Research Archive

September 2014

Malaria Prevention during Pregnancy - Is There a Next Step Forward?
September 2014

Richard Steketee discusses the two studies by Clara Menéndez and colleagues that describe using mefloquine for the intermittent preventative therapy of malaria in both HIV-positive and HIV-negative pregnant women and outlines the next steps.

 

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial
September 2014

Clara Menéndez and colleagues conducted an open-label randomized controlled trial in HIV-negative pregnant women in Benin, Gabon, Mozambique, and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria. Editors' Summary

 

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
September 2014

Clara Menéndez and colleagues conducted a randomized controlled trial among HIV-positive pregnant women in Kenya, Mozambique, and Tanzania to investigate the safety and efficacy of mefloquine as intermittent preventative therapy for malaria in women receiving cotrimoxazole prophylaxis and long-lasting insecticide treated nets.
Editors' Summary

 

Intermittent preventative treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial

September 2014



Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.

A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.

Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.

 

July 2014

Estimated risk of placental infection and low birthweight attributable to Plasmodium falciparum malaria in Africa in 2010: a modelling study
July 2014

Plasmodium falciparum infection during pregnancy leads to adverse outcomes including low birthweight;
however, contemporary estimates of the potential burden of malaria in pregnancy in Africa (in the absence of
interventions) are poor. We aimed to estimate the need to protect pregnant women from malaria across Africa.

 

Using a mathematical model applied to estimates of the geographical distribution of P falciparum across
Africa in 2010, we estimated the number of pregnant women who would have been exposed to infection that year in the absence of pregnancy-specifi c intervention. We then used estimates of the parity-dependent acquisition of immunity to placental infection and associated risk of low birthweight to estimate the number of women who would have been affected.

 

We estimate that, without pregnancy-specifi c protection, 12∙4 million pregnant women (44∙9% of all
27∙6 million livebirths in malaria endemic areas in Africa in 2010) would have been exposed to infection, with
11∙4 million having placental infection (41∙2% of all livebirths). This infection leads to an estimated 900 000 (95% credible interval [CrI] 530 000–1 240 000) low birthweight deliveries per year. Around the end of the fi rst trimester, when the placenta becomes susceptible to infection, is a key period during which we estimate that 65∙2% (95% CrI 60∙9–70∙0) of placental infections first occur.

 

Our calculations are the only contemporary estimates of the geographical distribution of placental
infection and associated low birthweight. The risk of placental infection across Africa in unprotected women is high. Prevention of malaria before conception or very early in pregnancy is predicted to greatly reduce incidence of low birthweight, especially in primigravidae. The underlying lifetime risk of low birthweight changes slowly with
decreasing transmission, drawing attention to the need to maintain protection as transmission falls.

 

 

January 2014

 

Dihydroartemisinin-Piperaquine Treatment of Multidrug Resistant Falciparum and Vivax Malaria in Pregnancy
January 2014

Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.

 

From April 2004–June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.
Data were available on 6519 pregnant women admitted to hospital; 332 (5.1%) women presented in the first trimester, 324 (5.0%) in the second, 5843 (89.6%) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3%) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26–4.86]); p = 0.006. However in the first trimester 63% (5/8) of women treated with oral DHP miscarried compared to 2.6% (1/38) of those receiving oral quinine; p,0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95%CI 0.97–2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95%CI: 1.17– 8.60]; p = 0.023).

 

In the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.

 

July 2013

Factors Affecting the Delivery, Access, and Use of Interventions to Prevent Malaria in Pregnancy in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

July 2013

 

Malaria in pregnancy has important consequences for mother and baby. Coverage with the World Health Organization recommended prevention strategy for pregnant women in sub-Saharan Africa of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated nets (ITNs) is low. We conducted a systematic review to explore factors affecting delivery, access, and use of IPTp and ITNs among healthcare providers and women.

 

We searched the Malaria in Pregnancy Library and Global Health Database from 1 January 1990 to 23 April 2013, without language restriction. Data extraction was performed by two investigators independently, and data was appraised for quality and content. Data on barriers and facilitators, and the effect of interventions, were explored using content analysis and narrative synthesis. We conducted a meta-analysis of determinants of IPTp and ITN uptake using random effects models, and performed subgroup analysis to evaluate consistency across interventions and study populations, countries, and enrolment sites.

June 2013

A hospital ward using bed netsEffectiveness of Antenatal Clinics to Deliver Intermittent
Preventive Treatment and Insecticide Treated Nets for
the Control of Malaria in Pregnancy in Kenya

June 2013

 

Malaria in pregnancy can have devastating consequences for mother and baby. Coverage with the WHO prevention strategy for sub-Saharan Africa of intermittent-preventive-treatment (IPTp) with two doses of sulphadoxinepyrimethamine (SP) and insecticide-treated-nets (ITNs) in pregnancy is low. We analysed household survey data to evaluate the effectiveness of antenatal clinics (ANC) to deliver IPTp and ITNs to pregnant women in Nyando district, Kenya.

 

We assessed the systems effectiveness of ANC to deliver IPTp and ITNs to pregnant women and the impact on low birthweight (LBW). Logistic regression was used to identify predictors of receipt of IPTp and ITN use during pregnancy. Among 89% of recently pregnant women who attended ANC at least once between 4–9 months gestation, 59% reported receiving one dose of SP and 90% attended ANC again, of whom 57% received a second dose, resulting in a cumulative effectiveness for IPTp of 27%, most of whom used an ITN (96%). Overall ITN use was 89%, and ANC the main source (76%). Women were less likely to receive IPTp if they had low malaria knowledge (0.26, 95% CI 0.08–0.83), had a child who had died (OR 0.36, 95% CI 0.14–0.95), or if they first attended ANC late (OR 0.20, 95% CI 0.06–0.67). Women who experienced side effects to SP (OR 0.18, CI 0.03–0.90) or had low malaria knowledge (OR 0.78, 95% CI 0.11–5.43) were less likely to receive IPTp by directly observed therapy. Ineffective delivery of IPTp reduced its potential impact by 231 LBW cases averted (95% CI 64–359) per 10,000 pregnant women.

 

March 2013

A model of parity-dependent immunity to placental malaria

March 2013

 

Plasmodium falciparum placental infection during pregnancy is harmful for both mother and
child. Protection from placental infection is parity-dependent, that is, acquired over consecutive pregnancies. However, the infection status of the placenta can only be assessed at delivery. Here, to better understand the mechanism underlying this parity-dependence, we
fitted a model linking malaria dynamics within the general population to observed placental
histology. Our results suggest that immunity resulting in less prolonged infection is a greater
determinant of the parity-specific patterns than immunity that prevents placental sequestration.
Our results also suggest the time when maternal blood first flows into the placenta is
a high-risk period. Therefore, preventative strategies implementable before or early in
pregnancy, such as insecticide-treated net usage in women of child-bearing age or any future
vaccine, could substantially reduce the number of women who experience placental infection.

Feburary 2013

Intermittent Preventive Therapy for Malaria During Pregnancy Using 2 vs 3 or More Doses of Sulfadoxine-Pyrimethamine and Risk of Low Birth Weight in Africa, systematic review and metanalysis

February 2013

 

In areas of stable malaria transmission in sub-Saharan Africa, Plasmodium falciparum infection in pregnant women is associated with maternal anemia and low birth weight (LBW) (<2500 g),especially among primigravida and secundigravida and human immunodeficiency virus (HIV)–infected women. The World Health Organization (WHO) recommended intermittent preventive therapy during pregnancy, consisting of at least 2 full treatment doses of sulfadoxine-pyrimethamine for HIV-negative women and at least 3 doses for HIV-positive women not receiving cotrimoxazole, administered presumptively in the second and third trimesters at least 1 month apart. Each dose suppresses or clears any existing asymptomatic infections from the placenta and provides up to 6 weeks of posttreatment prophylaxis. Although the standard 2-dose regimen provides at most 12 weeks of prophylaxis, it has been shown to be effective in reducing LBW and was adopted by 31 of 37 endemic countries in Africa with a policy for intermittent preventive therapy during pregnancy; the remaining countries use a 3-dose or monthly regimen.

October 2012

The Malaria in Pregnancy Library: a biblometric review

October 2012

Malaria is currently endemic in 99 countries worldwide. In 2010, the number of cases globally was estimated at 216 million, representing a 17% decrease compared to estimates in 2000. According to recent models, global malaria mortality peaked in 2004 with 1.8 million deaths, and decreased thereafter to 1.2 million deaths in 2010. This decline is primarily attributed to the increase in funding and expansion of control efforts seen in the last decade. Pregnant women comprise one of two groups particularly vulnerable to malaria, the other being children. Malaria during pregnancy can have devastating consequences to both mother and developing foetus and is associated with mild to severe maternal illness, maternal anaemia, spontaneous miscarriage, stillbirth, preterm delivery and foetal growth retardation.

The Malaria in Pregnancy (MiP) Library is a bibliographic database that was created by the MiP Consortium in 2005 and is updated every four months using a standardized search protocol. A bibliometric review was conducted of the contents of the Library to determine dynamics in the type, content and volume of literature on malaria in pregnancy over time.

September 2012

Maternal anemia at first antenatal visit: prevalence and risk factors in a malaria-endemic area in Benin

September 2012

The risk factors for maternal anemia (hemoglobin level less than 110 g/L) were studied in human immunodeficiency virus–negative pregnant women in Benin at the time of first antenatal visit and prior to any prevention. Data for the first 1,005 pregnant women included in a multicentre randomized controlled trial were analyzed. Anemia was common (68.3%), and malaria and helminth infestations were prevalent in 15.2% and 11.1% of the women. A total of
33.3%, 31.3% and 3.6% of the women were iron, folic acid and vitamin B12 deficient, respectively. These parasitic infections and nutrient deficiencies were associated with a high risk of anemia. Twenty-one percent, 15%, 12%, 11% and 7% of anemia were attributable to malnutrition, malaria, iron, folic acid deficiencies, and helminth infestations, respectively.
Most anemia was caused by factors that could be prevented by available tools, stressing the need to reinforce their implementation and to evaluate their effectiveness throughout the course of the pregnancy.

August 2012

Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda

August 2012

Malaria in pregnancy increases the risk of maternal anaemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium Falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies.

 

Population pharmacokinetic and pharmacodynamic modeling of amodiaquine and desethylamodiaquine in women with Plasmodium vivax malaria during and after pregnancy

August 2012

Amodiaquine is effective for the treatment of P. vivax malaria but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women with P. vivax infection and again after delivery. Twenty-seven pregnant women infected with P. vivax malaria on the Thai-Myanmar border were treated with amodiaquine mono-therapy (10 mg/kg/day) once daily for three days. Nineteen women, with and without P. vivax infections, returned to receive the same amodiaquine dose post-partum. Nonlinear mixed-effect modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of complete in vivo conversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age and absorption lag-time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.

July 2012

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study

July 2012

Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this
also affects the foetal nervous system. The aim of this study was to examine the effects of
malaria on foetal cortex development by three-dimensional ultrasound. Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses. Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies. The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.

 

Pharmacokinetics of Piperaquine in Pregnant Women in Sudan with Uncomplicated Plasmodium falciparum Malaria

July 2012

The pharmacokinetic properties of piperaquine were investigated in 12 pregnant and 12 well-matched, non-pregnant women receiving a three-day oral fixed dose combination regimen of dihydroartemisinin and piperaquine for treatment of uncomplicated Plasmodium falciparum at New Halfa Hospital in eastern Sudan. Frequent venous plasma samples were drawn from the patients over a 63-day period and a complete concentration–time profile was collected for 7 pregnant and 11 non-pregnant patients. Piperaquine was quantified using a liquid chromatography–mass spectrometry/mass spectrometry method. Pregnant women had a significantly higher total drug exposure (median area under the curve [range] = 1,770 [1,200–5,600] hr × ng/mL versus 858 [325–2,370] hr × ng/mL; P = 0.018) and longer time to maximal concentration (4.00 [1.50–4.03] hr versus 1.50 [0.500–8.00] hr; P = 0.02) after the first dose compared with non-pregnant women. There was no other significant difference observed in piperaquine pharmacokinetics between pregnant and non-pregnant women, including no difference in total drug exposure or maximum concentration. The overall pharmacokinetic properties of piperaquine in this study were consistent with previously published reports in non-pregnant patients.

 

June 2012

Determinants of Use of Insecticide Treated Nets for the Prevention of Malaria in Pregnancy: Jinja, Uganda

June 2012

One established means of preventing the adverse consequences of malaria during pregnancy is sleeping under an insecticide treated net (ITN) throughout pregnancy. Despite increased access to this intervention over time, consistent ITN use during pregnancy remains relatively uncommon in sub-Saharan Africa. This study sought to identify determinants of ITN use during pregnancy. Utilizing a populationbased random sample, 500 women living in Jinja, Uganda, who had been pregnant in the past year were interviewed. ITN ownership at the start of pregnancy was reported by 359 women (72%) and 28 women (20%) acquired an ITN after the first trimester of pregnancy. Among 387 ITN owners, 73% reported either always sleeping under the ITN during all trimesters of pregnancy, or after acquiring their net. Owning more than 1 net was slightly associated with always sleeping under an ITN during pregnancy (RR: 1.13; 95% CI: 1.00, 1.28). Women who always slept under an ITN during pregnancy were more likely to be influenced by an advertisement on the radio/poster than being given an ITN free of charge (RR: 1.48; 95% CI: 1.24, 1.76). No differences were found between other socio-demographic factors, pregnancy history, ANC use or socio-cultural factors.

April 2012

Population pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and non-pregnant women with uncomplicated malaria.

April 2012

Pregnant women are particularly vulnerable to malaria. The pharmacokinetic properties of antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and nonpregnant women with uncomplicated malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar border were treated with a standard fixed oral 3-day treatment, and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics were evaluated with nonlinear mixed-effects modeling. The main pharmacokinetic finding was an unaltered total exposure to piperaquine but reduced exposure to dihydroartemisinin in pregnant compared to nonpregnant women with uncomplicated malaria. Piperaquine was best described by a three-compartment disposition model with a 45% higher elimination clearance and a 47% increase in relative bioavailability in pregnant women compared with nonpregnant women. The resulting net effect of pregnancy was an unaltered total exposure to piperaquine but a shorter terminal elimination half-life. Dihydroartemisinin was best described by a one-compartment disposition model with a 38% lower relative bioavailability in pregnant women than nonpregnant women. The resulting net effect of pregnancy was a decreased total exposure to dihydroartemisinin. The shorter terminal elimination half-life of piperaquine and lower exposure to dihydroartemisinin will shorten the posttreatment prophylactic effect and might affect cure rates. The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated malaria needs to be evaluated in larger series.

 

March 2012

Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects

March 2012

The pharmacokinetic properties of many antimalarials are altered during pregnancy. There is often an expanded apparent volume of distribution and increased clearance resulting in lower drug exposure which contributes to higher treatment failure rates. In low transmission settings

treatment responses to antimalarial drug regimens are worse in pregnant women than in age-matched women from the same location who are not pregnant.The artemisinin

derivatives are now central to the treatment of falciparum malaria and artemisinin combination treatments are recommended in the second and third trimesters of pregnancy. Previous studies have suggested that plasma concentrations of the artemisinin derivatives and their common active metabolite dihydroartemisinin (DHA) are low in pregnancy. Finding the correct dose of artesunate (ARS) in pregnancy is necessary not only to obtain optimal cure rates for the individual patient but also to limit the emergence and spread of resistance.

 

Antenatal receipt of sulfadoxine-pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study

March 2012

Antenatal intermittent preventive therapy with 2 doses of sulfadoxine-pyrimethamine (IPTp-SP) is the mainstay of efforts in sub-Saharan Africa to prevent pregnancy-associated malaria (PAM). Recent studies report that drug resistance may cause IPTp-SP to exacerbate PAM morbidity, raising fears that current policies will cause harm as resistance spreads.

We conducted a serial, cross-sectional analysis of the relationships between IPTp-SP receipt, SP-resistant Plasmodium falciparum, and PAM morbidity in delivering women during a period of 9 years at a single site in Malawi. PAM morbidity was assessed by parasite densities, placental histology, and birth outcomes.

The prevalence of parasites with highly SP-resistant haplotypes increased from 17% to 100% (P < .001), and the proportion of women receiving full IPTp (≥2 doses) increased from 25% to 82% (P < .001). Women who received full IPTp with SP had lower peripheral (P = .018) and placental (P < .001) parasite densities than women who received suboptimal IPTp (<2 doses). This effect was not significantly modified by the presence of highly SP-resistant haplotypes. After adjustment for covariates, the receipt of SP in the presence of SP-resistant P. falciparum did not exacerbate any parasitologic, histologic, or clinical measures of PAM morbidity.

 

How Hidden Can Malaria Be in Pregnant Women? Diagnosis by Microscopy, Placental Histology, Polymerase Chain Reaction and Detection of Histidine-Rich Protein 2 in Plasma

March 2012

A major and not sufficiently recognized contributor to the burden of infectious diseases in developing countries is the lack of access to high-quality diagnostic techniques for effective clinical management and monitoring of control interventions. In particular, early diagnosis and treatment of Plasmodium falciparum infection are key to reducing malaria-related morbidity and mortality and are a fundamental aspect in the control and eradication of this disease. Microscopy has been the cornerstone of malaria diagnosis and is recommended where its quality can be maintained. However, rapid diagnostic tests (RDTs) detecting Plasmodium-specific antigens have emerged during recent years as an attractive alternative to microscopy that is able to extend diagnosis to remote and poorly resourced areas. Pregnancy poses specific challenges for the diagnosis of malaria, because P. falciparum parasites may be present in the placenta but absent or undetectable in peripheral blood.

 

 

Adaptive evolution and fixation of drug-resistant Plasmodium falciparum
genotypes in pregnancy-associated malaria: 9-year results
from the QuEERPAM study

March 2012

Sulfadoxine-pyrimethamine (SP) has been widely deployed in Africa for malaria control and molecular evidence of parasite drug-resistance is prevalent. However, the temporal effects on the selection of Plasmodium falciparum are not well understood. A retrospective serial cross-sectional study was conducted between 1997 and 2006 to investigate changes in drug-resistant malaria among pregnant women delivering at a single hospital in Blantyre, Malawi. P. falciparum parasites were genotyped for parasite clone multiplicity and drug-resistance mutations, and the strength of selection upon mutant genotypes was quantified. Results underscore the pressing need for new preventive measures for pregnancy-associated malaria and provide a real-world model of the selection landscape malaria parasites.

 

 

February 2012

Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy

February 2012

The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to
augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.

 

 

December 2011

Costs Associated with Low Birth Weight in a Rural Area
of Southern Mozambique



Low Birth Weight (LBW) is prevalent in low-income countries. Even though the economic evaluation of interventions to reduce this burden is essential to guide health policies, data on costs associated with LBW are scarce. This study aimed to estimate the costs to the health system and to the household and the Disability Adjusted Life Years (DALYs) arising from infant deaths associated with LBW in Southern Mozambique.

 

Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study


The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai–Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments.

Effects of malaria and its treatment in early pregnancy



Malaria can have devastating consequences for pregnant women and their developing fetuses. The lack of information on the effect of malaria in the first trimester has been previously identified as an important knowledge gap in estimating the burden of malaria in pregnancy.

 

November 2011

The pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and non-pregnant women with uncomplicated falciparum malaria


Dihydroartemisinin-piperaquine (DHA PQ) is a fixed dose artemisinin-based combination treatment. Some antimalarials have altered pharmacokinetics in pregnancy. Pregnant women in the 2nd or 3rd trimester and matched non-pregnant women with uncomplicated falciparum malaria were treated with DHA PQ once daily for 3 days. Results analysis suggests that there are no clinically important differences in the pharmacokinetics of DHA or PQ between pregnant and non-pregnant women. However, a more detailed analysis using population pharmacokinetic modelling is needed.

 

August 2011

© 2009 Rajal Thaker, Courtesy of PhotoshareEstimation of gestational age from fundal height: a solution for resource-poor settings


Many women in resource-poor settings lack access to reliable gestational age assessment because they do not know their last menstrual period; there is no ultrasound and methods of newborn gestational age dating are not practised by birth attendants. A bespoke multiple-measures model was developed to predict expected date of delivery determined by ultrasound.

 

July 2011

© 2002 Arturo Sanabria, Courtesy of PhotoshareSuperiority of 3 Over 2 Doses of Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine for the Prevention of Malaria During Pregnancy in Mali

In 2003, Mali introduced intermittent preventive therapy in pregnancy (ITPp) with sulfadoxinepyrimethamine (SP) for the control of malaria in pregnancy, consisting of 2 doses of SP given in the 2nd and 3rd trimester. The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight (LBW).

Pricking fingers for testing
S
ocial and Cultural Factors Affecting Uptake of Interventions for Malaria in Pregnancy in Africa: A Systematic Review


Malaria during pregnancy (MiP) results in adverse birth outcomes and poor maternal health. MiP-related morbidity and mortality is most pronounced in sub-Saharan Africa, where recommended MiP interventions include intermittent preventive treatment, insecticide-treated bednets and appropriate case management.

 

April 2011

© Bita Rodrigues, Courtesy of USAIDIntermittent preventive treatment of malaria in pregnancy: at the crossroads of public health policy


The urgency to identify efficacious drugs and/or new strategies to prevent malaria in pregnancy remains as great as ever. This review summarises the results of recently published SP-IPTp studies from areas of high drug resistance and/or low malaria transmission.

© 2009 Stephanie Suhowatsky, Courtesy of JhpiegoMalaria in pregnancy: small babies, big problem



In this review in Trend in Parasitology, recent discoveries regarding the mechanisms of pathogenesis by which malaria causes fetal growth retardation are discussed in the wider context of placental function and fetal growth.

Pricking fingers for testingEffectiveness of interventions to screen and manage infections during pregnancy on reducing stillbirths


Infection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting important infections during pregnancy, including malaria, on stillbirth or perinatal mortality.


Jan 2011

Protection of pregnant women against malaria still inadequate
A study published in The Lancet Infectious Diseases finds that methods to protect pregnant women from malaria are still underutilised in sub-Saharan Africa.


Sept 2010

Women and malaria research in the 21st Century
Clara Menendez and colleagues in a Plos Medicine Community blog offer reflections on the roles of women in malaria research.