Intermittent Preventive Therapy In Pregnancy Research Articles

Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016\u20132017

BackgroundResistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where further investigations are needed.MethodsDried blood spots were collected from 398 patients (age range 5–59 years, 99% male) with Plasmodium falciparum infections detected using rapid diagnostic tests over two rounds of sample collection conducted in 2016 and 2017 in Komé, South-West Chad. Specimens were genotyped using amplicon sequencing or qPCR for validated markers of anti-malarial resistance including partner drugs used in artemisinin-based combination therapy (ACT).ResultsNo mutations in the pfk13 gene known to be associated with artemisinin resistance were found but a high proportion of parasites carried other mutations, specifically K189T (190/349, 54.4%, 95%CI 49.0–59.8%). Of 331 specimens successfully genotyped for pfmdr1 and pfcrt, 52% (95%CI 46.4–57.5%) carried the NFD-K haplotype, known to be associated with reduced susceptibility to lumefantrine. Only 20 of 336 (6.0%, 95%CI 3.7–9.0%) had parasites with the pfmdr1-N86Y polymorphism associated with increased treatment failures with amodiaquine. Nearly all parasites carried at least one mutation in pfdhfr and/or pfdhps genes but ‘sextuple’ mutations in pfdhfr—pfdhps including pfdhps -A581G were rare (8/336 overall, 2.4%, 95%CI 1.2–4.6%). Only one specimen containing parasites with pfmdr1 gene amplification was detected.ConclusionsThese results provide information on the likely high efficacy of artemisinin-based combinations commonly used in Chad, but suggest decreasing levels of sensitivity to lumefantrine and high levels of resistance to sulfadoxine-pyrimethamine used for seasonal malaria chemoprevention and intermittent preventive therapy in pregnancy. A majority of parasites had mutations in the pfk13 gene, none of which are known to be associated with artemisinin resistance. A therapeutic efficacy study needs to be conducted to confirm the efficacy of artemether-lumefantrine.

Intermittent screening and treatment with artemisinin-combination therapy versus intermittent preventive treatment with sulphadoxine-pyrimethamine for malaria in pregnancy: a systematic review and individual participant data meta-analysis of randomised clinical trials.

BackgroundIn sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections.MethodsWe searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental Plasmodium falciparum at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789.FindingsFive trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where dhfr/dhps quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I2=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I2=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I2=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I2=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57).InterpretationISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections.FundingCenters for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.

Towards Intermittent Preventive Therapy in Pregnancy with Dihydroartemisinin-Piperaquine?

Malaria is a major cause of adverse pregnancy outcomes in sub-Saharan Africa, but resistance to sulfadoxine-pyrimethamine, the only antimalarial recommended by the World Health Organisation for intermittent preventive therapy, is threatening the gains made in the last two decades. In this issue, Mlugu and colleagues present the results of a trial of dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine. The results are impressive but raise the question why they differ so much from three previous trials.

Uptake challenges of intermittent preventive malaria therapy among pregnant women and their health care providers in the Upper West Region of Ghana: A mixed-methods study

BackgroundMalaria in pregnancy remains a major public health problem in endemic countries, especially in sub-Saharan Africa (SSA). Existing interventions such as intermittent preventive therapy in pregnancy (IPTp) using sulfadoxine-pyrimethamine (SP) are effective against placental malaria. However, low uptake of this intervention is a challenge in SSA. This study assessed factors affecting IPTp-SP uptake among pregnant women as well as their health care providers, including health system-related factors. MethodsFrom November 2018 until May 2019 a mixed-methods study was conducted in one urban and one rural district of the Upper West Region of Ghana. A multi-stage sampling technique was used to recruit 740 3rd trimester pregnant women and 74 health service providers from 37 antenatal care (ANC) facilities. Quantitative data was collected through a standard questionnaire from pregnant women and ANC service providers. Three focus group discussions (FGDs) were conducted in each district with pregnant women who had defaulted on their IPTp doses to collect information about the challenges in accessing IPTp-SP. The primary outcome was the uptake of IPTp-SP during antenatal care visits. In addition, the health care provider and health system-related factors on the administration of SP were assessed, as well as details of folic acid (FA) supplementation. Data were analysed using descriptive statistics and Poisson regression. ResultsResponses from 697 pregnant women were analysed. Of these, 184 (26.4%) had taken the third dose of SP (SP3) in line with international guidelines. IPTp-SP uptake was low and significantly associated with the number of maternal ANC contacts and their gestational age at 1st ANC contact. Most pregnant women were regularly co-administered SP together with 5 mg of FA, in contrast to the international recommendations of 0.4 mg FA. The main challenges to IPTp-SP uptake were missed ANC contacts, knowledge deficiencies among pregnant women of the importance of IPTp, and frequent drug stock outs, which was confirmed both from the ANC providers as well as from the pregnant women. Further challenges reported were provider negligence/absenteeism, adverse drug reactions, and mobile residency of pregnant women. ConclusionsThe uptake of IPTp-SP in the study area is still very low, which is partly explained by frequent drug stock outs at health facilities, staff absenteeism, knowledge deficiencies among pregnant women, and missed ANC contacts. The high dosing of co-administered FA is against international recommendations. These observations need to be addressed by the national public health authorities.

Piperaquine Pharmacokinetics during Intermittent Preventive Treatment for Malaria in Pregnancy.

Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4- to 8-week intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, at the time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modeling with a prior approach. In total, data from 366 Kenyan and 101 Indonesian women were analyzed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n = 5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45% (95% confidence interval [CI], 1.8 to 26.5%) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/ml). Translational simulations suggest that providing the full treatment course of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of DP has the potential to offer optimal prevention of malaria during pregnancy. (This study has been registered at ClinicalTrials.gov under identifier NCT01669941 and in the ISRCTN under number ISRCTN34010937.).

Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi.

Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients. We measured SP-resistance allele frequencies in Malawian women participating in a trial comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped polymerase chain reaction-detected parasites using deep sequencing of SP-resistance alleles. Among 125 placental infections, A581G-bearing parasites were associated with reduced birth weight (mean difference [MD], 252 g; 95% confidence interval [CI], 46-457; P = .017). Relative to ISTp, IPTp-SP was associated with higher birth weights in women with wild-type parasites (MD, 116 g; 95% CI, -40 to 272; P = .142) and lower birth weights in women with A581G-bearing parasites (MD, 192 g; 95% CI, -264 to 648; P = .385) (Pinteraction = .033). Similar associations were noted on gestational age (Pinteraction = .075). Amongst only IPTp-SP recipients, relative to women who last received SP > 4 weeks before delivery, recent SP receipt was associated with lower birth weight in women with wild-type parasites (MD, 118 g; 95% CI, -376 to 139; P = .361) and higher birth weight in women with A581G-bearing parasites (MD, 783 g; 95% CI, -20 to 1586; P = .054) (Pinteraction = .005). The effectiveness in birth weight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP. www.isrctn.com/ISRCTN69800930.

The efficacy of intermittent preventive therapy in the eradication of peripheral and placental parasitemia in a malaria-endemic environment, as seen in a tertiary hospital in Abuja, Nigeria.

To determine whether intermittent preventive therapy in pregnancy (IPTp) eradicates peripheral and placental malaria and improves birth weight. A cross-sectional study was conducted of 426 pregnant mothers on IPTp with sulphadoxine-pyrimethamine against malaria who presented in labor, at National Hospital Abuja, Nigeria between January and June 2017. The hospital is within the malaria-endemic zone of West Africa. Consenting pregnant women with uncomplicated singleton term pregnancy who had antenatal care in the hospital and lived in the study area for at least 6months were consecutively recruited. Peripheral and placental blood were collected and examined for malaria parasite by microscopy. Babies were weighed at birth. The prevalence of peripheral malaria parasitemia and placental parasitization were 12.9% (95% confidence interval [CI] 10.0-16.6) and 9.4% (95% CI 7.0-12.7), respectively. Parasite density in both peripheral parasitemia and placental parasitization was low among the women that took IPTp, decreasing with increasing doses, with no parasitemia or parasitization in women that took up to three doses. Birth weight was lower in babies of mothers with plasmodium infestation than in those without infestation (P<0.001, P=0.024). IPTp reduces both peripheral parasitemia and placental parasitization, with the capacity to eliminate or prevent them. IPTp also reduces low birth weight.

Adverse birth outcomes among mothers who received intermittent preventive treatment with Sulphadoxine-Pyrimethamine in the low malaria transmission region

BackgroundMalaria in pregnancy increases the risk of adverse birth outcomes such as low birth weight (LBW), maternal and foetal anemia. In Tanzania, some areas have attained low malaria transmission. However, data on the burden of preterm delivery, LBW, maternal and foetal anemia following substantial reduction of malaria transmission in recent years is still scarce in these settings.MethodsA study involving 631 pregnant women was conducted at Mwananyamala referral hospital in Dar es Salaam from April to August, 2018. Study enrollment was done prior to delivery. Structured interview and antenatal clinic cards were used to obtain data including the use of intermittent preventive therapy in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP). Infants birth weights were recorded, maternal venous and cord blood were taken for testing of malaria and determination of haemoglobin (Hb) levels. Chi-square test and regression analysis were done to identify risk factors for preterm delivery, LBW, maternal and foetal anemia.ResultsThe prevalence of malaria among mothers who used at least one dose of IPTp-SP was 0.6% (4/631). Fourteen mothers (2.2%) did not use IPTp-SP and had no malaria infection. The prevalence of maternal anemia, LBW, foetal anemia and preterm delivery was 40.6, 6.5, 5.9 and 9.2% respectively. Participants who were malaria positive had 11 times more risk of LBW compared to those who were negative (AOR, 11; 95%, CI 1.07–132.2; p = 0.04). The risk of delivering babies with LBW was 1.12 times high among mothers who were ≤ 36 weeks of gestation (AOR, 1.12; 95% CI, 0.06–0.25; p = < 0.001). The use of ≥3 doses of IPTp-SP was associated with 83% decrease in risk of LBW compared to those who did not use any dose of IPTp-SP (AOR, 0.17; 95% CI, 0.03–0.88; p = 0.05). Severe anaemia at delivery was associated with seven times increased risk of preterm delivery compared to non-anemic participants (AOR, 6.5; 95% CI, 1.49–28.16; p = 0.013).ConclusionDespite the reduced malaria transmission and use of IPTp-SP, prevalence of preterm delivery, maternal anemia, LBW and foetal anemia is still high in Tanzania. The recommended ≥3 doses of IPTp-SP should continue be provided even in areas with substantial reduction of malaria.

Use of Intermittent Preventive Treatment among Pregnant Women in Sub-Saharan Africa: Evidence from Malaria Indicator Surveys.

Uptake of intermittent preventive therapy in pregnancy (IPTp) with sulfadoxine-pyrimethamine (IPTp-SP) is a clinically-proven method to prevent the adverse outcomes of malaria in pregnancy (MiP) for the mother, her foetus, and the neonates. The majority of countries in sub-Saharan Africa have introduced IPTp policies for pregnant women during the past decade. Nonetheless, progress towards improving IPTp coverage remains dismal, with widespread regional and socioeconomic disparities in the utilisation of this highly cost-effective service. In the present study, our main objective was to measure the prevalence of IPTp uptake in selected malaria-endemic countries in sub-Saharan Africa, and to investigate the patterns of IPTp uptake among different educational and wealth categories adjusted for relevant sociodemographic factors. For this study, cross-sectional data on 18,603 women aged between 15 and 49 years were collected from the Malaria Indicator Surveys (MIS) conducted in Burkina Faso, Ghana, Mali, Malawi, Kenya, Nigeria, Sierra Leone, and Uganda. The outcome variable was taking three doses of IPTp-SP in the last pregnancy, defined as adequate by the WHO. According to the analysis, the overall prevalence of taking three doses of IPTp-SP in the latest pregnancy was 29.5% (95% CI = 28.2–30.5), with the prevalence being highest for Ghana (60%, 95% CI = 57.1–62.8), followed by Kenya (37%, 95% CI = 35.3–39.2) and Sierra Leone (31%, 95% CI = 29.2–33.4). Women from non-poor households (richer—20.7%, middle—21.2%, richest—18.1%) had a slightly higher proportion of taking three doses of IPTp-SP compared with those from poorest (19.0%) and poorer (21.1%) households. Regression analysis revealed an inverse association between uptake of IPTp-SP and educational level. With regard to wealth status, compared with women living in the richest households, those in the poorest, poorer, middle, and richer households had significantly higher odds of not taking at least three doses of IPTp-SP during their last pregnancy. The present study concludes that the prevalence of IPTp-SP is still alarmingly low and is significantly associated with individual education and household wealth gradient. Apart from the key finding of socioeconomic disparities within countries, were the between-country variations that should be regarded as a marker of inadequate policy and healthcare system performance in the respective countries. More in-depth and longitudinal studies are required to understand the barriers to, and preferences of, using IPTp-SP among women from different socioeconomic backgrounds.

Intermittent Preventive Therapy in Pregnancy and Incidence of Low Birth Weight in Malaria-Endemic Countries.

To estimate the impact of hypothetical antimalarial and nutritional interventions (which reduce the prevalence of low midupper arm circumference [MUAC]) on the incidence of low birth weight (LBW). We analyzed data from 14 633 pregnancies from 13 studies conducted across Africa and the Western Pacific from 1996 to 2015. We calculated population intervention effects for increasing intermittent preventive therapy in pregnancy (IPTp), full coverage with bed nets, reduction in malaria infection at delivery, and reductions in the prevalence of low MUAC. We estimated that, compared with observed IPTp use, administering 3 or more doses of IPTp to all women would decrease the incidence of LBW from 9.9% to 6.9% (risk difference = 3.0%; 95% confidence interval = 1.7%, 4.0%). The intervention effects for eliminating malaria at delivery, increasing bed net ownership, and decreasing low MUAC prevalence were all modest. Increasing IPTp uptake to at least 3 doses could decrease the incidence of LBW in malaria-endemic countries. The impact of IPTp on LBW was greater than the effect of prevention of malaria, consistent with a nonmalarial effect of IPTp, measurement error, or selection bias.

Intermittent preventive therapy in pregnancy and incidence of low birth weight in malaria-endemic countries

Intermittent preventive therapy in pregnancy and incidence of low birth weight in malaria-endemic countries

Intermittent preventive therapy in pregnancy with sulfadoxine/pyrimethamine for malaria prophylaxis among parturients in Ilorin, Nigeria

Background: The use of intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine (IPTp-SP) for malaria remains an important tool for improving pregnancy outcome in malaria endemic areas. Objective: To assess the knowledge, attitude, and factors associated with the use of IPTp-SP among antenatal clinic attendees in Ilorin. Materials and Methods: A prospective, multicentre, cross-sectional study among consenting parturients receiving antenatal care at three public health facilities in Ilorin, Nigeria. Statistical analysis was conducted with the Statistical Package for the Social Sciences version 20.0 software (SPSS Inc., Chicago, IL, United States) with the calculation of percentages, chi square, odds ratios (ORs), and confidence intervals (CIs); P Results: There were 422 participants with mean age of 28.8 ± 4.7 years and 368 (87.2%) were aware of the use of IPTp-SP for malaria prevention, while 388 (91.9%) were willing to use IPTp-SP. Only 154 (36.5%) had prescription for IPTp-SP among whom 139 (90.3%) were compliant; IPTp-SP uptake in preceding pregnancy was 148 (59.7%). The most common reason for the nonuse of IPTp-SP prescribed was the fear of harm to the fetus (53.3%). Significant determinants of willingness to use IPTp-SP were maternal age (P = 0.007) and monthly income (P = 0.013), IPTp-SP use in preceding pregnancy (P = 0.001), and the treatment for malaria in index pregnancy (P = 0.014). On logistic regression, maternal age Conclusion: Parturients desire IPTp-SP, but the prescription rate by healthcare providers was low. Healthcare providers should increase the prescription and address the concerns about its teratogenicity. Governments and other agencies should prioritize free provision and the availability of SP at health facilities.

Scheduled Intermittent Screening with Rapid Diagnostic Tests and Treatment with Dihydroartemisinin-Piperaquine versus Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine for Malaria in Pregnancy in Malawi: An Open-Label Randomized Controlled Trial.

BackgroundIn Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP.Methods and FindingsThis was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the intermittent screening and treatment in pregnancy with DP (ISTp-DP) arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk]) in paucigravidae (first or second pregnancy) and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher). Analysis was by intention to treat.Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae). The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9%) and IPTp-SP (28.8%) arms (risk difference = 1.08% [95% CI −3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90–1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92–1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71–1.20], p = 0.543). The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference = 7.85%, [95% CI 3.07%–12.63%]; all women: RR = 1.19 [95% CI 1.07–1.33], p = 0.007; paucigravidae: RR = 1.16 [95% CI 1.04–1.31], p = 0.011; multigravidae: RR = 1.29 [95% CI 1.02–1.63], p = 0.037). Fetal loss was more common with ISTp-DP (2.6% versus 1.3%; RR = 2.06 [95% CI 1.01–4.21], p = 0.046) and highest among non-DP-recipients (3.1%) in the ISTp-DP arm. Limitations included the open-label design.ConclusionsScheduled screening for malaria parasites with the current generation of RDTs three to four times during pregnancy as part of focused antenatal care was not superior to IPTp-SP in this area with high malaria transmission and high SP resistance and was associated with higher fetal loss and more malaria at delivery.Trial RegistrationPan African Clinical Trials Registry PACTR201103000280319; ISRCTN Registry ISRCTN69800930

Rapid Diagnostic Test Performance Assessed Using Latent Class Analysis for the Diagnosis of Plasmodium falciparum Placental Malaria.

Placental malaria causes low birth weight and neonatal mortality in malaria-endemic areas. The diagnosis of placental malaria is important for program evaluation and clinical care, but is compromised by the suboptimal performance of current diagnostics. Using placental and peripheral blood specimens collected from delivering women in Malawi, we compared estimation of the operating characteristics of microscopy, rapid diagnostic test (RDT), polymerase chain reaction, and histopathology using both a traditional contingency table and a latent class analysis (LCA) approach. The prevalence of placental malaria by histopathology was 13.8%; concordance between tests was generally poor. Relative to histopathology, RDT sensitivity was 79.5% in peripheral and 66.2% in placental blood; using LCA, RDT sensitivities increased to 93.7% and 80.2%, respectively. Our results, if replicated in other cohorts, indicate that RDT testing of peripheral or placental blood may be suitable approaches to detect placental malaria for surveillance programs, including areas where intermittent preventive therapy in pregnancy is not used.

The challenge of using intermittent preventive therapy with sulfadoxine/pyrimethamine among pregnant women in Uganda

BackgroundThe Uganda National Malaria Control Programme recommends the use of intermittent preventive therapy in pregnancy with sulfadoxine/pyrimethamine (SP) to prevent malaria, however, there is overwhelming evidence of low uptake of this intervention. This study, therefore, sought to examine the factors associated with taking two or more doses of therapy among women who had had the most recent live birth.MethodsThis was a secondary data analysis of the 2014 Malaria Indicator Survey dataset. The outcome was the use of two or more doses of SP for the most recent live birth while independent variables included; age, highest education attained, residence (rural and urban), use of radio and community health teams for malaria related messages, knowledge of taking SP and use of LLINS to prevent malaria, household wealth, skilled attendant seen at ANC and number of children the woman has.ResultsOf the 1820 women included in the final analysis, 822 (45.16 %) women took two or more doses of SP. Women who knew that this therapy was used to prevent malaria and those who had been seen by a skilled attendant were 10.72 times [Adjusted OR (95 % CI): 10.72 (7.62–15.08), p-value = 0.001] and 3.19 times [Adjusted OR (95 % CI): 3.19 (1.26–8.07), p-value = 0.015] more likely to take at least two doses as compared to those who did not know about this therapy and those seen by unskilled attendants, respectively.ConclusionThis study shows that knowledge among women that SP is a medication used for malaria prevention during pregnancy increases the uptake of two or more doses of this therapy among pregnant women. This highlights the importance of behaviour change communication focused on IPTp uptake that can be complemented by having skilled personnel attending to pregnant women at the antenatal clinic.

Impact of the WHO Technical Support Towards Malaria Elimination in Zambia

Background: Zambia's National Malaria Strategic Plan (NMSP) 2011-2016 aims to eliminate malaria by the year 2020. The WHO Country Office is supporting Zambia in its goal to attain this national target earlier than the global goal contained in Global Technical Strategy (GTS) 2016- 2030. WHO's focus is to accelerate coverage of proven interventions and strategies, and promote their effective use. This study documents impact of the WHO technical support in Zambia to accelerate efforts towards elimination of malaria.Methods: This study involved a desk review of relevant documents and literature to obtain in-depth information on WHO technical support on malaria. Key documents included: malaria strategic plans, World Malaria Reports (WMR), WHO Annual Reports; Country Cooperation Strategy, for WHO in Zambia; and Health Bulletins and Health Management Information System (HMIS).Results: WHO contributed effectively to monitoring malaria trends. Malaria deaths reduced from 6000 in 2010 to 3,200 in 2014. In 2015, ownership of long lasting insecticide treated nets (LLINs) increased from 38% in 2006 to 77% in 2015; to be among the highest in Africa. Similarly, utilization of LLINs increased from 19% in 2006 to 55% in 2015 and use of Intermittent Preventive Therapy in pregnancy (IPTp) increased from 61.2% in 2006 to 77% in 2015. In 2014, WHO contributed to the revision of the national malaria diagnosis and treatment guidelines that included: Dihydroartemisinin piperaquine (DHA-PQ) as first line, an alternative to Artemether lumefantrine (AL); injectable Artesunate for treatment of severe malaria and the adoption of the new WHO guidelines on IPTp. In 2016, WHO contributed to epidemiological profile leading to the development of the novel Malaria Elimination Strategy 2017-2020.Discussion: WHO support has led to the determination of epidemiological profile and contributed to the improved focusing of interventions and surveillance activities for greater impact. These have been supported by clear guidelines on proven and evidenced-based prevention, diagnosis and treatment strategies.Conclusion: WHO's technical assistance to priority areas in Zambia remains pivotal for the accelerated health gains countrywide. The importance of this technical support is evidenced in the malaria elimination strategy within an environment of changing epidemiological malaria profile, insecticide and drug resistance.

Knowledge, attitude and practice on malaria prevention and sulfadoxine-pyrimethamine utilisation among pregnant women in Badagry, Lagos State, Nigeria.

Malaria in pregnancy is one of the major causes of mater nal morbidity and mortality as well as of poor pregnancy outcomes. We studied the knowledge, attitude and practices of pregnant women on malaria prevention, assessed their knowledge of sulfadoxine-pyrimethamine (SP) for intermittent preventive therapy in pregnancy (IPTp-SP), and used the outcomes to create awareness on malaria prevention with IPTp-SP. A structured questionnaire on malaria prevention and SP utilisation was administer ed to 450 pregnant women attending antenatal clinics in both government and private health facilities in Badagry, Lagos State, Nigeria. 355 (78.8% ) of the pregnant women perceived malaria as a serious illness. Other responses by the respondents included: parasitic disease (13; 2.9%); caused by mosquito (5; 1.9%), while 77 (17%) said they did not know. The signs and symptoms of malaria mentioned included headache (109; 24.2%), weakness (77; 17.1%), fever (77; 17.1%) and body pains (44; 10%). 174 (58%) women indicated that they would go to a hospital when having malaria, 54 (17%) indulged in self-medication, while 32 (11%) took herbs. 43 (14%) did nothing. Malaria prevention was performed by taking herbs (134; 30%); artemisinin-based combination therapy (ACT) (123; 27%); daraprim (104; 23%); blood tonic (51; 11%); paracetamol (21; 5%) and SP (17; 4%). Mosquito control was mainly carried out by the use of insecticide spray (215; 47.7%), followed by anti-mosquito coils (95; 21%). Out of the 450 pregnant women interviewed, 350 (84.5%) said that SP was for the treatment of malaria, while 69 (15.2%) said that it was for malaria prevention. Knowledge of SP was influenced by both education (P<0.05) and parity (P<0.001). The majority of the pregnant women had knowledge of SP but did not know that it is used for malaria prevention. Most of the respondents took malaria-preventive measures by taking herbs but preferred to go to the hospital when suspecting that they had malaria.

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

Creative solutions to extraordinary challenges in clinical trials: methodology of a phase III trial of azithromycin and chloroquine fixed-dose combination in pregnant women in Africa

BackgroundMalaria in pregnancy is one of the most common preventable causes of maternal and neonatal morbidity and mortality in sub-Saharan Africa. To prevent its adverse effects, such as maternal anaemia, placental parasitaemia and low birth weight (LBW) neonates, the World Health Organization recommends effective malaria case management, use of insecticide-treated bed nets and intermittent preventive therapy in pregnancy (IPTp). Sulphadoxine-pyrimethamine (SP) has been the standard for IPTp in several countries, but parasite resistance to SP is growing. Therefore, new IPTp therapies are urgently needed. One candidate being evaluated for IPTp is a fixed-dose combination of azithromycin and chloroquine (AZCQ). This paper describes the challenges and the innovative solutions implemented in designing and conducting a pivotal AZCQ-IPTp trial, sponsored by Pfizer Inc and co-funded by Pfizer Inc and the Medicines for Malaria Venture.MethodsThe AZCQ-IPTp pivotal trial is a multicentre, multicountry, phase III, open-label, randomized superiority study of AZCQ-IPTp versus SP-IPTp in pregnant women of sub-Saharan Africa. The trial was designed to meet stringent regulatory agency scientific advice and IPTp policy makers’ recommendations, and incorporates an innovative adaptive design to manage programme risk, maintain the operating characteristics of the study and optimize resources. The trial’s novel composite primary endpoint is the proportion of participants with a suboptimal pregnancy outcome (abortion [≤28 weeks], stillbirths [>28 weeks], premature [<37 weeks] deliveries, LBW [<2,500 g] live neonates, missing neonatal birth weight data or loss to follow-up). The study employs a prospective group sequential design with three unblinded analyses when 50%, 70% and 100% of participants achieve the primary endpoint; the study team will remain blinded to the analyses until after the completion of the study. The number of participants randomized will be adaptive, based on the blinded review of the observed pooled primary endpoint data across the two treatment arms, when approximately 1,000 participants complete the primary endpoint assessments.ResultsThis study is ongoing and expected to complete in 2014.ConclusionThis report describes the unique challenges and innovative solutions implemented in designing and conducting this pivotal AZCQ-IPTp trial, which may serve as a prototype for future IPTp and other studies involving similar conditions.

Weighing for results: assessing the effect of IPTp

Although earlier studies showed that intermittent preventive therapy in pregnancy (IPTp) with sulfadoxine–pyrimethamine provides substantial benefit to pregnant women and their infants, the spread of resistance raises questions about how long the therapy is efficient for.1 In their meta-analysis, Thomas Eisele and colleagues2 show that IPTp with sulfadoxine–pyrimethamine continues to provide substantial benefits, resulting in a 26% reduction in low birthweight and a 16% reduction in neonatal mortality under programme conditions.