-
BMJ Global Health Apr 2023Coverage of antenatal iron and folic acid (IFA) supplementation and malaria chemoprophylaxis remains low in many low-income and middle-income settings. We assessed the... (Randomized Controlled Trial)
Randomized Controlled Trial
Improving coverage of antenatal iron and folic acid supplementation and malaria prophylaxis through targeted information and home deliveries in Côte d'Ivoire: a cluster randomised controlled trial.
INTRODUCTION
Coverage of antenatal iron and folic acid (IFA) supplementation and malaria chemoprophylaxis remains low in many low-income and middle-income settings. We assessed the effectiveness of personal information (INFO) sessions and personal information session plus home deliveries (INFO+DELIV) to increase coverage of IFA supplementation and intermittent preventive treatment in pregnancy (IPTp), and their effectiveness on postpartum anaemia and malaria infection.
METHODS
We included 118 clusters randomised to a control (39), INFO (39) and INFO+DELIV (40) arm, in a trial conducted between 2020 and 2021 with pregnant women (age ≥15 years) in their first or second trimester of pregnancy in Taabo, Côte d'Ivoire. We used generalised linear regression models to assess intervention impact in postpartum anaemia and malaria parasitaemia, and displayed resulting estimates as prevalence ratios.
RESULTS
Overall, 767 pregnant women were enrolled and 716 (93.3%) were followed up after delivery. Neither intervention had an impact on postpartum anaemia, with estimated adjusted prevalence ratios (aPRs) of 0.97 (95% CI 0.79 to 1.19, p=0.770) for INFO and 0.87 (95% CI 0.70 to 1.09, p=0.235) for INFO+DELIV. While INFO had no effect on malaria parasitaemia (aPR=0.95, 95% CI 0.39 to 2.31, p=0.915), INFO+DELIV reduced malaria parasitaemia by 83% (aPR=0.17, 95% CI 0.04 to 0.75, p=0.019). No improvements in antenatal care (ANC) coverage (aPR=1.05, 95% CI 0.81 to 1.36, p=0.692), IFA (aPR=2.00, 95% CI 0.89 to 4.46, p=0.093) and IPTp (aPR=1.03, 95% CI 0.87 to 1.21, p=0.728) compliance were found for INFO. INFO+DELIV increased ANC attendance (aPR=1.35, 95% CI 1.02 to 1.78, p=0.037) and compliance with IPTp (aPR=1.60, 95% CI 1.41 to 1.80, p<0.001) and IFA recommendations (aPR=7.06, 95% CI 3.68 to 13.51, p<0.001).
CONCLUSIONS
INFO+DELIV can substantially increase compliance with IFA supplementation and improve malaria prevention. However, the increases in IFA supplementation are likely insufficient to address the prevalence of often severe anaemia in this population.
TRIAL REGISTRATION NUMBER
NCT04250428.
Topics: Pregnancy; Female; Humans; Adolescent; Sulfadoxine; Pyrimethamine; Iron; Cote d'Ivoire; Drug Combinations; Malaria; Folic Acid; Anemia; Dietary Supplements
PubMed: 37076197
DOI: 10.1136/bmjgh-2022-010934 -
PloS One 2022Adequate intermittent preventive treatment (IPTp) uptake (≥3 doses) routinely delivered at antenatal clinics is effective in preventing malaria during pregnancy....
INTRODUCTION
Adequate intermittent preventive treatment (IPTp) uptake (≥3 doses) routinely delivered at antenatal clinics is effective in preventing malaria during pregnancy. Whereas, low IPTp uptake (24.0%) had been reported among pregnant women in Ebonyi State, there is paucity of studies comparing the uptake and its predictors in the urban and rural areas of Ebonyi State. We determined IPTp uptake and its predictors in the urban and rural areas of Ebonyi State.
METHODS
We conducted a cross-sectional comparative study among 864 reproductive age women selected using multistage sampling. Using a structured interviewer-administered questionnaire, we collected data on respondent's socio-demographic characteristics and IPTp uptake. Uptake was adjudged adequate if ≥3 doses were taken, otherwise inadequate. We estimated the proportion of women with adequate IPTp uptake and determined the factors associated with adequate uptake in rural and urban areas using chi square and multiple logistic regression at 5% level of significance.
RESULTS
The mean ages of respondents in the urban and rural areas were 28.5±4.6 and 27.4±5.0 years respectively. Adequate IPTp uptake was 82.5% and 60.8% in the urban and rural respectively (p<0.001). In the urban area, women whose husbands had attained ≥ secondary education (aOR:2.9; 95%CI:1.2-7.4; p = 0.02) and those who paid for sulfadoxine/pyrimethamime (aOR:0.2; 95%CI: 0.1-0.6; p = 0.01) were 2.9 times more likely and 5 times less likely to take adequate IPTp respectively compared to respondents whose husbands had attained ≤ primary education and those who had sulfadoxine/pyrimethamine free. In the rural area, women who had attended ANC <4 times (aOR:0.4; 95%CI: 0.3-0.7; p<0.001) were 2.5 times less likely to take adequate IPTp compared to women that had attended ANC ≥4 times.
CONCLUSION
Uptake of IPTp was more in the urban than rural areas of Ebonyi State. Interventions that reinforce the importance of health professionals carrying out actions aimed at pregnant women and their partners (spousal) in order to guide them on preventive actions against malaria and other diseases are recommended in Ebonyi State.
Topics: Female; Humans; Pregnancy; Young Adult; Adult; Sulfadoxine; Pregnant Women; Pregnancy Complications, Parasitic; Nigeria; Antimalarials; Cross-Sectional Studies; Prenatal Care; Malaria; Drug Combinations
PubMed: 36355851
DOI: 10.1371/journal.pone.0269305 -
AAPS PharmSciTech Oct 2016Poor aqueous solubility of drugs and the improvement thereof has always been a challenge for the pharmaceutical industry. With this, one of the focuses of the...
Poor aqueous solubility of drugs and the improvement thereof has always been a challenge for the pharmaceutical industry. With this, one of the focuses of the pharmaceutical research scientist involves investigating possible metastable forms of a given drug to be incorporated into solid dosage forms. The rationale being, the improved solubility offered by the metastable solid-state forms of drugs. Solubility remains a major challenge for formulation scientists, especially with antimicrobial agents where the emergence of resistance is directly dependent on the concentration and duration of the parasite exposed to the drug. Sulfadoxine-pyrimethamine combination therapies are still the recommended treatments for uncomplicated Plasmodium falciparum malaria. The aim of this study was to prepare an amorphous form of sulfadoxine and to investigate the stability and recrystallization behavior thereof. The amorphous form was prepared by the well-known quench cooling of the melt. The physico-chemical properties and stability of amorphous sulfadoxine were studied using hot-stage microscopy (HSM), scanning electron microscopy (SEM), x-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), as well as microcalorimetry. The recrystallization kinetics were studied isothermally by applying the Johnson-Mehl-Avrami model and non-isothermally by applying the Kissinger model. The physical stabilization of the amorphous form was investigated using physical mixtures of amorphous sulfadoxine with polyvinylpyrrolidone-25 (PVP-25). It was proved that sulfadoxine is a good glass former with relative high physical stability; however, water acts as a strong plasticizer for amorphous sulfadoxine, detrimentally affecting the stability during exposure to high moisture conditions.
Topics: Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallization; Drug Combinations; Drug Compounding; Drug Stability; Kinetics; Microscopy, Electron, Scanning; Models, Chemical; Polymers; Povidone; Powders; Pyrimethamine; Solubility; Sulfadoxine; Temperature; Water; X-Rays
PubMed: 26531745
DOI: 10.1208/s12249-015-0436-4 -
Infectious Diseases of Poverty Jul 2020Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine (SP) has been largely reported among pregnant women. However, the profile of resistance markers to SP...
BACKGROUND
Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine (SP) has been largely reported among pregnant women. However, the profile of resistance markers to SP dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) in the general population are varied and not frequently monitored. Currently, SP is used as partner drug for artemisinin combination therapy (SP-artesunate) in some sub-Saharan African countries or as a prophylactic drug in intermittent preventive treatment of malaria during pregnancy and infants and in seasonal malaria chemoprevention (SMC). Profiling of P. falciparum-resistant genotypes to SP is dynamic and critical in providing data that would be useful for malaria control programmes. This study assessed the profile of dhfr and dhps genes genotypes among individuals with malaria in Lagos, Nigeria.
METHODS
Molecular markers of SP resistance were identified by nested PCR and sequenced among malaria positive dried blood spots (DBS) that were collected from individuals attending health facilities from January 2013 to February 2014 and during community surveys from October 2010 to September 2011 across different Local Government Areas of Lagos State, Nigeria.
RESULTS
A total of 242 and 167 samples were sequenced for dhfr and dhps, respectively. Sequence analysis of dhfr showed that 95.5% (231/242), 96.3% (233/242) and 96.7% (234/242) of the samples had N51I, C59R and S108N mutant alleles, respectively. The prevalence of dhps mutation at codons A437G, A613S, S436A, A581G, I431V and K540E were 95.8% (160/167), 41.9% (70/167), 41.3% (69/167), 31.1% (52/167), 25.1% (42/167), and 1.2% (2/167) respectively. The prevalence of triple mutations (CIRNI) in dhfr was 93.8% and 44.3% for the single dhps haplotype mutation (SGKAA). Partial SP-resistance due to quadruple dhfr-dhps haplotype mutations (CIRNI-SGKAA) and octuple haplotype mutations (CIRNI-VAGKGS) with rate of 42.6% and 22.0%, respectively has been reported.
CONCLUSIONS
There was increased prevalence in dhfr triple haplotype mutations when compared with previous reports in the same environment but aligned with high prevalence in other locations in Nigeria and other countries in Africa. Also, high prevalence of dhfr and dhps mutant alleles occurred in the study areas in Lagos, Nigeria five to eight years after the introduction of artemisinin combination therapy underscores the need for continuous monitoring.
Topics: Antimalarials; Drug Combinations; Drug Resistance; Genotype; Mutation; Plasmodium falciparum; Pyrimethamine; Sulfadoxine
PubMed: 32653033
DOI: 10.1186/s40249-020-00712-4 -
Malaria Journal Feb 2021In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from...
BACKGROUND
In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. Because SP is still used for intermittent preventive treatment in pregnant women (IPTp) and seasonal malaria chemoprevention (SMCP) in Benin, the prevalence of Pfdhfr and Pfdhps SNPs in P. falciparum isolates collected in 2017 were investigated.
METHODS
This study was carried out in two sites where the transmission of P. falciparum malaria is hyper-endemic: Klouékanmey and Djougou. Blood samples were collected from 178 febrile children 6-59 months old with confirmed uncomplicated P. falciparum malaria and were genotyped for SNPs associated with SP resistance.
RESULTS
The Pfdhfr triple mutant IRN (N51I, C59R, and S108N) was the most prevalent (84.6%) haplotype and was commonly found with the Pfdhps single mutant A437G (50.5%) or with the Pfdhps double mutant S436A and A437G (33.7%). The quintuple mutant, Pfdhfr IRN/Pfdhps GE (A437G and K540E), was rarely observed (0.8%). The A581G and A613S mutant alleles were found in 2.6 and 3.9% of isolates, respectively. Six isolates (3.9%) were shown to harbour a mutation at codon I431V, recently identified in West African parasites.
CONCLUSIONS
This study showed that Pfdhfr triple IRN mutants are near fixation in this population and that the highly sulfadoxine-resistant Pfdhps alleles are not widespread in Benin. These data support the continued use of SP for chemoprevention in these study sites, which should be complemented by periodic nationwide molecular surveillance to detect emergence of resistant genotypes.
Topics: Alleles; Antimalarials; Benin; Child, Preschool; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Female; Humans; Infant; Malaria, Falciparum; Male; Plasmodium falciparum; Prevalence; Pyrimethamine; Sulfadoxine
PubMed: 33546703
DOI: 10.1186/s12936-021-03605-5 -
MalariaWorld Journal 2022Malaria in pregnancy is a significant public health concern in Nigeria. It threatens pregnant women and their unborn babies and undermines the achievement of Sustainable...
BACKGROUND
Malaria in pregnancy is a significant public health concern in Nigeria. It threatens pregnant women and their unborn babies and undermines the achievement of Sustainable Development Goal 3. The World Health Organization has recommended intermittent preventive treatment with sulfadoxine-pyrimethamine [IPTp-SP] for its control, but there are challenges to its access and uptake.
METHODS
Using the Arksey and O'Malley framework and the cascade of care model, we conducted a scoping review to investigate barriers and facilitators of IPTp-SP access and uptake, including their influence on pregnant women's health-seeking behaviour for the control of malaria in pregnancy in Nigeria. We searched seven scientific databases for papers published from 2005 to date.
RESULTS
We included a total of 31 out of 2149 articles in the review. Poor provider knowledge of the IPTp-SP protocol and lack of essential commodities for sulphadoxine-pyrimethamine administration in clinics are significant barriers to IPTp-SP use. Staff shortages and poor remuneration of health care professionals are obstacles to IPTp-SP utilisation.
CONCLUSIONS
To improve IPTp-SP access and uptake, the government should ensure a continuous supply to clinics and support the employment of additional health care professionals who should be well paid and trained on using the IPTp-SP protocol.
PubMed: 35813271
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Dec 2023Malaria molecular surveillance remains critical in detecting and tracking emerging parasite resistance to anti-malarial drugs. The current study employed molecular...
Malaria molecular surveillance remains critical in detecting and tracking emerging parasite resistance to anti-malarial drugs. The current study employed molecular techniques to determine species prevalence and characterize the genetic diversity of and molecular markers of sulfadoxine-pyrimethamine resistance in humans and wild mosquito populations in Cameroon. mosquito collections and parasitological survey were conducted in villages to determine species infection, and genomic phenotyping of anti-folate resistance was accomplished by sequencing the dihydrofolate-reductase () and dihydropteroate-synthase () genes of naturally circulating and isolates. The malaria prevalence in Elende was 73.5% with the 5-15 years age group harboring significant (27%) and (19%) infections. The polymorphism breadth of the pyrimethamine-associated marker revealed a near fixation (94%) of the triple-mutant -AI. The backbone mediating sulfadoxine resistance reveals a high frequency of the KAA alleles (20.8%). Similarly, the NKSSFI haplotype (78.4%) was predominantly detected in the asexual blood stage. In contrast, the - occured at 37.2% frequency. The combined quadruple NKSSFI_ KAA (31.9%) was the major circulating haplotype with similar frequency in humans and mosquitoes. This study highlights the increasing frequency of the parasite mostly common in asymptomatic individuals with apparent infection. Interventions directed at reducing malaria transmission such as the scaling-up of SP are favoring the emergence and spread of multiple drug-resistant alleles between the human and mosquito host systems.
Topics: Animals; Humans; Pyrimethamine; Sulfadoxine; Anopheles; Alleles; Cameroon; Antimalarials; Malaria, Falciparum; Drug Combinations; Plasmodium falciparum; Malaria; Drug Resistance; Tetrahydrofolate Dehydrogenase
PubMed: 37947766
DOI: 10.1128/aac.00588-23 -
Malaria Journal Feb 2021In Tanzania, the uptake of optimal doses (≥ 3) of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria (IPTp-SP) during pregnancy has remained...
Predictors for the uptake of optimal doses of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy in Tanzania: further analysis of the data of the 2015-2016 Tanzania demographic and health survey and malaria indicator survey.
BACKGROUND
In Tanzania, the uptake of optimal doses (≥ 3) of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria (IPTp-SP) during pregnancy has remained below the recommended target of 80%. Therefore, this study aimed to investigate the predictors for the uptake of optimal IPTp-SP among pregnant women in Tanzania.
METHODS
This study used data from the 2015-16 Tanzania demographic and health survey and malaria indicator survey (TDHS-MIS). The study had a total of 4111 women aged 15 to 49 who had live births 2 years preceding the survey. The outcome variable was uptake of three or more doses of IPTp-SP, and the independent variables were age, marital status, education level, place of residence, wealth index, occupation, geographic zone, parity, the timing of first antenatal care (ANC), number of ANC visits and type of the health facility for ANC visits. Predictors for the optimal uptake of IPTp-SP were assessed using univariate and multivariable logistic regression.
RESULTS
A total of 327 (8%) women had optimal uptake of IPTp-SP doses. Among the assessed predictors, the following were significantly associated with optimal uptake of IPTp-SP doses; education level [primary (AOR: 2.2, 95% CI 1.26-3.67); secondary or higher education (AOR: 2.1, 95% CI 1.08-4.22)], attended ANC at the first trimester (AOR: 2.4, 95% CI 1.20-4.96), attended ≥ 4 ANC visits (AOR: 1.9, 95% CI 1.34-2.83), attended government health facilities (AOR: 1.5, 95% CI 1.07-1.97) and geographic zone [Central (AOR: 5, 95% CI 2.08-11.95); Southern Highlands (AOR: 2.8, 95% CI 1.15-7.02); Southwest Highlands (AOR: 2.7, 95% CI 1.03-7.29); Lake (AOR: 3.5, 95% CI 1.51-8.14); Eastern (AOR: 1.5, 95% CI 1.88-11.07)].
CONCLUSIONS
The uptake of optimal IPTp-SP doses is still low in Tanzania. The optimal uptake of IPTp-SP was associated with attending ANC in the first trimester, attending more than four ANC visits, attending government health facility for ANC, having primary, secondary, or higher education level, and geographic zone. Therefore, there is a need for health education and behavior change interventions with an emphasis on the optimal use of IPTp-SP doses.
Topics: Adolescent; Adult; Antimalarials; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Combinations; Female; Health Facilities; Humans; Malaria, Falciparum; Middle Aged; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Prenatal Care; Pyrimethamine; Sulfadoxine; Tanzania; Young Adult
PubMed: 33549094
DOI: 10.1186/s12936-021-03616-2 -
Molecules (Basel, Switzerland) Oct 2023and sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant...
and sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (-) of the stem bark of the Cameroonian medicinal plant and its isolated compounds. The purification of - led to the isolation of a new ordered limonoid derivative, 21-hydroxybourjotinolone A (), together with 15 known compounds (-) using a repeated column chromatography. Compound was obtained in an epimeric mixture of 21-melianodiol () and 21-melianodiol (). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of and the promastigote form of (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for , amphotericin B for , and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 μg/mL, while compounds displayed IC values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 μg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant 3D7 strain but highly potent toward the multidrug-resistant Dd2 (extracts, IC 2.50 ± 0.12 to 4.78 ± 0.36 μg/mL; compounds IC 2.93 ± 0.02 to 50.97 ± 0.37 μg/mL) with selectivity indices greater than 10 (SI > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21-hydroxylbourjotinolone A () + 21-melianodiol () + 21-melianodiol ()] exhibited moderate activity against and This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.
Topics: Humans; Antimalarials; Limonins; Plant Extracts; Sulfadoxine; Plant Bark; Antiprotozoal Agents; Chloroquine; Malaria, Falciparum; Meliaceae; Plasmodium falciparum
PubMed: 37894704
DOI: 10.3390/molecules28207227 -
The Lancet. Infectious Diseases Jan 2020
Topics: Antimalarials; Drug Combinations; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Insecticide-Treated Bednets; Malaria; Pregnancy; Pyrimethamine; Sulfadoxine; Treatment Refusal
PubMed: 31876483
DOI: 10.1016/S1473-3099(19)30711-X