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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 -
Malaria Journal Aug 2020Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern...
Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India.
BACKGROUND
Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015-2016 after 3-4 years of ASP use, are reported.
METHODS
Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16-185, pfdhps 436-632 and K13 407-689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism.
RESULTS
Sulfadoxine-pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively.
CONCLUSION
The frequency of P. falciparum with reduced susceptibility to sulfadoxine-pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.
Topics: Adolescent; Adult; Aged; Antimalarials; Artesunate; Child; Child, Preschool; Drug Combinations; Drug Resistance; Humans; India; Infant; Malaria, Falciparum; Middle Aged; Mutation; Plasmodium falciparum; Protozoan Proteins; Pyrimethamine; Sulfadoxine; Young Adult
PubMed: 32795288
DOI: 10.1186/s12936-020-03274-w -
Microbiology Spectrum Oct 2022Sulfadoxine-pyrimethamine (SP) resistance impairs the efficacy of antimalarial drugs. Monitoring molecular markers in exported malaria infections provides an efficient...
Molecular Determinants of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from Central Africa between 2016 and 2021: Wide Geographic Spread of Highly Mutated and Alleles.
Sulfadoxine-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 and of 237 Plasmodium falciparum infections imported from central Africa between 2016 and 2021 were detected. The spatial and temporal distributions of and mutations were analyzed. A high prevalence of single-nucleotide polymorphisms (SNPs) (~92.34% to 99.10%) and a high frequency of the triple mutation haplotype were observed. Cameroon, Equatorial Guinea, and Gabon showed a higher frequency (~96.61% to 100.00%) of than other countries (~71.11% to 88.10%). The prevalence of C59R and increased while that of other SNPs or haplotypes did not fluctuate greatly from 2016 to 2021. Large proportions of SNPs (A437G and K540E) were demonstrated. The SNP distribution of 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 - 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 - allele (-K) was seen in 5.00% of the samples. We demonstrated the wide geographic spread and increasing trends in highly SP-resistant genes and varying spatial patterns of mutants across countries in central Africa. The high prevalences of partially resistant, fully resistant, and superresistant combinations observed here indicated impaired SP efficacy. Increased molecular surveillance is required to monitor the changing status of the and genes. 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 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 I431V as well as the high prevalence of "partially resistant," "fully resistant," and "superresistant" - 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.
Topics: Humans; Africa, Central; Alleles; Antimalarials; Drug Resistance; Malaria, Falciparum; Mutation; Plasmodium falciparum; Protozoan Proteins
PubMed: 36121226
DOI: 10.1128/spectrum.02005-22 -
Iranian Journal of Parasitology 2021One of the main obstacles to malaria control in the world has been the emergence of resistance in to chloroquine and other anti-malarial drugs. This study aimed to... (Review)
Review
BACKGROUND
One of the main obstacles to malaria control in the world has been the emergence of resistance in to chloroquine and other anti-malarial drugs. This study aimed to review studies in Iran on resistance in and to drugs, and to reveal the mechanisms and molecular markers of resistance of these two species.
METHODS
The databases of PubMed, Scopus, Google Scholar, Magiran, and reputable Iranian journals were searched to find published studies on the resistance in and to antimalarial drugs in Iran.
RESULTS
There is a significant relationship between resistance to chloroquine in and the emergence of K76T mutation in the chloroquine-resistance transporter gene in Iran. Resistance to sulfadoxine-pyrimethamine (SP) in is also significantly associated with the development of mutations in the dihydrofolate reductase and dihydropteroate synthase genes. Resistance to chloroquine in has not been reported in Iran and it is used as a first-line treatment for malaria.
CONCLUSION
has become resistant to chloroquine in different regions of Iran and is not currently used to treat malaria Besides, cases have emerged of resistance to SP in different parts of southern Iran, and SP is not administered alone for treating .
PubMed: 34557232
DOI: 10.18502/ijpa.v16i2.6265 -
The American Journal of Tropical... Mar 2022As the malaria elimination target draws closer for India, it must be ensured that the country's policies, strategies, and tools remain effective. Artemisinin-based...
As the malaria elimination target draws closer for India, it must be ensured that the country's policies, strategies, and tools remain effective. Artemisinin-based combination therapies are the mainstay of Plasmodium falciparum malaria management. India has a differential standard therapy for uncomplicated falciparum malaria in the form of artemether-lumefantrine in its northeastern states and artesunate + sulfadoxine-pyrimethamine in the rest of the country. The clinical failure of artesunate + sulfadoxine-pyrimethamine in the northeast regions were attributed primarily to parasite resistance resulting from mutations in the enzymes dihydropteroate synthase and dihydrofolate reductase. Artemether-lumefantrine was therefore substituted for artesunate + sulfadoxine-pyrimethamine in the region. The change has been a success, as evidenced by the therapeutic efficacy studies conducted at regular intervals in India. However, studies suggest that resistance may be emerging toward sulfadoxine-pyrimethamine in multiple parts of the nation. Hence, there is a possibility that the artesunate + sulfadoxine-pyrimethamine combination may be acting in part as a monotherapy, and this makes the longevity of the artesunate + sulfadoxine-pyrimethamine drug combination therapy uncertain. The increasing presence of drug-resistant mutants in P. falciparum dhps and dhfr genes suggests the need for a policy switch for uncomplicated P. falciparum malaria from artesunate + sulfadoxine-pyrimethamine to artemether-lumefantrine.
PubMed: 35292598
DOI: 10.4269/ajtmh.21-1095 -
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 -
Indian Journal of Public Health 2023Seasonal malaria chemoprevention (SMC) is an important public health intervention that is being used to reduce the burden of malaria in sub-Saharan Africa. (Review)
Review
BACKGROUND
Seasonal malaria chemoprevention (SMC) is an important public health intervention that is being used to reduce the burden of malaria in sub-Saharan Africa.
OBJECTIVES
This study aimed to evaluate the implementation of SMC and pharmacovigilance practices in under-five children in Kebbi State, Nigeria.
MATERIALS AND METHODS
The methodology involved a comprehensive review of tools for managing SMC commodities, training data collectors, and fieldwork to evaluate all local government area (LGA) stores, the central medical store (CMS), and selected health facilities based on the sample size determined. Data were collected using SurveyCTO software and analyzed using MS Excel. Twenty-one data reviewers visited the CMS, 21 LGA stores, and 315 health facilities.
RESULTS
Our study uncovered significant inaccuracies in documentation, which led to many commodities needing to be more effectively accounted for regarding sources. Data triangulation showed inconsistencies between tools and physical counts that do not match the quantities on inventory control cards. Most primary health-care (PHC) staff in charge of SMC have been formally trained in pharmacovigilance. About 75% (237) of PHCs referred cases of adverse drug reactions (ADRs) to a secondary health-care facility, while 14% (45) treated the symptoms of the ADR with another drug, and 7% (21) took no action, and the reaction resolved on its own.
CONCLUSIONS
This study provides insight into the challenges and opportunities for improving the implementation of SMC and pharmacovigilance practices in Kebbi State, Nigeria, and has important implications for other settings with similar challenges.
Topics: Child, Preschool; Humans; Infant; Antimalarials; Chemoprevention; India; Malaria; Nigeria; Pharmacovigilance; Seasons
PubMed: 37929374
DOI: 10.4103/ijph.ijph_577_23 -
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