Table 2 Characteristics of intermittent preventative treatment during pregnancy with sulfadoxine–pyrimethamine (IPTp-SP) related studies conducted in Malawi

1

Verhoeff et al. [17]

March 1993 to June 1994 study period

Compared and evaluated parasite prevalence, anaemia and LBW in mothers who received one, two or three doses of SP during pregnancy, and the incidences of LBW in the infants

575 pregnant women attending antenatal facility at Chikwawa district hospital in Malawi

Interventional, longitudinal study

Assessment was in women who received one, two or three doses of SP during pregnant

No significant difference in parasite prevalence in peripheral or placental blood between women who received one or two SP doses although multigravidea with two dose SP had higher haemoglobin concentrations than those who received one dose (P = 0.009). The mean birthweights were higher, and incidence of LBW lower in babies born to primi- and multi-gravidea who had received two or three doses of SP than those from women who received just one dose (P < 0.03 for each)

SP use was not associated with maternal side-effects or perinatal complications and that multiple doses of SP during pregnancy will lead to a highly significant reduction in the incidence of LBW.

2

Taylor et al. [18]

July 1997 to August 2006 study period

Explored relationships between IPTp-SP, the presence of resistant parasite at delivery, and multiple measures of adverse delivery outcome, including parasite densities, placental histology, maternal haemoglobin concentration and birth weight

177 genotyping and antenatal data of pregnant women delivering at Queens Elizabeth Central Hospital in Blantyre, Malawi

A serial cross section analysis

SP receipt records were obtained from antenatal clinical cards, peripheral and placental blood obtained, and a subset of 25% of available sample from women with positive peripheral blood thick smear were tested for genotyping

Women who received full IPTp with SP (≥2 doses) had lower peripheral (P = 0.018) and placental (P < 0.0001) parasite densities than women who received suboptimal IPTp (<2 doses), mean birthweight in the full IPTp group of 2892 g compared to 2776 g in the suboptimal group (P = 0.086), or LBW prevalence of 11.8% in the full IPTp group compared to 15.8% in the suboptimal group (P = 0.481)

The receipt of SP as IPTp did not raise PAM morbidity despite the increasing prevalence and fixation of SP-resistant P. falciparum haplotypes and therefore SP may be used in modified IPTp regimens as a component of comprehensive antenatal care

3

Rogerson et al. [19]

July 1997 to April 1999 study period

Assessed operational effectiveness of SP by examining the relationship between number of doses of SP prescribed in antenatal clinic and health indicators

1044 women attending the maternity unit at Queen Elizabeth Central Hospital in Blantyre, Malawi

Clinical study

Samples from peripheral and placental blood were collected and tested. With 251 women having received no SP, 555 received 2SP-dose, and 238 received ≥2 SP-doses

SP was associated with a decrease in placental malaria prevalence from 31.9% with no SP to 22.8% with ≥2 SP-doses. Decreased prevalence of LBW from 23% in women not receiving SP to 10.3% in the group receiving ≥2 SP-doses, while maternal and cord blood malaria prevalence and mean cord blood haemoglobin concentrations did not differ with SP usage

IPTp-SP had a positive impact on some indicators while improved implementation and surveillance are critical

4

Filler et al. [14]

October 2002 to March 2005 study period

Determined the efficacy of monthly SP compared to the 2-dose regimen in preventing placental malaria in both HIV positive and negative women. (Results of HIV negative women only are considered in this review)

432 HIV negative women were randomized (216 received 2-dose SP while 216 received monthly SP)

Randomized, non-blinded study

Participants were randomized into either receiving 2-dose SP or monthly SP

In the HIV negative group 2.3% who received monthly SP compared to 6.3% who received 2-dose SP had placental malaria (RR, 0.37)

Monthly IPTp-SP is more efficacious than a 2-dose regimen in preventing placental malaria and that monthly IPTp-SP should be adopted in areas of intense transmission of falciparum malaria

5

Luntamo et al. [21]

December 2003 to October 2006 study period

Examined the potential to prevent preterm deliveries and LBW through intensified gestational intermittent preventive treatment containing antibiotics against malaria and reproductive tract infections

1320 women with uncomplicated second trimester pregnancies at Lungwena Health center, Mangochi, Malawi

A single-center, randomized, partially placebo controlled, outcome assessor-blinded clinical trial

The compared interventions included a standard 2-dose SP as a control group (436), monthly SP (441), and monthly SP combined with two doses of azithromycin (AZI-SP) (443)

Preterm incidence was 17.9% in the controls, 15.4% in the monthly SP group (P = 0.32), and 11.8% in the AZI-SP group (P = 0.01). While comparing with the controls the AZI-SP group had a risk ratio of 0.61 (P = 0.02) and the monthly SP group had a risk ratio of 0.71 (P = 0.09) for LBW

The incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two dose azithromycin

6

Luntamo et al. [22]

December 2003 to October 2007 study period

Assessed the effect of monthly SP and AZI-SP treatments on peripheral malaria parasitemia at delivery in a population of both HIV-positive and –negative women of all gravidities using the PCR-methodology

484 samples from women with uncomplicated second trimester pregnancies at Lungwena Health center, Mangochi, Malawi

A single-center, randomized, partially placebo controlled, outcome assessor-blinded clinical trial

The compared interventions included a standard 2-dose SP as a control group (162), monthly SP (151), and monthly SP combined with two doses of azithromycin (AZI-SP) (171)

Comparing with controls, the monthly group had a risk ratio of 0.33 (P < 0.001) and in the AZI-SP group 0.23 (P < 0.001) for malaria at delivery. While in only HIV-negative women the corresponding figures were 0.26 (P < 0.001) in the monthly SP group ad 0.24 9 (P < 0.001) in the AZI-SP group for malaria at delivery

Increasing the frequency of SP doses during pregnancy improves efficacy against malaria at delivery among HIV-negative women, including a population of both HIV-negative and –positive women of all gravidities

7

Luntamo et al. [23]

December 2003 to October 2006 period of study

Assessed the ability to reduce foetal and neonatal growth faltering through IPTp of malaria and reproductive tract infections with monthly SP, alone or with two doses of azithromycin

1320 women with uncomplicated second trimester pregnancies at Lungwena Health center, Mangochi, Malawi

A randomized, partially placebo controlled, outcome assessor-blinded clinical trial

Participants received either two doses of SP (control) (436), SP monthly (441), or SP monthly and azithromycin (1 g) twice (AZI-SP) (443)

Babies in the AZI-SP group were on average 140 g heavier at birth and 0.6 cm longer at four weeks of age than in the control group

Monthly IPTp-SP regimen provided to all pregnant women is likely to increase mean birthweight and length at four weeks of age in malaria holoendemic areas and adding azithromycin to the regimen seems to increase the benefit in reduction of fetal and neonatal growth faltering

Babies in the monthly SP group were on average 80 g heavier and 0.3 cm longer than in the control group

Compared to controls, the AZI-SP group had a relative risk of 0.61 LBW, 0.60 stunting, and 0.48 underweight at four weeks of age

Compared to controls, the monthly SP group had a relative risk of 0.71 LBW, 1.02 stunting, and 0.87 underweight

8

Gutman et al. [24]

March and August 2010 study period

Assessed the effectiveness of IPTp-SP

703 HIV-negative women were enrolled at Machinga district hospital in Malawi

Cross-sectional delivery survey

Assessment was made in 22% (154) of women who received <2 SP-doses and those that received ≥2 SP-doses

IPTp-SP was associated with a dose-dependent protective effect on composite birth outcomes in primigravidae of an adjusted prevalence ratio of 0.50, 0.30, and 0.18 for 1, 2, and ≥3 doses respectively when compared to 0 doses

IPTp-SP did not reduce the frequency of placental infection but was associated with improved birth outcomes and that IPTp-SP should still continue to be administered although alternative strategies and drugs should be explored