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

Clara Menéndez, Azucena Bardají, Betuel Sigauque, Cleofé Romagosa, Sergi Sanz, Elisa Serra-Casas, Eusebio Macete, Anna Berenguera, Catarina David, Carlota Dobaño, Denise Naniche, Alfredo Mayor, Jaume Ordi, Inacio Mandomando, John J Aponte, Samuel Mabunda, Pedro L Alonso, Clara Menéndez, Azucena Bardají, Betuel Sigauque, Cleofé Romagosa, Sergi Sanz, Elisa Serra-Casas, Eusebio Macete, Anna Berenguera, Catarina David, Carlota Dobaño, Denise Naniche, Alfredo Mayor, Jaume Ordi, Inacio Mandomando, John J Aponte, Samuel Mabunda, Pedro L Alonso

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Trial profile
Figure 1. Trial profile
There were 3 and 7 twins births in the SP and placebo groups respectively. There was one triplet birth in the SP Group.* sulphadoxine-pyrimethamine ** 1 woman in the SP group and 2 in the placebo group had a miscarriage before receiving dose 1
Figure 2. Intention to treat cohort.
Figure 2. Intention to treat cohort.
First or only episode of clinical malaria from IPTp dose 1 until delivery

References

    1. World Health Organization (WHO) Brazzaville, Democratic Republic of Congo: WHO Regional Office for Africa,2004; 2006. A strategic framework for malaria prevention and control during pregnancy in the African region: report AFR/MAL/04/01.
    1. Greenwood BM, Greenwood AM, Snow RW, Byass P, Bennett S, Hatibnjie AB. The Effects of Malaria Chemoprophylaxis Given by Traditional Birth Attendants on the Course and Outcome of Pregnancy. Trans R Soc Trop Med Hyg. 1989;83(5):589–94.
    1. Brabin B. An Assessment of Low-Birth-Weight Risk in Primiparae As An Indicator of Malaria Control in Pregnancy. Int J Epi. 1991;20(1):276–83.
    1. Menendez C, Ordi J, Ismail MR, Ventura PJ, Aponte JJ, Kahigwa E, et al. The impact of placental malaria on gestational age and birth weight. J Infect Dis. 2000;181(5):1740–5.
    1. Granja AC, Machungo F, Gomes A, Bergstrom S, Brabin B. Malaria-related maternal mortality in urban Mozambique. Ann Trop Med Parasitol. 1998;92(3):257–63.
    1. Romagosa C, Ordi J, Saute F, Quinto L, Machungo F, Ismail MR, et al. Seasonal variations in maternal mortality in Maputo, Mozambique: the role of malaria. Trop Med Int Health. 2007;12(1):62–7.
    1. Gamble C, Ekwaru JP, Ter Kuile FO. Insecticide-treated nets for preventing malaria in pregnancy. Cochrane.Database.Syst.Rev. 2006;(2):CD003755.
    1. Njagi JK, Magnussen P, Estambale B, Ouma J, Mugo B. Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial. Trans R Soc Trop Med Hyg. 2003;97(3):277–82.
    1. Mbaye A, Richardson K, Balajo B, Dunyo S, Shulman C, Milligan P, et al. A randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine-pyrimethamine in Gambian multigravidae. Trop Med Int Health. 2006;11(7):992–1002.
    1. 2006 WHO expert consultation on cotrimoxazol propphylaxis in HIV infection.
    1. Ter Kuile FO, Parise ME, Verhoeff FH, Udhayakumar V, Newman RD, van Eijk AM, et al. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-Saharan Africa. Am J Trop Med Hyg. 2004;71(2):41–54.
    1. INDEPTH Network. Ottawa, Canada: International Development Research Centre,2002; 2006. Population and health in developing countries.
    1. Abacassamo F, Enosse S, Aponte JJ, Gomez-Olive FX, Quinto L, Mabunda S, et al. Efficacy of chloroquine, amodiaquine, sulphadoxine- pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria. Trop Med Int Health. 2004;9(2):200–8.
    1. Ter Kuile FO, Terlouw DJ, Phillips-Howard PA, Hawley WA, Friedman JF, Kariuki SK, et al. Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya. Am J Trop Med Hyg. 2003;68(4 Suppl):50–60.
    1. Dubowitz LM, Dubowitz V, Goldberg C. Clinical assessment of gestational age in the newborn infant. J.Pediatr. 1970;77(1):1–10.
    1. Alonso PL, Smith T, Schellenberg JR, Masanja H, Mwankusye S, Urassa H, et al. Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet. 1994;344(8931):1175–81.
    1. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, et al. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet. 2004;364(9443):1411–20.
    1. Ordi J, Ismail MR, Ventura PJ, Kahigwa E, Hirt R, Cardesa A, et al. Massive chronic intervillositis of the placenta associated with malaria infection. Am J Surg Pathol. 1998;22(8):1006–11.
    1. Rogerson SJ, Mkundika P, Kanjala MK. Diagnosis of Plasmodium falciparum malaria at delivery: comparison of blood film preparation methods and of blood films with histology. J Clin Microbiol. 2003;41(4):1370–4.
    1. Ismail MR, Ordi J, Menendez C, Ventura PJ, Aponte JJ, Kahigwa E, et al. Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Hum Pathol. 2000;31(1):85–93.
    1. Macete E, Aide P, Aponte JJ, Sanz S, Mandomando I, Espasa M, Sigauque B, Dobaño C, Mabunda S, Dgedge M, Alonso P, Menendez C. Intermittent preventive treatment for malaria control administered at the time of routine vaccinations in Mozambican infants: a randomized, placebo-controlled trial. J Infect Dis. 2006;194(3):276–285.
    1. Ter Kuile FO, van Eijk AM, Filler SJ. Harare, Zimbabwe: World Health Organisation, Regional Office for Africa; 2005. Can the treatment response in children with symptomatic malaria be used to guide policy for case management and intermittent preventive treatment of malaria in pregnancy? A review of published and unpublished literature.
    1. Parise ME, Ayisi JG, Nahlen BL, Schultz LJ, Roberts JM, Misore A, et al. Efficacy of sulfadoxlne-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg. 1998;59(5):813–22.
    1. Schultz LJ, Steketee RW, Macheso A, Kazembe P, Chitsulo L, Wirima JJ. The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi. Am J Trop Med Hyg. 1994;51(5):515–22.
    1. Shulman CE, Dorman EK, Cutts F, Kawuondo K, Bulmer JN, Peshu N, et al. Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet. 1999;353(9153):632–6.
    1. Filler SJ, Kazembe P, Thigpen M, Macheso A, Parise ME, Newman RD, et al. Randomized Trial of 2-Dose versus Monthly Sulfadoxine-Pyrimethamine Intermittent Preventive Treatment for Malaria in HIV-Positive and HIV-Negative Pregnant Women in Malawi. J Infect Dis. 2006;194(3):286–93.
    1. Challis K, Osman NB, Cotiro M, Nordahl G, Dgedge M, Bergstrom S. Impact of a double dose of sulphadoxine-pyrimethamine to reduce prevalence of pregnancy malaria in southern Mozambique. Trop Med Int Health. 2004;9(10):1066–73.
    1. Menendez C, d'Alessandro U, Ter Kuile FO. Reducing the burden of malaria in pregnancy by preventive strategies. Lancet Infect Dis. 2007;7(2):126–35.

Source: PubMed

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