promote the delivery of long-lasting ITNs as part of other routine ANC [antenatal care] health interventions.’

References

1. Lagerberg RE (2008). Malaria in pregnancy: a literature review. J Midwifery Women’s Health; 53(3):209-215. Available from: http://dx.doi.org/10.1016/j.jmwh.2008.02.012

2. Rogerson SJ, Menendez C (2006). Treatment and prevention of malaria in pregnancy: opportunities and challenges. Expert Rev Anti Infect Ther; 4(4):687-702. Available from: http://dx.doi.org/10.1586/14787210.4.4.687 (abstract only)

3. Barnes KI, Watkins WM, White NJ (2008). Antimalarial dosing regimens and drug resistance. Trends Parasitol; 24(3):127-134. Available from: http://dx.doi.org/10.1016/j.pt.2007.11.008

4. World Health Organization (WHO) (2004). A strategic framework for malaria prevention and control during pregnancy in the African region: report AFR/MAL/04/01. Brazzaville, Democratic Republic of Congo: WHO Regional Office for Africa. Available from: http://www.who.int/malaria/rbm/Attachment/20041004/malaria_pregnancy_str_framework.pdf

5. Lengeler C (2004). Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database Syst Rev, Issue 2. Available from: http://dx.doi.org/10.1002/14651858.CD000363.pub2 (abstract only)

2008 Menendez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Source

Title:
A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic.

Authors:
Menéndez C, Bardají A, Sigauque B, Romagosa C, Sanz S, Serra-Casas E, Macete E, Berenguera A, David C, Dobaño C, Naniche D, Mayor A, Ordi J, Mandomando I, Aponte JJ, Mabunda S, Alonso PL

References:
PLoS ONE 2008: Vol. 3 no. 4, pp. e1934

Abstract:
BACKGROUND: Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use. METHODS: 1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight. FINDINGS: Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was more than 90% in both groups. CONCLUSIONS: Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00209781.

PMID: 18398460
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