Meta AnalysisID 2318

双氢青蒿素-哌喹对比磺胺多辛-乙胺嘧啶用于妊娠期疟疾预防

CRD42018084651

How does the effect of dihydroartemisinin-piperaquine (DP) compare to sulphadoxine-pyrimethamine (SP) in the prevention of malaria during pregnancy?

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Meta Analysis Id: 2318
Evidence Id: 10876
Core Evidence Id: 10876
Source Meta Analysis Id: 2267
Herb2 Meta Analysis Id: HBMA002267
Crd Id: CRD42018084651
Title: Dihydroartemisinin-piperaquine versus sulphadoxine-pyrimethamine for malaria prevention in pregnancy
Review Question: How does the effect of dihydroartemisinin-piperaquine (DP) compare to sulphadoxine-pyrimethamine (SP) in the prevention of malaria during pregnancy?
Study Type Included: Randomised and quasi-randomised controlled trials will be included. For studies with mixed populations (pregnant and non-pregnant women), only disaggregated data for pregnant women will be included.
Condition Being Studied: Malaria in pregnancy (MIP) refers to the occurrence of a malaria infection in a pregnant woman, and is associated with morbidity and mortality in both the mother and in the newborn. The condition may be asymptomatic with subclinical placental infection, or may present with febrile illness, miscarriages, fetal death and maternal death. The World Health Organisation (WHO) in 2015 reported 212 million cases of malaria and 429,000 deaths, most of which occurred in Africa (WHO 2017). It has also been estimated that about 62% of the 3.6 billion people living in Asia are at risk of malaria infection (Bahtia 2013). The burden of disease is disproportionately heavier in children under 5 years and pregnant women. Recommendations to reduce the burden of malaria include vector control management by indoor residual spraying, effective case management with artemisinin-based combination therapy (ACT) and prevention with long-lasting Insecticide-treated nets (LLIN). In specific risk populations, intermittent preventive treatment is recommended in pregnant women (IPTp), infants (IPTi) and in children 3-59 months living in areas with seasonal transmission i.e. seasonal malaria chemoprevention (SMC) (WHO 2015). In sub-Saharan Africa,an estimated 6.25 million pregnant women have evidence of placental malaria infection at the time of delivery (Desai 2007) and malaria infection can result in up to 900,000 low birth weight deliveries annually in Africa (Walker 2014). Other known consequences of MIP include maternal anaemia, maternal mortality and placental malaria (Kakuru 2016). Though malaria infection has been reported in the first trimester of pregnancy, IPTp with sulphadoxine-pyrimethamine (SP) is recommended to be commenced as early as possible in the second trimester at each scheduled antenatal visit, provided that the doses are at least one month apart, with the objective of ensuring that at least three doses are received (WHO 2015). Although IPTp with sulphadoxine-pyrimethamine (SP) has been reported to be a safe and cost-effective drug for prophylaxis of MIP, reducing malaria infections and improving maternal and neonatal outcomes (Schultz 1994; Shulman 1999; WHO 2004; Wilson 2011), parasite resistance to SP is widespread and continues to increase, and this may erode the gains obtained from the effect of the intervention. Currently ACT has been recommended for the treatment of malaria across all ages, including the second and third trimesters of pregnancy (WHO 2015). Its potential use as a chemoprophylactic agent in the prevention of MIP is therefore important.
Participant: Pregnant women who are living in malaria-endemic areas. Inclusion: women in the second and third trimesters of pregnancy. Exclusion: women in the first trimester of pregnancy
Animal
Human Disease Modelled
Intervention: Description of the intervention: Dihydroartemisinin-piperaquine (DP) is a fixed-dose artemisinin-based combination therapy (ACT) consisting of an artemisinin active metabolite and piperaquine, which is a Bis-4-aminoquinoline. Trials conducted on DP as chemoprophylaxis in non-pregnant populations show that it is effective and well tolerated (Chen 1982). The action of DP is due to a combination of the characteristics of its components which act synergistically. Dihydroartemisinin is a fast-acting compound with a short half-life, while piperaquine acts slowly, is less rapidly absorbed, and has a longer biological half-life. This results in a compound with a rapid parasite clearance and a relatively long period of protection against re-infection. Dihydroartemisinin causes free-radical damage to the parasite membrane systems, interfering with mitochondrial functions (EMC 2017). The exact mechanism of action of piperaquine is unknown, but it is thought to be similar to that of chloroquine, another 4-aminoquinoline which is known to prevent hemoglobin degradation from occurring in the food vacuoles of intraerythrocytic trophozoites by accumulating in them, and inhibiting the heme polymerase enzyme (Slater 1993). DP has been reported to be effective, like other ACTs, in achieving high cure rates with low side effects in the treatment of malaria infection (WHO 2015). As one of the five WHO-recommended ACTs for the treatment of uncomplicated P. falciparum malaria, the safety, efficacy and effectiveness of DP have been assessed in various trial settings with a reported PCR-adjusted treatment failure rate of 5% or lower in both adults and children (WHO 2015). DP has comparable efficacy and safety profile to Artemether - Lumefantrine (AL) in the treatment of uncomplicated malaria in African children from varying endemic settings (Burkina Faso, Kenya, Mozambique, Uganda and Zambia).There was a lower occurrence of new infections within the 42-day follow up period in the Dihydroartemisinin-piperaquine group, indicative of a longer post-treatment prophylactic effect (Bassat 2009). Recent reports from some clinical trials in malaria endemic regions have shown the potentials of DP as an IPTp agent, given in the second and third trimesters of pregnancy, as there was an increased effectiveness of DP in the cure and reduction in incidence of malaria infection in pregnancy compared to SP (Kakuru 2016). DP reduced the risk of malaria infections when compared to SP, with no significant difference in neonatal outcomes or in the risk of serious adverse events (Desai 2015a; Kakuru 2016). Monthly prophylactic dosage of DP as IPTp has been reported to be feasible (Kakuru 2016, Rijken 2011). Reported side effects of DP include anorexia, nausea, vomiting, diarrhea, headache and dizziness (Denis 2002). QTc prolongation has also been reported with DP use (EMA 2011), though this effect is not influenced by pregnancy (Benjamin 2015). Trials conducted on amodiaquine and mefloquine as alternatives to SP for chemoprophylaxis in the second and third trimesters of pregnancy indicated that they are poorly tolerated as IPTp agents, without convincing evidence of superior benefit when compared with SP (Clerk 2008; Gonzalez 2014). SP and mefloquine resistance have been widely reported in South East Asia, particularly the Thai-Cambodia border within the Greater Mekong subregion (Song 2011). How the intervention might work: The half-life of DP of 19-28 days, is longer than that of SP of 4-11 days (Gutman 2017). Being a long-acting ACT, DP can provide several additional weeks of post-treatment prophylaxis compared to shorter-acting drugs, which would be of importance in areas of highly seasonal transmission (Cairns 2015).The artemisinin-based compounds also reduce the development of gametocytes and their transport in peripheral blood, thereby decreasing the ability of the parasite to infect mosquitoes for further transmission (Price 1996). An important public health benefit of this effect is a potential reduction in the post-treatment transmission of malaria, particularly in areas of low or seasonal transmission (Zani 2014). These features make DP a suitable candidate for prophylaxis against malaria infections, as it could potentially provide protection against re-infection for a longer period (Okell 2014). This characteristic of DP could be beneficial from both clinical and policy implementation perspectives; if there is a missed dose of the monthly IPTp, the longer half-life of DP may confer more protection from malaria compared to SP. Repeated doses of the drug are also feasible, as fewer serious adverse events were reported in comparison with SP when a monthly IPTp regimen with DP was used (Gutman 2017). Although limited by small sample sizes, DP was reported in Thailand and Indonesia to be effective in the treatment of repeated recrudescent malaria infections among pregnant women (Poespoprodjo 2008; Rijken 2008). There is a cohort of pregnant women who are excluded from receiving IPTp-SP, as they are not given the routine SP chemoprophylaxis because of a history of hypersensitivity to sulphonamides. This group of pregnant women could potentially benefit from IPTp with DP, as it does not contain sulphonamides, and does not require daily dosing like proguanil which is the alternative chemoprophylaxis agent usually offered in such cases. Expanding access to IPTp through DP to this group of women could further reduce the burden of malaria-related feto-maternal morbidity and mortality in endemic areas.
Comparator Control: The World Health Organisation (WHO) recommends the use of sulphadoxine-pyrimethamnie (SP) for IPTp, but the growing resistance to SP (Baraka 2015, Braun 2015, Gutman 2015, Iriemenam 2012) has led to a number of studies assessing combination therapies as potential alternatives to SP for IPTp (Benjamin 2015; Desai 2015a, Gonzalez 2014, Kakuru 2016). Systematic reviews on IPTp with SP show that the reduction in risk for low birth weight is consistent across a wide range of parasite resistance to SP (Kayentao 2013, Desai 2015b). IPTp-SP remains effective in preventing adverse maternal and fetal outcomes even in areas where > 90% of P. falciparum parasites carry quintuple mutations (triple pfdhfr and double pfdhps), which are associated with therapeutic failure of SP treatment (WHO 2015). However, the extent of compromise to the efficacy of IPT-SP in areas where parasites carrying pfdhfr/pfdhps sextuple mutations have been reported is a cause for concern (Braun 2015, Gutman 2015). The prevalence of P. falciparum pfdhr double and triple mutations among pregnant women five years after the commencement of IPTp-SP in Burkina Faso was reported as 35.7% and 11.4% respectively (Tahita 2015). SP resistance levels greater than 90% for pfdhfr/pfdhps quintuple or sextuple mutations have been reported in Uganda (Braun 2015), and Pfdhfr triple mutation prevalence of 70.6% to 93.3% has been reported in Tanzania (Baraka 2015). SP resistance has been documented to increase as its use increases, despite the recent report of the safety of SP when used up to five times in pregnancy (Iriemenam 2012; WHO 2012).
Main Outcome: 1) Clinical malaria episodes during pregnancy (presence of asexual parasites in peripheral blood and fever or a history of fever). 2) Placental malaria infection (as defined by the authors).
Outcome Measure
Additional Outcome: Effectiveness: 1) Mean haemoglobin and maternal anaemia (hemoglobin level <11g/dl as defined by WHO). 2) Maternal malaria infection assessed one month post IPT, and at delivery (asymptomatic presence of asexual parasites in peripheral blood). 3) Low birth weight prevalence (<2500g). Safety: 4) All-cause and malaria-specific mortality, hospitalization and other adverse events.
Study Method: Intervention, Prevention, Systematic review
Keyword: Artemisinins; Drug Therapy; Drug Therapy, Combination; Female; Humans; Infant; Infant Health; Malaria; Maternal Health; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy Outcome; Primary Prevention; Pyrimethamine; Quinolines; Sulfadoxine; Treatment Outcome
Contact: Atinuke Olaleye [email protected]
Organisational Affiliation
Funding Source
Other Selection Criteria
Final Publication
Same Topic Review
Published Protocol
Review Type
Language
Country: Nigeria
Review Stage: Review Ongoing
First Submission Date: 2018-01-05
Registration Date: 2018-01-17
Anticipated Start Date: 2018-01-08
Anticipated Completion Date: 2018-03-10
Title Cn: 双氢青蒿素-哌喹对比磺胺多辛-乙胺嘧啶用于妊娠期疟疾预防
Title En: Dihydroartemisinin-piperaquine versus sulphadoxine-pyrimethamine for malaria prevention in pregnancy
Bilingual Status: complete