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International Journal of Antimicrobial... Mar 2024India is on track to eliminate malaria by 2030 but emerging resistance to first-line antimalarials is a recognised threat. Two instances of rapid development, spread,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
India is on track to eliminate malaria by 2030 but emerging resistance to first-line antimalarials is a recognised threat. Two instances of rapid development, spread, and natural selection of drug-resistant mutant parasites in India (chloroquine across the country and artesunate + sulfadoxine-pyrimethamine [AS+SP] in the northeastern states) translated into drug policy changes for Plasmodium falciparum malaria in 2010 and 2013, respectively. Considering these rapid changes in the SP drug resistance-conferring mutation profile of P. falciparum, there is a need to systematically monitor the validated mutations in Pfdhfr and Pfdhps genes across India alongside AS+SP therapeutic efficacy studies. There has been no robust, systematic countrywide surveillance reported for these parameters in India, hence the current study was undertaken.
METHODS
Studies that reported data on WHO-validated SP resistance markers in P. falciparum across India from 2008 to January 2023 were included. Five major databases, PubMed, Web of Science, Scopus, Embase, and Google Scholar, were exhaustively searched. Individual and pooled prevalence estimates of mutations were obtained through random- and fixed-effect models. Data were depicted using forest plots created with a 95% confidence interval. The study is registered with PROSPERO (CRD42021236012).
RESULTS
A total of 37 publications, and 533 Pfdhfr and 134 Pfdhps National Centre of Biotechnology Information (NCBI) DNA sequences were included from >4000 samples. The study included information from 80 districts, 21 states and 3 union territories (UTs) from India. The two PfDHFR mutations, C59R (62%) and S108N (74%), were the most prevalent mutations (pooled estimates 61% and 71%, respectively) and appeared to be stabilised/fixed. Although rarest overall, the prevalence of I164L was observed to be as high as 32%. The PfDHFR double mutants were the most prevalent overall (51%; pooled 42%). The prevalence of triple and quadruple mutations was 6% and 5%, respectively, and is an immediate concern for some states. The most prevalent PfDHPS mutation was A437G (39%), followed by K540E (25%) and A581G (12%). There was a low overall prevalence of PfDHFR/PfDHPS quintuple and sextuple mutations but surveillance for these mutations is critical for some areas.
CONCLUSION
The analyses span the two critical policy changes, highlight the areas of concern, and guide policymakers in strategising and refining the anti-malaria drug policy for malaria elimination. The results of the analyses also highlight the SP-resistance hot spots, critical gaps and challenges, and indicate that focal and local malaria genetic surveillance (including drug-resistance markers) is needed until malaria is successfully eliminated.
Topics: Humans; Plasmodium falciparum; Pyrimethamine; Malaria, Falciparum; Antimalarials; India; Artesunate; Drug Combinations; Sulfadoxine
PubMed: 38154659
DOI: 10.1016/j.ijantimicag.2023.107071 -
Malaria Journal Nov 2023The emergence of resistance to artemisinin derivatives in Southeast Asia constitutes a serious threat for other malaria endemic areas, particularly in Côte d'Ivoire. To...
BACKGROUND
The emergence of resistance to artemisinin derivatives in Southeast Asia constitutes a serious threat for other malaria endemic areas, particularly in Côte d'Ivoire. To delay this resistance, the application of the control measures recommended by the National Malaria Control Programme (NMCP) for a correct management, in the private pharmacies, is a necessity. The purpose of this study was, therefore, to assess the level of knowledge and practices of private pharmacy auxiliary in Abidjan about the management of malaria.
METHODS
A descriptive cross-sectional study was conducted from April to November 2015. It included auxiliaries of private pharmacies in Abidjan. Data collection material was a structured an open pretested questionnaire. Data analysis was carried out using Package for Social Science (SPSS) software version 21.1. Chi square test was used to compare proportions for a significance threshold of 0.05 for the p value.
RESULTS
A total, 447 auxiliaries from 163 private pharmacies were interviewed. It was noted that the auxiliaries had a good knowledge of clinical signs of uncomplicated malaria (99.1%), biological examinations (54.6% for the thick film and 40.7% for rapid diagnostic tests (RDTs) and anti-malarial drugs (99.3% for artemether + lumefantrine, AL). The strategies of vector control (long-lasting insecticide-treated mosquito nets (LLITNs, Repellent ointments, cleaning gutters, elimination of larvae breeding site and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) in pregnant women were also known by the auxiliaries, respectively 99.8% and 77.4%. However, the malaria pathogen (25.1%) and the NMCP recommendations (e.g. use of AL or AS + AQ as first-line treatment for uncomplicated malaria and IPTp-SP in pregnant women) were not well known by the auxiliaries (28.2% and 26.9% for uncomplicated and severe malaria). Concerning the practices of the auxiliaries, 91.1% offered anti-malarial drugs to patients without a prescription and 47.3% mentioned incorrect dosages. The combination artemether + lumefantrine was the most recommended (91.3%). The delivery of anti-malarial drugs was rarely accompanied by advice on malaria prevention, neither was it carried out on the result of an RDT.
CONCLUSION
The epidemiology and the NMCP recommendations for the diagnostic and therapeutic management of malaria, are not well known to auxiliaries, which may have implications for their practices. These results show the need to sensitize and train private pharmacy auxiliaries, and also to involve them in NMCP activities.
Topics: Humans; Female; Pregnancy; Antimalarials; Pharmacies; Cote d'Ivoire; Cross-Sectional Studies; Malaria; Drug Combinations; Surveys and Questionnaires; Pharmacy; Lumefantrine; Artemether
PubMed: 37919734
DOI: 10.1186/s12936-023-04751-8 -
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 -
Acta Crystallographica. Section D,... Aug 2023Candida auris has emerged as a global health problem with a dramatic spread by nosocomial transmission and a high mortality rate. Antifungal therapy for C. auris...
Candida auris has emerged as a global health problem with a dramatic spread by nosocomial transmission and a high mortality rate. Antifungal therapy for C. auris infections is currently limited due to widespread resistance to fluconazole and amphotericin B and increasing resistance to the front-line drug echinocandin. Therefore, new treatments are urgently required to combat this pathogen. Dihydrofolate reductase (DHFR) has been validated as a potential drug target for Candida species, although no structure of the C. auris enzyme (CauDHFR) has been reported. Here, crystal structures of CauDHFR are reported as an apoenzyme, as a holoenzyme and in two ternary complexes with pyrimethamine and cycloguanil, which are common antifolates, at near-atomic resolution. Preliminary biochemical and biophysical assays and antifungal susceptibility testing with a variety of classical antifolates were also performed, highlighting the enzyme-inhibition rates and the inhibition of yeast growth. These structural and functional data might provide the basis for a novel drug-discovery campaign against this global threat.
Topics: Humans; Antifungal Agents; Candida auris; Tetrahydrofolate Dehydrogenase; Folic Acid Antagonists; Microbial Sensitivity Tests; Candidiasis, Invasive; Saccharomyces cerevisiae
PubMed: 37428844
DOI: 10.1107/S2059798323004709 -
PLoS Neglected Tropical Diseases Sep 2023We evaluate the drug treatment for pregnant women with acute toxoplasmosis to reduce the risk of congenital infection, side effects (prenatal and postnatal treatment in...
BACKGROUND
We evaluate the drug treatment for pregnant women with acute toxoplasmosis to reduce the risk of congenital infection, side effects (prenatal and postnatal treatment in children) and the hazard of discontinuing the infant's medication.
METHODS
We conducted a prospective cohort study to assess the risks of congenital toxoplasmosis among children born to acutely infected women with and without treatment. We examined the relationship between "exposed" and "infected children", "number of infant neutrophils", "prenatal" and "postnatal treatment". Factor analysis of mixed data (FAMD) was used to analyze the data. All children started treatment at the hospital.
FINDINGS
Between 2017 and 2021, 233 pregnant women were evaluated at the University Hospital of Maringá; ninety-four met criteria for acute gestational toxoplasmosis. We followed up 61 children; eleven (18%) had the infection confirmed and 50 (82%) were free of toxoplasmosis (exposed). Children born to untreated mothers have 6.5-times higher risk of being infected; the transmission rate among untreated mothers was 50% versus 8.3% among treated ones. Three decreasing values of immunoglobulin G were a security parameter for stopping the child's medication in the exposed group (50/61). Neutropenia was the leading side effect among children and the infected had a 2.7 times higher risk. There was no correlation between maternal use of pyrimethamine and children's neutropenia.
INTERPRETATION
The follow-up of women with acute T. gondii infection and their children, through a multidisciplinary team, availability of anti-T. gondii serology and pre- and post-natal treatments reduced the risk of toxoplasmosis transmission.
Topics: Infant; Humans; Female; Pregnancy; Child; Cohort Studies; Pregnancy Complications, Infectious; Prospective Studies; Brazil; Toxoplasmosis; Toxoplasmosis, Congenital; Neutropenia; Toxoplasma; Pregnancy Complications, Parasitic
PubMed: 37773943
DOI: 10.1371/journal.pntd.0011544 -
International Journal of Infectious... Oct 2023Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We...
Fetal growth and birth weight are independently reduced by malaria infection and curable sexually transmitted and reproductive tract infections in Kenya, Tanzania, and Malawi: A pregnancy cohort study.
OBJECTIVES
Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi.
METHODS
This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine vs dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis at enrollment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression.
RESULTS
In total, 1435 pregnant women had fetal/birth weight assessed 3950 times. Compared to women without malaria or STIs/RTIs (n = 399), malaria-only (n = 267), STIs/RTIs only (n = 410) or both (n = 353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% confidence interval]: malaria = -0.18 [-0.31,-0.04], P = 0.01; STIs/RTIs = -0.14 [-0.26,-0.03], P = 0.01; both = -0.20 [-0.33,-0.07], P = 0.003). Paucigravidae experienced the greatest impact.
CONCLUSION
Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs.
Topics: Female; Pregnancy; Humans; Birth Weight; Reproductive Tract Infections; Cohort Studies; Kenya; Fetal Weight; Malawi; Tanzania; Sexually Transmitted Diseases; Malaria; Pregnancy Outcome; Fetal Development
PubMed: 37516425
DOI: 10.1016/j.ijid.2023.07.012 -
Journal of the Royal Society, Interface Jan 2024The emergence and spread of drug-resistant parasites have hindered efforts to eliminate malaria. Monitoring the spread of drug resistance is vital, as drug resistance...
The emergence and spread of drug-resistant parasites have hindered efforts to eliminate malaria. Monitoring the spread of drug resistance is vital, as drug resistance can lead to widespread treatment failure. We develop a Bayesian model to produce spatio-temporal maps that depict the spread of drug resistance, and apply our methods for the antimalarial sulfadoxine-pyrimethamine. We infer from genetic count data the prevalences over space and time of various malaria parasite haplotypes associated with drug resistance. Previous work has focused on inferring the prevalence of individual molecular markers. In reality, combinations of mutations at multiple markers confer varying degrees of drug resistance to the parasite, indicating that multiple markers should be modelled together. However, the reporting of genetic count data is often inconsistent as some studies report haplotype counts, whereas some studies report mutation counts of individual markers separately. In response, we introduce a latent multinomial Gaussian process model to handle partially reported spatio-temporal count data. As drug-resistant mutations are often used as a proxy for treatment efficacy, point estimates from our spatio-temporal maps can help inform antimalarial drug policies, whereas the uncertainties from our maps can help with optimizing sampling strategies for future monitoring of drug resistance.
Topics: Humans; Antimalarials; Bayes Theorem; Malaria, Falciparum; Malaria; Plasmodium falciparum; Mutation; Biomarkers; Protozoan Proteins
PubMed: 38228183
DOI: 10.1098/rsif.2023.0570 -
Pharmaceuticals (Basel, Switzerland) Nov 2023Nowadays, interest in the use of nanotechnology for medical purposes is increasing. The current experimental investigation is planned for the green synthesis,...
BACKGROUND
Nowadays, interest in the use of nanotechnology for medical purposes is increasing. The current experimental investigation is planned for the green synthesis, characterization, and efficacy of copper nanoparticles (CLN) against chronic infection.
METHODS
Green synthesis of CNP was performed using the extract via the precipitation method. The effects of CNP on tachyzoites, infectivity rate, parasites inside THP-1 cells, nitric oxide (NO) triggering, iNOS, and IFN-γ expression genes were evaluated. Following toxoplasmosis in BALB/c mice via the ME49 strain, mice received CNP at 5 and 10 mg/kg/day alone and combined with pyrimethamine (PYM) at 5 mg/kg for two weeks. CNP's in vivo effects were evaluated by analyzing the load and size of cysts, oxidant/antioxidant enzymes, and bradyzoite surface antigen 1 (BAG1) expression gene levels.
RESULTS
CNP displayed a circular shape ranging from 10 to 85 nm. The IC50 value of CNP and PYM against tachyzoites was 37.2 and 25.7 µg/mL, respectively, whereas the CC50 value of CNP and pyrimethamine against THP-1 cells was 491.4 μg/mL and 269.5 μg/mL, respectively. The rate of infectivity and parasite load among THP-1 cells exposed to CNP was obviously reduced ( < 0.05). CNP at the doses of 5 and 10 mg/kg predominantly along with PYM evidently ( < 0.05) reduced the number and size of the cysts in the infected mice. The levels of NO, iNOS, and IFN-γ genes were remarkably ( < 0.001) boosted compared with the cells without treatment. CNP at the doses of 10 and 20 mg/kg drastically ( < 0.05) reduced the oxidative stress markers in the infected mice, whereas CNP significantly elevated the level of antioxidant factors. CNP also revealed no toxicity in the liver and kidney at the tested doses in healthy mice.
CONCLUSIONS
Our experimental study reported the beneficial effects of CNP principally along with existing chemical drugs against latent toxoplasmosis in mice, whereas the possible action mechanisms of CNP are controlling oxidative stress, refining antioxidant enzymes, and increasing the production of immunomodulatory cytokines with no toxicity to the function of vital organs. But, additional trials are required to confirm these results, as well as to clarify the accurate mechanisms and their toxicity.
PubMed: 38004439
DOI: 10.3390/ph16111574 -
The Journal of Maternal-fetal &... Dec 2023Therapeutic regimens for the treatment of toxoplasmosis are not standardized. Treatment strategy mainly at the end of the second and the beginning of the third...
Comparison of adverse reactions of spiramycin versus pyrimethamine/sulfadiazine treatment of toxoplasmosis in pregnancy: is spiramycin really the drug of choice for unproven infection of the fetus?
BACKGROUND
Therapeutic regimens for the treatment of toxoplasmosis are not standardized. Treatment strategy mainly at the end of the second and the beginning of the third trimester, especially in cases of negative prenatal diagnosis, is the least uniform. In some situations, the choice of treatment may be ambiguous, and adverse drug reactions of the therapy should be taken into consideration.
METHODS
Adverse drug reactions of anti-toxoplasma therapy with spiramycin ( = 77) versus pyrimethamine/sulfadiazine ( = 35) were compared in 112 pregnant women.
RESULTS
Up to 36.6% of women reported adverse reactions to the treatment overall ( = 41). Out of those 38.9% ( = 30) were treated with spiramycin and 31.4% ( = 11) with pyrimethamine/sulfadiazine. Toxic allergic reactions were the only indication for discontinuation of treatment in 8.9% of patients ( = 10), where 9.1% ( = 7) were reported in spiramycin and 8.6% ( = 3) in pyrimethamine/sulfadiazine cohort. Neurotoxic complications (acral paraesthesia) were significantly more frequent during the therapy with spiramycine in 19.5% ( = 15) compared to no cases in pyrimethamine/sulfadiazine group ( = .003). Other adverse drug reactions, such as gastrointestinal discomfort, nephrotoxicity, vaginal discomfort were reported, but the differences between the cohorts were not significant.
CONCLUSIONS
The superiority of one of the therapeutic regimens was not statistically demonstrated, since the differences in overall toxicity or incidence of toxic allergic reactions between the cohorts were not confirmed ( = .53 and = 1.00, respectively). However, although the isolated neurotoxicity of spiramycin was the only significant adverse reaction demonstrated in this study, pyrimethamine/sulfadiazine therapy should be preferred, because it is known to be more effective and with limited adverse reactions.
Topics: Female; Humans; Pregnancy; Spiramycin; Pyrimethamine; Sulfadiazine; Toxoplasmosis; Drug Therapy, Combination; Fetus; Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Toxoplasmosis, Congenital
PubMed: 37217458
DOI: 10.1080/14767058.2023.2215377 -
Global Health Action Dec 2023Malaria during pregnancy is a major global health concern, with approximately 10,000 pregnant women dying from malaria-related anaemia each year. The World Health...
Malaria during pregnancy is a major global health concern, with approximately 10,000 pregnant women dying from malaria-related anaemia each year. The World Health Organization has suggested intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) to avert malaria infection in pregnant women in malaria-endemic areas, but this intermittent preventive (IP) treatment is at risk of becoming ineffective due to parasite resistance and the contraindication in HIV-infected women. This paper argues that alternative IP treatments such as dihydroartemisinin-piperaquine (DP) should be explored, alongside the urgent need to investigate antimalarial cycling strategies. Additionally, the cost-effectiveness of IPTp-DP should be evaluated, as well as potential barriers to IP treatment such as medication stockouts, late attendance at antenatal clinics, lack of autonomy and freedom among women, and lack of knowledge about malaria prevention. Health education focusing on malaria prevention should be incorporated into routine antenatal care programmes to improve patient compliance. A comprehensive approach that includes the administration of IPTp-DP alone along with other measures such as insecticide-treated nets and medical education is the key to addressing the devastating effects of malaria infection in pregnant women.
Topics: Female; Pregnancy; Humans; Pregnant Women; Cost-Benefit Analysis; Antimalarials; Malaria
PubMed: 37459385
DOI: 10.1080/16549716.2023.2231257