Intermittent Preventive Treatment Of Malaria In Pregnancy Research Articles

Impact of Malaria Interventions on Anaemia amongst Pregnant Women in Ghana: A Secondary Analysis of Data

Abstract Background: There is limited published literature available on the impact of insecticide-treated nets (ITNs) and sulphadoxine-pyrimethamine (Sp) as an intermittent preventive treatment for malaria in pregnancy (IPTp) on anaemia amongst pregnant women in Ghana. Materials and Methods: The data from the United States Agency for International Development Malaria Indicator Survey in Ghana for 2016 and 2019 was used and analysed. Key variables, including anaemia status, ITN usage and IPTp-Sp uptake, were analysed using descriptive statistics, Chi-square and logistic regression. Results: The pregnant women who took IPTp-Sp had a 17% lower likelihood of anaemia compared to non-users. In 2019, with increased ITN usage at 57.1%, anaemia prevalence decreased to 54.5%. Pregnant women combining ITN use and IPTp uptake had a 96% lower likelihood of anaemia than those who did not. The women aged 30–39 and ≥40 being 53%–69% less likely to be anaemic, respectively, than those <20 years (adjusted odds ratio = 0.47 [95% confidence interval: 0.27–0.79]). Education, parity and socio-economic status also influence anaemia risk. Conclusion: IPTp-Sp usage reduced anaemia risk in pregnancy. Combining ITN use and IPTp further decreased anaemia likelihood. Enhancing the uptake of these interventions amongst pregnant women is crucial for improving maternal health outcomes. The findings have relevance for malaria-endemic countries.

Safety and tolerability of repeated doses of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a systematic review and an aggregated data meta-analysis of randomized controlled trials

BackgroundMalaria infection during pregnancy is an important cause of maternal and infant mortality and morbidity with the greatest effect being concentrated in sub-Saharan Africa. In areas of moderate to high malaria transmission, the World Health Organization (WHO) recommends the administration of intermittent preventive treatment of malaria in pregnancy (IPTp) using sulfadoxine-pyrimethamine (SP) to be given to all pregnant women at each scheduled antenatal care visit at monthly intervals. However, there is concern that increased resistance has compromised its effectiveness. This has led to a need for evaluation of alternatives to SP for IPTp with dihydroartemisinin-piperaquine (DP) emerging as a very promising candidate. Thus, this systematic review and aggregated data meta-analysis was conducted to establish the safety and tolerability of repeated doses with DP in IPTp.MethodsA systematic review and aggregated data meta-analysis of randomized controlled trials (RCTs) was performed by searching electronic databases of PubMed, Science Direct, ClinicalTrials.gov and Google Scholar. RCTs comparing IPTp DP versus recommended standard treatment for IPTp with these outcome measures were analyzed; change in QTc interval, serious adverse events (SAE), grade 3 or 4 adverse events possibly related to study drug and vomiting within 30 min after study drug administration. The search was performed up to 24th June 2023. Data was extracted from eligible studies and an aggregated data meta-analysis was carried out with data pooled as risk ratio (RR) with a 95% confidence interval (CI), using RevMan software (5.4). This study is registered with PROSPERO, CRD42022310041.ResultsSix RCTs involving 7969 participants were included in this systematic review and aggregated data meta-analysis. The pooled analysis showed that DP was associated with a change from baseline of the QTc interval although this change was not associated with cardiotoxicity. There was no statistically significant difference in the risk of occurrence of SAEs among participants in both treatment groups (RR = 0.80, 95% CI [0.52–1.24], P = 0.32). However, significant difference was observed in grade 3 or 4 AEs possibly related to study drug where analysis showed that subjects on IPT DP were statistically significantly more likely to experience an AE possibly related to study drug than subjects on IPT SP (RR = 6.65, 95% CI [1.18–37.54], P = 0.03) and in vomiting within 30 min after study drug administration where analysis showed that the risk of vomiting is statistically significantly higher in subjects receiving IPT DP than in subjects receiving IPT SP (RR = 1.77, 95% CI [1.02–3.07], P = 0.04).ConclusionDP was associated with a higher risk of grade 3 or 4 AEs possibly related to study drug and a higher risk of vomiting within 30 min after study drug administration. However, these were experienced in a very small percentage of women and did not affect adherence to study drugs. DP was also better tolerated in these studies as compared to most alternatives that have been proposed to replace SP which have proved to be too poorly tolerated in IPTp use.

Using Andersen’s behavioral model of health care use for intermittent preventive treatment of malaria in pregnancy in Nigeria

BackgroundStudies in Nigeria and elsewhere in sub-Saharan Africa (sSA) have explored factors influencing usage of intermittent preventive treatment of malaria in pregnancy (IPTp). Most studies, however, are not model or theory-based, which provides less satisfactory guidance to malaria control programming. This study fills the knowledge gap by adapting Andersen’s behavioral model of health care use to IPTp usage in Nigeria.MethodsThis study adopted a cross-sectional design that utilized secondary data extracted from the 2018 Nigeria Demographic and Health Survey (NDHS). A weighted sample of 4,772 women who had given birth in the past year preceding the survey, was analyzed. Outcome variable was usage of IPTp, dichotomized into optimal or otherwise. Explanatory variables cut across individual and community levels and were divided into predisposing, enabling and need factors in line with the theoretical constructs of the Andersen model. Two multilevel mixed-effects logistic regression models were fitted to identify factors which influenced optimal usage of IPTp. Analyses were performed using STATA 14. Statistical significance was set at 5%.ResultsRealised level of optimal IPTp usage was 21.8%. Factors that either predispose or enable pregnant women to take optimal doses of IPTp were maternal education, being employed, being autonomous in their own healthcare, health insurance enrolment, partner education, receiving antenatal care in public health facilities, rural residence, being resident in northern geo-political zones, community literacy level and community perception of the consequences of malaria. Two significant need factors affecting optimal usage of IPTp were timing of the first antenatal care visit and sleeping under mosquito bed nets.ConclusionOptimal usage of IPTp is low among pregnant women in Nigeria. There is a need to devise additional public health educational programs promoting IPTp usage through the formation of Advocacy, Communication and Social Mobilisation (ACSM) in every ward in all local government areas, particularly in the rural and northern parts of the country. In addition, health planners should adopt the Andersen model for assessing key determinants of IPTp usage among childbearing women in Nigeria.

The impact of community delivery of intermittent preventive treatment of malaria in pregnancy on its coverage in four sub-Saharan African countries (Democratic Republic of the Congo, Madagascar, Mozambique, and Nigeria): a quasi-experimental multicentre evaluation

Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine is recommended at each antenatal care clinic visit in high-moderate transmission areas. However, its coverage remains unacceptably low in many countries. Community health workers can effectively deliver malaria preventive interventions. The aim of this study was to assess the effect of community delivery of IPTp (C-IPTp) on antenatal care and IPTp coverage. A community-based IPTp administration approach was implemented in four sub-Saharan countries: the Democratic Republic of the Congo (DR Congo), Madagascar, Mozambique, and Nigeria. A quasi-experimental before and after evaluation by cluster sampling was designed where C-IPTp was implemented in selected country areas in different phases. Baseline (before C-IPTp implementation), midline, and endline household surveys were carried out to assess IPTp intake in pregnant women in 2018, 2019, and 2021. Eligible participants of the household survey were women of reproductive age (13-50 years old, depending on the country) that had a pregnancy that ended (any pregnancy regardless of pregnancy outcome) in the 6 months before the interview. For the first baseline surveys, the target population was women who had a pregnancy that ended in the 12 months before the interview. The primary outcome from the household surveys was the proportion of women who reported having received at least three doses of IPTp during pregnancy. The trial is registered at ClinicalTrials.gov, NCT03600844. A total of 32 household surveys were conducted between March 15, and Oct 30, 2018, and data from 18 215 interviewed women were analysed. The coverage of at least three doses of IPTp (IPTp3+) increased after the first year of C-IPTp implementation in all project areas in DR Congo (from 22·5% [170/755] to 31·8% [507/1596]), Madagascar (from 17·7% [101/572] to 40·8% [573/1404]), and Nigeria (from 12·7% [130/1027] to 35·2% [423/1203]), with increases between 145·6% (Madagascar) and 506·6% (Nigeria). IPTp3+ coverage increased between baseline and endline in all districts, except for Murrupula (Mozambique) and ranged between 9·6% and 533·6%. This pattern was similar in DR Congo, Madagascar, and Nigeria, and in Mozambique, the increase was lower than the other countries. Antenatal care attendance did not change or increased lightly in all study countries. C-IPTp was associated with an increase in IPTp uptake without reducing antenatal care attendance. The strategy might be considered for malaria control in pregnancy. UNITAID [2017-13-TIPTOP].

Predictors of optimal uptake of intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine and outcome of pregnancy in selected health facilities: a cross-sectional study in Northern Ghana

BackgroundGhana adopted the 2012 World Health Organization (WHO) policy on intermittent preventive treatment of malaria in pregnancy (IPTp) and implemented it in 2014 in all regions of Ghana. Despite the implementation of this policy, there has been an unacceptably low percentage of eligible women receiving the optimal dose of IPTp in Ghana which leaves millions of pregnant women unprotected from malaria. The study, therefore, assessed the predictors of three or more doses (optimal dose) of sulfadoxine-pyrimethamine (SP) in Northern Ghana.MethodsA cross-sectional study was conducted among 1188 women in four selected health facilities in Northern Ghana from September 2016 to August 2017. Information on socio-demographic and obstetric characteristics reported SP use, and maternal and neonatal outcomes were collected which was double-checked from the maternal health book as well as the antenatal care register. Pearson chi-Square and ordered logistic regression were used to determine the predictors of reported optimal SP use.ResultsOut of the 1146 women, 42.4% received 3 or more doses of IPTp-SP as recommended by the national malaria control strategy. SP uptake was significantly associated with antenatal care (ANC) attendance (aOR 0.49, 95% CI 0.36–0.66, P < 0.001), primary education (aOR 0.70, 95% CI 0.52–0.95, P = 0.022), four or more antenatal care visits (aOR 1.65, 95% CI 1.11–2.45, P = 0.014), ANC care visit in second trimester (aOR 0.63, 95% CI 0.49–0.80, P < 0.001) and third trimester (aOR 0.38, 95% CI 0.19–0.75, P = 0.006) and malaria infection during late gestation (aOR 0.56, 95% CI 0.43–0.73, p < 0.001).ConclusionThe percentage of pregnant women who received three or more doses is below the target of the National Malaria Control Programme (NMCP). The push factors for the optimal use of SP are higher educational attainment, four or more ANC visits, and early initiation of ANC. The study also confirmed earlier findings that IPTp-SP uptake of three or more doses prevents malaria in pregnancy and improves birth weight. The uptake of IPTp-SP among expectant women will be informed and increased by encouraging formal general education beyond the primary level and encouraging early initiation of ANC visits.

Molecular Determinants of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from Central Africa between 2016 and 2021: Wide Geographic Spread of Highly Mutated Pfdhfr and Pfdhps Alleles.

ABSTRACTSulfadoxine-pyrimethamine (SP) resistance impairs the efficacy of antimalarial drugs. Monitoring molecular markers in exported malaria infections provides an efficient way to trace the emergence of drug resistance in countries where malaria is endemic. Molecular markers in Pfdhfr and Pfdhps of 237 Plasmodium falciparum infections imported from central Africa between 2016 and 2021 were detected. The spatial and temporal distributions of Pfdhfr and Pfdhps mutations were analyzed. A high prevalence of Pfdhfr single-nucleotide polymorphisms (SNPs) (~92.34% to 99.10%) and a high frequency of the triple mutation haplotype I51R59N108 were observed. Cameroon, Equatorial Guinea, and Gabon showed a higher frequency (~96.61% to 100.00%) of I51R59N108 than other countries (~71.11% to 88.10%). The prevalence of C59R and I51R59N108 increased while that of other SNPs or haplotypes did not fluctuate greatly from 2016 to 2021. Large proportions of Pfdhps SNPs (A437G and K540E) were demonstrated. The SNP distribution of Pfdhps differed between countries, with S436A dominating in northern countries and A437G dominating in others. The proportions of I431V, A437G, and the triple mutant haplotype declined between 2016 and 2021, whereas the prevalence of the single mutant haplotype rose from 61.60% to 73.68%. Combinations of Pfdhfr-Pfdhps alleles conferring partial resistance, full resistance, and superresistance to SP, as defined in the text, were detected in 63.64%, 8.64%, and 0.91% of the samples, respectively. The octuple Pfdhfr-Pfdhps allele (I51R59N108-V431A436G437K540G581S613) was seen in 5.00% of the samples. We demonstrated the wide geographic spread and increasing trends in highly SP-resistant Pfdhfr genes and varying spatial patterns of Pfdhps mutants across countries in central Africa. The high prevalences of partially resistant, fully resistant, and superresistant Pfdhfr-Pfdhps combinations observed here indicated impaired SP efficacy. Increased molecular surveillance is required to monitor the changing status of the Pfdhfr and Pfdhps genes.IMPORTANCE Monitoring drug resistance is important for malaria control because its early detection enables timely action to prevent its spread and mitigate its impact. The wide geographic spread and the increasing trend of highly resistant Pfdhfr genes between 2016 and 2021 found in our study are worrisome and emphasize the urgency to monitor their updated status in central Africa. This study also illustrated the wide spread of the novel mutant Pfdhps I431V as well as the high prevalence of “partially resistant,” “fully resistant,” and “superresistant” Pfdhfr-Pfdhps combinations, indicating the urgent concern for SP efficacy in central Africa. These findings are alarming in central African countries where malaria is endemic, where SP was is widely used for the intermittent preventive treatment of malaria in pregnancy (IPTp) and the intermittent preventive treatment of malaria in infants below 5 years of age (IPTi), and urge enhanced molecular surveillance and responses to the threat of drug resistance.

Determinants of Intermittent Preventive Malaria Therapy Among Pregnant Women in A Nigerian Teaching Hospital

Background: Intermittent Preventive Treatment of malaria in Pregnancy (IPTp) is mostly issued in most antenatal clinics across the country but there have been reports of poor utilization of this prophylaxis. Objective: This study assessed the determinants of IPTp among pregnant women attending a tertiary hospital in southeast Nigeria. Methods: The study was a descriptive cross-sectional study in which a self-administered questionnaire was distributed to 250 pregnant women receiving antenatal care in the study hospital. The data collected were analyzed with the aid of SPSS, using descriptive and inferential statistics. A p-value of less than 0.05 was considered significant. Results: A majority of the participants responded positively to most of the factors assessed, however, none was statistically significant. Conclusion: Based on these findings, pregnant women at a tertiary hospital in southeast Nigeria are aware of IPTp, nevertheless, most fail to commence the medication at the correct time.

A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial.

BackgroundInnovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women.Methods and findingsThis was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020.Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention.ConclusionsIn this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context.Trial registrationClinicalTrials.gov NCT03079388.

Community-based delivery of intermittent preventive treatment of malaria in pregnancy in Burkina Faso: a qualitative study

BackgroundBurkina Faso is among ten countries with the highest rates of malaria cases and deaths in the world. Delivery and coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) is insufficient in Burkina Faso; In a 2016 survey, only 22% of eligible women had received their third dose of IPTp. It is also an extremely rural country and one with an established cadre of community healthcare workers (CHWs). To better meet the needs of pregnant women, an enhanced programme was established to facilitate distribution of IPTp at the community level by CHWs.MethodsIn order to assess the perceptions of CHWs and facility healthcare workers (HCWs) involved in this programme rollout, semi-structured interviews were conducted at three high malaria burden health districts in Burkina Faso. Interviews were conducted at baseline with 104 CHWs and 35 HCWs prior to the introduction of community based IPTp (c-IPTp) to assess capacity and any areas of concern. At endline, interviews were conducted with 29 CHWs and 21 HCWs to identify key facilitators and suggestions for further implementation of the c-IPTp programme.ResultsCHWs reported feeling capable of supporting c-IPTp delivery and facilitating linkage to antenatal care (ANC). They noted that the opportunity for enhanced training and close and ongoing connections with facility HCWs and supportive supervision were imperative. Both CHWs and HCWs perceived this approach as acceptable to community members and noted the importance of close community engagement, monthly meetings between CHWs and facility HCWs, and maintaining regular supplies of sulfadoxine–pyrimethamine (SP). Those interviewed noted that it was beneficial to have the involvement of both female and male CHWs.ConclusionsCommunity-based delivery of IPTp was feasible and acceptable to both facility HCWs and CHWs. This approach has the potential to strengthen delivery and uptake of IPTp and ANC both in Burkina Faso and across the region.

Participatory research for the development of information, education and communication tools to promote intermittent preventive treatment of malaria in pregnancy in the Democratic Republic of the Congo, Nigeria and Mozambique

BackgroundTo improve the coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) in Africa, Medicines for Malaria Venture (MMV) developed, tested and validated a new packaging of sulfadoxine–pyrimethamine (SP), as well as specific communications tools designed to improve knowledge of IPTp and the motivation of women to adhere to it, particularly if it is distributed by community health workers (CHW).MethodsThis article describes and analyses the results of an empirical research carried out in the Democratic Republic of the Congo (DRC), Nigeria and Mozambique, to evaluate the perception and social acceptability of SP for healthcare providers, CHW and pregnant women, and to assess the ability of the new SP packaging and the communications tools to change their perception of SP and improve their attitudes towards IPTp.ResultsThe results indicate that SP’s new individual packaging was perceived by pregnant women and healthcare providers as a “hygienic” and “safe”, with a specific identity. The graphics used in IPTp communications tools were modified according to the respondents’ feedback to make them more culturally and socially sensitive, and then validated. However, although the new blister packaging and IPTp communications tools generated greater confidence and motivation, SP side effects as well as preconceived ideas, particularly regarding its efficacy, remain a challenge that must be addressed to improve IPTp acceptance and compliance by healthcare providers and pregnant women.ConclusionThis participatory approach to social research based on ongoing feedback to the graphic designer provided more empirical evidence to improve and adapt the textual and visual content of communication tools (SP blister packaging, leaflet, user guide) to local contexts and user preferences. Tested and validated in different socio-cultural and socio-political contexts, these tools provide a good basis for the promotion of IPTp in Africa.

Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique

In 2005, the Nigerian Federal Ministry of Health revised the treatment policy for uncomplicated malaria with the introduction of artemisinin-based combination therapies (ACTs). This policy change discouraged the use of Sulphadoxine-pyrimethamine (SP) as the second-line treatment of uncomplicated falciparum malaria. However, SP is used as an intermittent preventive treatment of malaria in pregnancy (IPTp) and seasonal malaria chemoprevention (SMC) in children aged 3–59 months. There have been increasing reports of SP resistance especially in the non-pregnant population in Nigeria, thus, the need to continually monitor the efficacy of SP as IPTp and SMC by estimating polymorphisms in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes associated with SP resistance. The high resolution-melting (HRM) assay was used to investigate polymorphisms in codons 51, 59, 108 and 164 of the dhfr gene and codons 437, 540, 581 and 613 of the dhps gene. DNA was extracted from 271 dried bloodspot filter paper samples obtained from children (< 5 years old) with uncomplicated malaria. The dhfr triple mutant I51R59N108, dhps double mutant G437G581 and quadruple dhfr I51R59N108 + dhps G437 mutant haplotypes were observed in 80.8%, 13.7% and 52.8% parasites, respectively. Although the quintuple dhfr I51R59N108 + dhps G437E540 and sextuple dhfr I51R59N108 + dhps G437E540G581 mutant haplotypes linked with in-vivo and in-vitro SP resistance were not detected, constant surveillance of these haplotypes should be done in the country to detect any change in prevalence.

Study protocol of a cluster randomized controlled trial of strategies to increase antenatal iron and folic acid supplementation and malaria prophylaxis in rural south-central C\xf4te d\u2019Ivoire

BackgroundCoverage of antenatal iron and folic acid supplementation (IFAS) and intermittent preventive treatment of malaria in pregnancy (IPTp) remains low in many countries. Evidence on the most effective ways to increase both IFASIPTp is mixed overall, with only few studies directly identifying cost-effective ways to increase coverage of both interventions. The proposed study aims to assess the cost, impact and relative cost-effectiveness of two complementary strategies of increasing IFAS and malaria chemoprophylaxis coverage among pregnant women relative to the current default system in a rural low-income setting of sub-Saharan Africa.Methods/designThis study will be carried out in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d’Ivoire. This is a cluster-randomized trial targeting 720 consenting pregnant women aged ≥15 years. The 118 clusters constituting the Taabo HDSS monitoring area will be randomly allocated to one of the following three groups with equal probability: a control group, an information only group, and an information plus home delivery group. To assess the relative effectiveness of each strategy, we will conduct an endline survey within the first 2 weeks after delivery. The primary outcomes of the trial will be maternal post-partum anaemia and malaria infection. Anaemia will be assessed using HEMOCUE devices; malaria infections will be assessed using standard rapid diagnostic tests named CareStart™ Malaria Pf (HRP2) Ag RDT (Multi Kit with capped lancet and inverted cup specimen transfer device). Other outcomes will include self-reported adherence to supplementation and malaria chemoprophylaxis, as well as miscarriages, stillbirths and low birth weight deliveries.DiscussionThis study will assess the cost-effectiveness of two alternative strategies to increase antenatal IFAS and malaria chemoprophylaxis coverage among pregnant women in rural Côte d’Ivoire and similar settings.Trial registrationClinicalTrials.govNCT04250428; Registered 31 January 2020.

Determinants of Uptake of Intermittent Preventive Treatment for Malaria among Pregnant Women in Suba Sub-County, Homabay County, Kenya

Background: Intermittent preventive treatment of malaria in pregnancy (IPTp) is one of the effective and efficacious interventions recommended for prevention of malaria in pregnancy. The drug of choice is Sulphadoxine-Pyrimethamine (SP) and Kenya adopted the use of IPTp in line with revised 2012 recommendation by WHO. Method: A cross sectional study was carried out in Suba Sub County to established determinants of uptake of IPTp, from July 2017 to December 2019. The target population was women of reproductive age (15-49 years old) who had live births two years preceding the study and who visited ANC clinic. All health facilities providing ANC services were purposively selected and stratified Systematic random sampling technique was used to sample the mothers who had given birth during the last 24 months from ANC clients register. Quantitative data collection was carried out using questionnaires that were administered to respondents. All mother –child booklets were checked to confirm whether the respondent received IPTp during her last pregnancy. Results: A total of 382 women who had live births two years prior to the study and who sought ANC services were interviewed. The study revealed that 59.5 % of respondents received three or more doses of IPTp-SP, with 17.2% receiving at least one dose. Women who attended ANC clinic three or more times had a higher odds of receiving three or more doses of IPTp-SP (OR=1.0), compared with women who attended clinic less than three times (OR=0.04).Women who stayed six or more Km away from health facility were less likely to receive three or more doses of IPTp-SP (OR=0.21). Women who took 30 or more minutes to reach health facility were most likely to receive three or more doses of IPTp –SP (OR=2.93) compared with women who took less than 30 minutes. Conclusion: T he study revealed that majority of pregnant women attended ANC clinic three or more times and not all women interviewed received the recommended three or more doses of IPTp.

Coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) influences delivery outcomes among women with obstetric referrals at the district level in Ghana

BackgroundThe aim of the study was to determine the coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) and its relationship with delivery outcomes among obstetric referral cases at the district level of healthcare.MethodsAn implementation research within three districts of the Greater Accra region was conducted from May 2017 to February 2018, to assess the role of an enhanced inter-facility communication system on processes and outcomes of obstetric referrals. A cross-sectional analysis of the data on IPTp coverage as well as delivery outcomes for the period of study was conducted, for all the referrals ending up in deliveries. Primary outcomes were maternal and neonatal complications at delivery. IPTp coverage was determined as percentages and classified as adequate or inadequate. Associated factors were determined using Chi square. Odds ratios (OR, 95% CI) were estimated for predictors of adequate IPTp dose coverage for associations with delivery outcomes, with statistical significance set at p = 0.05.ResultsFrom a total of 460 obstetric referrals from 16 lower level facilities who delivered at the three district hospitals, only 223 (48.5%) received adequate (at least 3) doses of IPTp. The district, type of facility where ANC is attended, insurance status, marital status and number of antenatal clinic visits significantly affected IPTp doses received. Adjusted ORs show that adequate IPTp coverage was significantly associated with new-born complication [0.80 (0.65–0.98); p = 0.03], low birth weight [0.51 (0.38–0.68); p < 0.01], preterm delivery [0.71 (0.55–0.90); p = 0.01] and malaria as indication for referral [0.70 (0.56–0.87); p < 0.01]. Positive association with maternal complication at delivery was seen but was not significant.ConclusionIPTp coverage remains low in the study setting and is affected by type of health facility that ANC is received at, access to health insurance and number of times a woman attends ANC during pregnancy. This study also confirmed earlier findings that, as an intervention IPTp prevents bad outcomes of pregnancy, even among women with obstetric referrals. It is important to facilitate IPTp service delivery to pregnant women across the country, improve coverage of required doses and maximize the benefits to both mothers and newborns.

Prevalence of asymptomatic Plasmodium falciparuminfection, anaemia and use of ITNs among pregnant women yet to receive IPTp in parts of southern Ghana

Background: Asymptomatic malaria in pregnancy evades most fever-based surveillance systems yet causes significant morbidities such as anaemia in the pregnant woman and low birth weight in the neonate. Objective:This study determined the prevalence of asymptomatic malaria and its association with anaemia among pregnant women who are yet to receive their first dose of Sulphadoxine-Pyrimethamine (SP) as intermittent preventive treatment of malaria in pregnancy (IPTp). Information on the use of insecticide treated nets(ITNs)as vector control by the pregnant women was also sought. Methods: This is a cross-sectional hospital-based study conducted in the Western Region of Ghana. Pregnant women at gestational ages, 16-26 wkwere included. A structured questionnaire was used to collect vital information from the participants. Plasmodiumparasitaemia was determined by rapid diagnostic test (MRDT), microscopy and species-specific nested polymerase chain reaction (PCR). Anaemia was classified using the level of haemoglobin. Results: A total of 413 antenatal clinic attendants were recruited. Prevalence of asymptomatic Plasmodium falciparuminfection was 13.1% by MRDT, 10.1% by microscopy and 13.8% by PCR. The mean haemoglobin was 10.73g/dL. Prevalence of anaemia was 40.49% and the mean parasite density was 149.6 parasite/μL. Pregnant women with asymptomatic malaria were 4 times more at risk of being anaemic (adjusted odds ratio with 95% confidence interval: 4.42, 1.82 -10.70)than those who did not have malaria. There was statistically significant negative correlation between parasite density and anaemia (r=0.0028, p=0.02). Conclusion: Asymptomatic P. falciparuminfection was found among some of the pregnant women and the presence of the parasites make them 4 times at increased risk of developing anaemia. Anaemia when occurring amongst such women was significantly worsened by increasing parasitaemia.

Mathematical Model of Controlling the Spread of Malaria Disease Using Intervention Strategies

This paper proposes and analyses a basic deterministic mathematical model to investigate Simulation for controlling the spread of malaria Diseases Transmission dynamics. The model has seven non-linear differential equations which describe the control of malaria with two state variables for mosquito’s populations and five state variables for human’s population. To represent the classification of human population we have included protection and treatment compartments to the basic SIR epidemic model and extended it to SPITR model and to introduce the new SPITR modified model by adding vaccination for the transmission dynamics of malaria with four time dependent control measures in Ethiopia Insecticide treated bed nets (ITNS), Treatments, Indoor Residual Spray (IRs) and Intermittent preventive treatment of malaria in pregnancy (IPTP). The models are analyzed qualitatively to determine criteria for control of a malaria transmission dynamics and are used to calculate the basic reproduction R0. The equilibria of malaria models are determined. In addition to having a disease-free equilibrium, which is globally asymptotically stable when the R0<1, the basic malaria model manifest one's possession of (a quality of) the phenomenon of backward bifurcation where a stable disease-free equilibrium co-exists (at the same time) with a stable endemic equilibrium for a certain range of associated reproduction number less than one. The results also designing the effects of some model parameters, the infection rate and biting rate. The numerical analysis and numerical simulation results of the model suggested that the most effective strategies for controlling or eradicating the spread of malaria were suggest using insecticide treated bed nets, indoor residual spraying, prompt effective diagnosis and treatment of infected individuals with vaccination is more effective for children.

High uptake of Intermittent Preventive Treatment of malaria in pregnancy is associated with improved birth weight among pregnant women in Ghana

Despite the clinically proven advantages of intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), utilisation has been low in many African countries. To increase uptake and achieve the desired effect, the World Health Organization revised the policy to a monthly administration. Assessing the coverage and impact of the revised policy on pregnancy and neonatal outcomes is, therefore, a necessity. A 2-parallel cross-sectional hospital-based study was carried out among pregnant women attending first antenatal care (ANC) and delivery. Maternal and cord blood samples were assayed for malaria parasites by quantitative PCR targeting both the 18S rDNA and the acidic terminal segment of Plasmodium falciparum var genes, and plasma SP levels were measured by liquid chromatography coupled to tandem mass spectrometry. Parasite prevalence was similar between the two study sites but decreased significantly between the first ANC (9% or 43%) and delivery (4% or 11%) based on the qPCR target. At delivery, 64.5% of women received ≥3 IPTp-SP dose, 15.5% received 2 doses and 6% had 1 dose. Taking ≥3 IPTp-SP doses was associated with an average birth weight increase of more than 0.165 kg. IPTp-SP uptake was associated with plasma SP level at delivery (OR = 32.3, p ≤ 0.005, 95% CI (13.3;78.4) for those that reported ≥3 IPTp-SP doses) while the same trend of improved birth weight was observed with high plasma SP levels. The new IPTp policy is well implemented and well utilised by women in the sites considered in this study and translates to the improved birth weight observed. This study confirms the interest and the clinical benefit expected from this policy change.

Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda.

Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria. Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12 to 20 weeks gestation through delivery. Multivariate analysis was used to measure associations between characteristics of parasitemia during pregnancy and the risk of placental malaria based on histopathology. Overall risk of placental malaria was 44.6%. None of the 34 women without parasitemia detected during pregnancy had evidence of placental malaria. Increasing proportion of interval assessments with parasitemia and higher parasite densities were independently associated with an increased risk of placental malaria. Higher gravidity and more effective IPTp were associated with a decreased risk of placental malaria. Women with parasitemia only detected before the third trimester still had an increased risk of placental malaria. The frequency, density, and timing of parasitemia are all important risk factors for placental malaria. Interventions should target the prevention of all levels of parasitemia throughout pregnancy.

Population Pharmacokinetics of Mefloquine Intermittent Preventive Treatment for Malaria in Pregnancy in Gabon.

Mefloquine was evaluated as an alternative for intermittent preventive treatment of malaria in pregnancy (IPTp) due to increasing resistance against the first-line drug sulfadoxine-pyrimethamine (SP). This study determined the pharmacokinetic characteristics of the mefloquine stereoisomers and the metabolite carboxymefloquine (CMQ) when given as IPTp in pregnant women. Also, the relationship between plasma concentrations of the three analytes and cord samples was evaluated, and potential covariates influencing the pharmacokinetic properties were assessed. A population pharmacokinetic analysis was performed with 264 pregnant women from a randomized controlled trial evaluating a single and a split-dose regimen of two 15-mg/kg mefloquine doses at least 1 month apart versus SP-IPTp. Both enantiomers of mefloquine and its carboxy-metabolite (CMQ), measured in plasma and cord samples, were applied for pharmacokinetic modelling using NONMEM 7.3. Both enantiomers and CMQ were described simultaneously by two-compartment models. In the split-dose group, mefloquine bioavailability was significantly increased by 5%. CMQ induced its own metabolism significantly. Maternal and cord blood concentrations were significantly correlated (r2 = 0.84) at delivery. With the dosing regimens investigated, prophylactic levels are not constantly achieved. A modeling tool for simulation of the pharmacokinetics of alternative mefloquine regimens is presented. This first pharmacokinetic characterization of mefloquine IPTp indicates adequate exposure in both mefloquine regimens; however, concentrations at delivery were below previously suggested threshold levels. Our model can serve as a valuable tool for researchers and clinicians to develop and optimize alternative dosing regimens for IPTp in pregnant women.

Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana.

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Sulphadoxine-pyrimethamine (SP) which was the second line antimalarial drug in Ghana, was now adopted for intermittent preventive treatment of malaria in pregnancy (IPTp). Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we employed restriction fragment length polymorphism polymerase chain reaction to genotype and compare single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter ( pfcrt, PF3D7_0709000), multidrug resistance ( pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase ( pfdhfr, PF3D7_0417200) and dihydropteroate synthase ( pfdhps, PF3D7_0810800) genes. Parasites were collected from children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) in 2012-2013 and 2016-2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10.2% and 65.1% of infections, respectively. The majority of the isolates harboured the antifolate resistance-associated pfdhfr alleles 51I (83.4%), 59R (85.9 %) and 108N (90.5%). Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G , which was more common in Accra compared to Kintampo for the 2016-2017 isolates. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination ( I 51 R 59 N 108/ G 437). CQ resistance alleles decreased during the 12 years after CQ withdrawal, but an mediate SP resistance alleles increased. Conclusion: Surveillance of the prevalence of resistance alleles is necessary in monitoring the efficacy of antimalarial drugs.