An evaluation of the effects of intermittent sulfadoxine—pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi

Verhoeff, Francine H.; Brabin, Bernard; Chimsuku, L.; Kazembe, Peter N.; Russell, William Howard; Broadhead, Robin L.

doi:10.1080/00034983.1998.11813273

Cited by 104 publications

(110 citation statements)

References 14 publications

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“…46 This has been effective in reducing the incidence of LBW infants, especially those born to primigravidae, and in reducing maternal anaemia. [47][48][49] Trials of sulphadoxinepyrimethamine have reduced placental malaria and may explain how chemos s prophylaxis increases birth weight 38,50 Malaria prophylaxis has had little effect on the rate of other birth outcomes such as stillbirths or neonatal deaths. 48 In our study, chloroquine was the recoms s mended chemoprophylactic but had limited effectiveness in preventing infecs s tion because chloroquine resistance is common.…”

Section: Discussionmentioning

confidence: 99%

Adverse birth outcomes in United Republic of Tanzania - impact and prevention of maternal risk factors

Watson-Jones

Weiss

Changalucha

et al. 2007

Bull World Health Organ

130

121

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Objective To determine risk factors for poor birth outcome and their population attributable fractions. Methods 1688 women who attended for antenatal care were recruited into a prospective study of the effectiveness of syphilis screening and treatment. All women were screened and treated for syphilis and other reproductive tract infections (RTIs) during pregnancy and followed to delivery to measure the incidence of stillbirth, intrauterine growth retardation (IUGR), low birth weight (LBW) and preterm live birth. Findings At delivery, 2.7% of 1536 women experienced a stillbirth, 12% of live births were preterm and 8% were LBW. Stillbirth was independently associated with a past history of stillbirth, short maternal stature and anaemia. LBW was associated with short maternal stature, ethnicity, occupation, gravidity and maternal malaria whereas preterm birth was associated with occupation, age of sexual debut, untreated bacterial vaginosis and maternal malaria. IUGR was associated with gravidity, maternal malaria, short stature, and delivering a female infant. In the women who had been screened and treated for syphilis, in between 20 and 34% of women with each outcome was estimated to be attributable to malaria, and 63% of stillbirths were estimated as being attributable to maternal anaemia. Screening and treatment of RTIs was effective and no association was seen between treated RTIs and adverse pregnancy outcomes. Conclusion Maternal malaria and anaemia continue to be significant causes of adverse pregnancy outcome in sub-Saharan Africa. Providing reproductive health services that include treatment of RTIs and prevention of malaria and maternal anaemia to reduce adverse birth outcomes remains a priority. Voir page 16 le résumé en français. En la página 16 figura un resumen en español.

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Section: Discussionmentioning

confidence: 99%

Adverse birth outcomes in United Republic of Tanzania - impact and prevention of maternal risk factors

Watson-Jones

Weiss

Changalucha

et al. 2007

Bull World Health Organ

130

121

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“…The World Health Organization recommends that women living in sub-Saharan Africa receive at least two doses of intermittent preventive treatment (IPTp) with sulfadoxinepyrimethamine (SP) to prevent malaria and improve pregnancy outcomes (1)(2)(3)(4)(5) and this advice is widely followed. However, the rapid spread of SP-resistant parasites might undermine the efficacy of SP-IPTp, although it still confers benefits in areas with low to moderate levels of drug resistance (6).…”

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confidence: 99%

Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment

Harrington

Mutabingwa

Muehlenbachs

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

188

244

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Intermittent preventive treatment in pregnancy (IPTp) is used to prevent Plasmodium falciparum malaria. However, parasites resistant to the IPTp drug sulfadoxine-pyrimethamine (SP) have emerged worldwide, and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice. In a prospective delivery cohort in Muheza, Tanzania, we examined the effects of SP IPTp on parasite resistance alleles, parasite diversity, level of parasitemia, and inflammation in the placenta. IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581, an increase in the level of parasitemia, and more intense placental inflammation. The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use. These findings support a model of parasite release and facilitation, whereby the most highly resistant parasites out-compete less fit parasite populations and overgrow under drug pressure. Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance.evolution of drug resistance ͉ intermittent preventive treatment in pregnancy ͉ malaria drug resistance ͉ pregnancy malaria M alaria during pregnancy causes both maternal and fetal morbidity and mortality, including the deaths of an estimated 100,000 infants each year because of malaria-related low birth weight. The World Health Organization recommends that women living in sub-Saharan Africa receive at least two doses of intermittent preventive treatment (IPTp) with sulfadoxinepyrimethamine (SP) to prevent malaria and improve pregnancy outcomes (1-5) and this advice is widely followed. However, the rapid spread of SP-resistant parasites might undermine the efficacy of SP-IPTp, although it still confers benefits in areas with low to moderate levels of drug resistance (6). The effect of SP IPTp in areas where resistant parasites are more widespread has not been studied.Pyrimethamine and sulfadoxine target the parasite proteins DHFR and DHPS, respectively, and increasing resistance is conferred by ordered accumulating point mutations, of which DHPS codon 581 is one of the final to occur (7). The mutation at DHPS codon 581 has been associated with high-level in vitro resistance (8), as well as treatment failure in children (9, 10). Single-dose treatment of children with SP has been associated with an increase in parasite resistance alleles (11, 12), but little work has been done to examine the relationship between IPTp and selection for drug resistance alleles. One recent study observed an increased prevalence of placental infections harboring the DHFR triple mutant in women who had received pyrimethamine prophylaxis during pregnancy, as compared with women who had not (13). In contrast, IPTp use was not related to increased prevalence of resistance alleles at the same study site (14). Modeling studies have proposed that IPTp is less likely to contribute to accumulating drug resistance as...

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“…Although the HIV testing regimen is more complicated, since it requires adequate laboratory facilities and trained counseling staff, we thought it was important to consider this option because of noted differences in the efficacy of SP in reducing placental malaria in HIV-positive women compared with HIV-negative women. 14,15 The two-dose SP, monthly SP, and HIV-testing regimens all decreased placental parasitemia rates in primigravidae and secundigravidae and were estimated to avert more cases of LBW than the febrile case management approach. Although ANC costs for SP were higher for the two-dose and monthly-dose presumptive treatment regimens, the estimated incidence of LBW cases was lower and, therefore, medical care costs were lower, producing lower overall health care costs.…”

Section: Resultsmentioning

confidence: 99%

“…[13][14][15] However, one must also consider the ability to deliver various prevention regimens. The two-dose SP regimen can conveniently be combined with the administration of the two doses of tetanus toxoid that are provided to primigravidae in many countries.…”

Section: Resultsmentioning

confidence: 99%

“…13,14 In addition, in Malawi, women who received two or more doses of SP were less likely to deliver LBW infants compared with women who received only one dose of SP. 15 A recent study in Kenya 14 has examined the efficacy of SP in decreasing placental parasitemia and LBW in human immunodeficiency virus (HIV)-positive women compared with HIV-negative ones. This investigation showed that while two intermittent SP treatment doses are sufficient to decrease placental parasitemia rates in HIV-negative women, HIV-positive women required a monthly treatment regimen (achieving at least three doses of SP) to attain similar outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria-associated low birth weight.

Wolfe

Parise²,

Haddix³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Prevention of placental malaria through administration of antimalarial medications to pregnant women in disease-endemic areas decreases the risk of delivery of low birth weight (LBW) infants. In areas of high Plasmodium falciparum transmission, two intermittent presumptive treatment doses of sulfadoxine-pyrimethamine (SP) during the second and third trimesters of pregnancy are effective in decreasing the prevalence of placental malaria in human immunodeficiency virus (HIV)-negative women, while HIV-positive women may require a monthly SP regimen to reduce their prevalence of placental parasitemia. A decision-analysis model was used to compare the costeffectiveness of three different presumptive SP treatment regimens with febrile case management with SP in terms of incremental cost per case LBW prevented. Factors considered included HIV seroprevalence, placental malaria prevalence, LBW incidence, the cost of SP, medical care for LBW infants, and HIV testing. For a hypothetical cohort of 10,000 pregnant women, the monthly SP regimen would always be the most effective strategy for reducing LBW associated with malaria. The two-dose SP and monthly SP regimens would prevent 172 and 229 cases of LBW, respectively, compared with the case management approach. At HIV seroprevalence rates greater than 10%, the monthly SP regimen is the least expensive strategy. At HIV seroprevalence rates less than 10%, the two-dose SP regimen would be the less expensive option. When only antenatal clinic costs are considered, the two-dose and monthly SP strategies cost US$11 and $14, respectively, well within the range considered cost effective. Presumptive treatment regimens to prevent LBW associated with malaria and the subsequent increased risk of mortality during the first year of life are effective and cost effective strategies in areas with both elevated HIV prevalence and malaria transmission rates.

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An evaluation of the effects of intermittent sulfadoxine—pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi

Cited by 104 publications

References 14 publications

Adverse birth outcomes in United Republic of Tanzania - impact and prevention of maternal risk factors

Adverse birth outcomes in United Republic of Tanzania - impact and prevention of maternal risk factors

Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment

Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria-associated low birth weight.

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