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BMJ Global Health Aug 2021Ghana adopted the revised WHO recommendation on intermittent preventive treatment in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in 2012. This study has assessed...
INTRODUCTION
Ghana adopted the revised WHO recommendation on intermittent preventive treatment in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in 2012. This study has assessed the effectiveness and safety of this policy in Ghana.
METHODS
A total of 1926 pregnant women enrolled at antenatal care (ANC) clinics were assessed for birth outcomes at delivery, and placental histology results for malaria infection were obtained from 1642 participants. Association of reduced placental or peripheral malaria, anaemia and low birth weight (LBW) in women who received ≥4 IPTp-SP doses compared with 3 or ≤2 doses was determined by logistic regression analysis.
RESULTS
Among the 1926 participants, 5.3% (103), 19.2% (369), 33.2% (640) and 42.3% (817) of women had received ≤1, 2, 3 or ≥4 doses, respectively. There was no difference in risk of active placental malaria (PM) infection in women who received 3 doses compared with ≥4 doses (adjusted OR (aOR) 1.00, 95% CI 0.47 to 2.14). The risk of overall PM infection was 1.63 (95% CI 1.07 to 2.48) in 2 dose group and 1.06 (95% CI 0.72 to 1.57) in 3 dose group compared with ≥4 dose group. The risk of LBW was 1.55 (95% CI 0.97 to 2.47) and 1.06 (95% CI 0.68 to 1.65) for 2 and 3 dose groups, respectively, compared with the ≥4 dose group. Jaundice in babies was present in 0.16%, and 0% for women who received ≥4 doses of SP.
CONCLUSION
There was no difference in the risk of PM, LBW or maternal anaemia among women receiving 3 doses compared with ≥4 doses. Receiving ≥3 IPTp-SP doses during pregnancy was associated with a lower risk of overall PM infection compared with 2 doses. As there are no safety concerns, monthly administration of IPTp-SP offers a more practical opportunity for pregnant women to receive ≥3 doses during pregnancy.
Topics: Antimalarials; Drug Combinations; Female; Ghana; Humans; Placenta; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine
PubMed: 34417272
DOI: 10.1136/bmjgh-2021-005877 -
PloS One 2021Intermittent preventive treatment of malaria among pregnant women with sulfadoxine-pyrimethamine (IPTp-SP), is one of the three recommended interventions for the...
An ethnographic study of how health system, socio-cultural and individual factors influence uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in a Ghanaian context.
BACKGROUND
Intermittent preventive treatment of malaria among pregnant women with sulfadoxine-pyrimethamine (IPTp-SP), is one of the three recommended interventions for the prevention of malaria in pregnancy (MiP) in sub-Sahara Africa. The World Health Organisation recommended in 2012 that SP be given at each scheduled ANC visit except during the first trimester and can be given a dose every month until the time of delivery, to ensure that a high proportion of women receive at least three doses of SP during pregnancy. Despite implementation of this policy, Ghana did not attain the target of 100% access to IPTp-SP by 2015. Additionally, negative outcomes of malaria infection in pregnancy are still recurring. This ethnographic study explored how health system, individual and socio-cultural factors influence IPTp-SP uptake in two Ghanaian regions.
METHODS
The study design was ethnographic, employing non-participant observation, case studies and in depth interviews in 8 health facilities and 8 communities, from April 2018 to March 2019, in two Ghanaian regions. Recommended ethical procedures were observed.
RESULTS
Health system factors such as organization of antenatal care (ANC) services and strategies employed by health workers to administer SP contributed to initial uptake. Women's trust in the health care system contributed to continued uptake. Inadequate information provided to women accessing ANC, stock-outs and fees charged for ANC services reduced access to IPTp-SP. Socio-cultural factor such as encouragement from social networks influenced utilization of ANC services and IPTp-SP uptake. Individual factors such as refusing to take SP, skipping ANC appointments and initiating ANC attendance late affected uptake.
CONCLUSION
Health system, socio-cultural and individual factors influence uptake of optimum doses of IPTp-SP. Consequently, interventions that aim at addressing IPTp-SP uptake should focus on regular and sufficient supply of SP to health facilities, effective implementation of free ANC, provision of appropriate and adequate information to women and community outreach programmes to encourage early and regular ANC visits.
Topics: Adult; Anthropology, Cultural; Antimalarials; Community Health Planning; Drug Combinations; Female; Ghana; Humans; Malaria; Pregnancy; Pregnancy Complications, Parasitic; Pregnancy Trimester, First; Pregnant Women; Prenatal Care; Preventive Health Services; Pyrimethamine; Sulfadoxine; Young Adult
PubMed: 34618812
DOI: 10.1371/journal.pone.0257666 -
Tropical Medicine & International... Jun 2006To compare the efficacies against uncomplicated falciparum malaria of chloroquine (CQ), amodiaquine (AQ), sulfadoxine-pyrimethamine (SP) and combinations of these... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To compare the efficacies against uncomplicated falciparum malaria of chloroquine (CQ), amodiaquine (AQ), sulfadoxine-pyrimethamine (SP) and combinations of these inexpensive drugs.
METHODS
We searched Medline, Embase, Cochrane CENTRAL Register of Controlled Trials, BIOSIS, Web of Science, African Index Medicus, DARE, Digital Dissertations and Current Controlled Trials for randomised or quasi-randomised controlled trials conducted between 1991 and June 2004 regardless of language and geography. We also contacted malaria experts, searched reference lists, and contacted individual authors for unreported study characteristics and additional data. Unpublished data were sought and included in the analyses.
RESULTS
Thirteen randomised trials (n = 4248) were identified and the summary relative risks of treatment failure at 28 days were calculated. There was marginal benefit in adding CQ to SP, compared with SP monotherapy (RR = 0.74, 95% CI 0.54-1.02). Combining AQ with SP was associated with a significantly lower risk of treatment failure than SP monotherapy (RR = 0.35, 95% CI 0.15-0.82) and AQ monotherapy (RR = 0.59, 95% CI 0.42-0.83). AQ plus SP was associated with a significantly lower risk of treatment failure than CQ plus SP (RR = 0.42, 95% CI 0.25-0.72). Serious adverse events were rare and did not increase with combination therapy.
CONCLUSION
Amodiaquine plus SP remains an efficacious, affordable and safe option for treating malaria in certain settings.
Topics: Amodiaquine; Antimalarials; Chloroquine; Drug Combinations; Drug Therapy, Combination; Humans; Malaria, Falciparum; Pyrimethamine; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Sulfadoxine; Treatment Failure
PubMed: 16771999
DOI: 10.1111/j.1365-3156.2006.01571.x -
Malaria Journal Jun 2012As a result of the widespread resistance to chloroquine and sulphadoxine-pyrimethamine, artemisinin-based combination therapy (ACT) (including artemether-lumefantrine...
BACKGROUND
As a result of the widespread resistance to chloroquine and sulphadoxine-pyrimethamine, artemisinin-based combination therapy (ACT) (including artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Intermittent preventive treatments with anti-malarial drugs based on sulphadoxine-pyrimethamine are also given to children or pregnant women once per month during the transmission season. Since 2006, there have been very few reports on the susceptibility of Plasmodium falciparum to anti-malarial drugs. To estimate the prevalence of resistance to several anti-malarial drugs since the introduction of the widespread use of ACT, the presence of molecular markers associated with resistance to chloroquine and sulphadoxine-pyrimethamine was assessed in local isolates at the military hospital of Dakar.
METHODS
The prevalence of genetic polymorphisms in genes associated with anti-malarial drug resistance, i.e., Pfcrt, Pfdhfr, Pfdhps and Pfmdr1, and the copy number of Pfmdr1 were evaluated for a panel of 174 isolates collected from patients recruited at the military hospital of Dakar from 14 October 2009 to 19 January 2010.
RESULTS
The Pfcrt 76T mutation was identified in 37.2% of the samples. The Pfmdr1 86Y and 184F mutations were found in 16.6% and 67.6% of the tested samples, respectively. Twenty-eight of the 29 isolates with the 86Y mutation were also mutated at codon 184. Only one isolate (0.6%) had two copies of Pfmdr1. The Pfdhfr 108N/T, 51I and 59R mutations were identified in 82.4%, 83.5% and 74.1% of the samples, respectively. The double mutant (108N and 51I) was detected in 83.5% of the isolates, and the triple mutant (108N, 51I and 59R) was detected in 75.3%. The Pfdhps 437G, 436F/A and 613S mutations were found in 40.2%, 35.1% and 1.8% of the samples, respectively. There was no double mutant (437G and 540E) or no quintuple mutant (Pfdhfr 108N, 51I and 59R and Pfdhps 437G and 540E). The prevalence of the quadruple mutant (Pfdhfr 108N, 51I and 59R and Pfdhps 437G) was 36.5%.
CONCLUSIONS
Since 2004, the prevalence of chloroquine resistance had decreased. The prevalence of isolates with high-level pyrimethamine resistance is 83.5%. The prevalence of isolates resistant to sulphadoxine is 40.2%. However, no quintuple mutant (Pfdhfr 108N, 51I and 59R and Pfdhps 437G and 540E), which is associated with a high level of sulphadoxine-pyrimethamine resistance, has been identified to date. The resistance to amodiaquine remains moderate.
Topics: Antimalarials; Chloroquine; Drug Combinations; Drug Resistance; Female; Gene Dosage; Gene Frequency; Genes, Protozoan; Hospitals, Military; Humans; Malaria, Falciparum; Male; Mutation, Missense; Plasmodium falciparum; Point Mutation; Prevalence; Pyrimethamine; Senegal; Sulfadoxine
PubMed: 22694921
DOI: 10.1186/1475-2875-11-197 -
The American Journal of Tropical... Nov 2023Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity....
Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity. As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008. Nonetheless, more recent findings suggest that SP may improve birthweight even in the face of parasite resistance, through alternative mechanisms that are independent of antimalarial effects. The prevalence of single nucleotide polymorphisms in Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda's Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction-fluorescent microsphere assay. The frequency of pfdhps K540E, A581G, and the quintuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E) and sextuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E + A581G) mutant genotypes was 90%, 38%, 75%, and 28%, respectively. No significant genotype difference was seen between the two districts, which are approximately 50 km apart. Observed agreements for matched peripheral to placental blood were reported and found to be 207 of 208 (99%) for pfdhfr and 239 of 260 (92%) for pfdhps. The peripheral blood sample did not miss any pfdhfr drug-resistant mutants or pfdhps except at the S436 loci. At this level of the sextuple mutant, the antimalarial efficacy of SP for preventing low birthweight is reduced, although overall SP still exerts a nonmalarial benefit during pregnancy. This study further reveals the need to intensify preventive measures to sustain malaria control in Rwanda to keep the overall incidence of malaria during pregnancy low.
Topics: Female; Pregnancy; Humans; Antimalarials; Plasmodium falciparum; Pregnant Women; Malaria, Falciparum; Prevalence; Rwanda; Birth Weight; Drug Resistance; Placenta; Pyrimethamine; Sulfadoxine; Drug Combinations; Malaria; Polymorphism, Single Nucleotide
PubMed: 37783456
DOI: 10.4269/ajtmh.23-0225 -
Antimicrobial Agents and Chemotherapy Oct 2004The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric... (Clinical Trial)
Clinical Trial
The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric modeling analysis. A one-compartment model was used as the structural model, and individual pharmacokinetic parameters were estimated by Bayesian modeling. PYR (1.25 mg/kg of body weight) and SDX (25 mg/kg) were administered orally every 10 days for 1 year, with adjustment of the dose to body weight every 3 months. Drug concentrations were measured by high-performance liquid chromatography. A total of 101 measurements in serum were available for both drugs. Mean absorption rate constants, volumes of distribution, elimination rate constants, and half-lives were 0.915 h(-1), 4.379 liters/kg, 0.00839 h(-1), and 5.5 days for PYR and 1.659 h(-1), 0.392 liters/kg, 0.00526 h(-1), and 6.6 days for SDX, respectively. Wide interindividual variability was observed. The estimated minimum and maximum concentrations of PYR in serum differed 8- and 25-fold among patients, respectively, and those of SDX differed 4- and 5-fold, respectively. Increases in the concentration of PYR were observed for eight children, and increases in the SDX concentration were observed for seven children. Serum PYR-SDX concentrations are unpredictable even when the dose is standardized for body weight. The concentrations of the PYR-SDX combination that are most efficacious for children have not yet been established. A model such as ours, associated with long-term follow-up, is needed to study the correlation between exposure to these two drugs and clinical outcome in children.
Topics: Antiprotozoal Agents; Bayes Theorem; Body Weight; Child; Chromatography, High Pressure Liquid; Follow-Up Studies; Half-Life; Humans; Infant; Infant, Newborn; Models, Biological; Population; Pyrimethamine; Sulfadoxine; Toxoplasmosis
PubMed: 15388436
DOI: 10.1128/AAC.48.10.3794-3800.2004 -
Malaria Journal Sep 2015Sympatric existence of Plasmodium falciparum and Plasmodium vivax, and the practice of malaria treatment without microscopic confirmation suggest that the accidental...
BACKGROUND
Sympatric existence of Plasmodium falciparum and Plasmodium vivax, and the practice of malaria treatment without microscopic confirmation suggest that the accidental treatment of vivax malaria with sulfadoxine-pyrimethamine (SP) is common.
METHODS
In this study, the frequency distribution of alleles associated with SP resistance were analysed among the P. vivax infections from malariometric surveys and its association with SP treatment failure in clinical studies in Indonesia. The dhfr and dhps alleles were detected using PCR-RFLP method.
RESULTS
Analysis of 159 P. vivax isolates from malariometric surveys and 69 samples from in vivo SP efficacy study revealed various the existence of various alleles of the pvdhfr and pfdhps genes including 57L/I, 58R, 61M, and 117N/T. Allele 13L of the dhfr gene and 553G of the dhps gene were not detected in any isolates examined in both studies. In the dhfr gene, tandem repeat type-A was the major tandem repeat observed in any isolates analysed. In the dhps gene, only the 383G allele was observed. Isolates carrying double, triple and quadruple mutants of dhfr gene were found in Lampung, Purworejo, Sumba, and Papua. Although this study revealed a wide distribution of dhfr and dhps alleles among the P. vivax isolates across a broad geographic regions in Indonesia, impact on SP efficacy was not observed in Sumba.
CONCLUSION
With proper malaria diagnosis, SP may still be used as a rational anti-malarial drug either as a single prescription or in combination with artemisinin.
Topics: Adolescent; Adult; Antimalarials; Child; Child, Preschool; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Female; Gene Frequency; Humans; Indonesia; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; Pyrimethamine; Sulfadoxine; Surveys and Questionnaires; Tetrahydrofolate Dehydrogenase; Treatment Failure; Young Adult
PubMed: 26395428
DOI: 10.1186/s12936-015-0903-0 -
The Lancet. Global Health Jul 2020Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine.
METHODS
We defined treatment as random assignment to sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine before pooling individual participant-level data from 1617 HIV-uninfected pregnant women in Kenya (one trial; n=806) and Uganda (two trials; n=811). We quantified the relative effect of treatment on birthweight (primary outcome) attributed to preventing placental malaria infection (mediator). We estimated antimalarial (indirect) and non-malarial (direct) effects of IPTp on birth outcomes using causal mediation analyses, accounting for confounders. We used two-stage individual participant data meta-analyses to calculate pooled-effect sizes.
FINDINGS
Overall, birthweight was higher among neonates of women randomly assigned to sulfadoxine-pyrimethamine compared with women assigned to dihydroartemisinin-piperaquine (mean difference 69 g, 95% CI 26 to 112), despite placental malaria infection being lower in the dihydroartemisinin-piperaquine group (relative risk [RR] 0·64, 95% CI 0·39 to 1·04). Mediation analyses showed sulfadoxine-pyrimethamine conferred a greater non-malarial effect than did dihydroartemisinin-piperaquine (mean difference 87 g, 95% CI 43 to 131), whereas dihydroartemisinin-piperaquine conferred a slightly larger antimalarial effect than did sulfadoxine-pyrimethamine (8 g, -9 to 26), although more frequent dosing increased the antimalarial effect (31 g, 3 to 60).
INTERPRETATION
IPTp with sulfadoxine-pyrimethamine appears to have potent non-malarial effects on birthweight. Further research is needed to evaluate monthly dihydroartemisinin-piperaquine with sulfadoxine-pyrimethamine (or another compound with non-malarial effects) to achieve greater protection against malarial and non-malarial causes of low birthweight.
FUNDING
Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation, and Worldwide Antimalarial Resistance Network.
Topics: Adult; Antimalarials; Birth Weight; Drug Combinations; Female; Humans; Infant, Newborn; Kenya; Malaria; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine; Uganda; Young Adult
PubMed: 32562650
DOI: 10.1016/S2214-109X(20)30119-4 -
Scientific Reports Jul 2023Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in...
Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing.
Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt, Pfmdr1, Pfdhps, Pfdhfr, and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (Pfdhfr/Pfdhps: N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.
Topics: Pregnancy; Female; Humans; Kenya; Malaria, Falciparum; Antimalarials; Pyrimethamine; Sulfadoxine; Malaria; Plasmodium falciparum; Drug Resistance; Drug Combinations; High-Throughput Nucleotide Sequencing
PubMed: 37452073
DOI: 10.1038/s41598-023-38481-3 -
Pathogens and Global Health Jul 2021Malaria remains a major public health issue for pregnant women. Côte d'Ivoire has adopted a series of measures aimed at combatting this plague, and these measures...
Malaria remains a major public health issue for pregnant women. Côte d'Ivoire has adopted a series of measures aimed at combatting this plague, and these measures include administering Sulfadoxine-Pyrimethamine (SP) as an intermittent preventive treatment to pregnant women in the second and third terms.This cross-sectional study included a parturient population after informed written consent. We recruited women from the Terre Rouge maternity ward and the labor room of the Regional Medical Center of San-Pedro. Plasmodial DNA (desoxyribo nucleic acid) was extracted from Whatman filter papers with dried blood samples prepared from the venous, placental, and cord blood, utilizing Chelex 100. The extracts obtained were amplified by nested PCR.In all, 197 women were included, with an average age of 27-year-old (sd = 6.7 years old). The rates of the placental, venous and cord blood infections were 16, 2%, 15, 2% and 3, 6%, respectively. The women who took three doses of ITP were less infected at the cord (3, 2%), placental (10,6%) and venous level (13,8%). A statistically significant relationship between the number of doses and the rate of placental infection was established (p = 0.042). IPT reduces plasmodial infestation at the placental (OR = 0.4; CI = [0.2-1]), cord (OR = 0.8; CI = [0.2-3.7]) and venous (OR = 0.8; CI = [0.6-2.3]) level.In conclusion, the low frequency of placental, venous, and cord infestation in pregnant women who consistently followed a preventive treatment strategy clearly showed the efficiency of IPT against malaria during pregnancy.
Topics: Adult; Antimalarials; Cote d'Ivoire; Cross-Sectional Studies; Drug Combinations; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Parasitic; Pregnant Women; Pyrimethamine; Sulfadoxine; Young Adult
PubMed: 33769232
DOI: 10.1080/20477724.2021.1903141