Quality of antimalarials at the epicenter of antimalarial drug resistance: results from an overt and mystery client survey in Cambodia.
Ontology highlight
ABSTRACT:
SUBMITTER: Yeung S
PROVIDER: S-EPMC4455075 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The Adolescent Health Quality of Care (AHQOC) index is a tool designed to evaluate the quality of facility-based adolescent sexual and reproductive health (ASRH) services. This descriptive cross-sectional study aimed to validate the AHQOC index in 27 primary and secondary public health facilities located in a rural and an urban local government area (LGA) of Ogun State, Nigeria. To conduct the study, 12 mystery clients (MCs) were recruited and performed 144 visits to the health facilities. The MCs were young males and females who were seeking information on premarital sex, pregnancy prevention, sexually transmitted infections (STIs), and contraception. The validity, and reliability of the AHQOC index were evaluated using exploratory factor analysis, Cronbach's Alpha, and intra-class correlation coefficient tests. The Kaiser-Meyer-Olkin test result for the initial 37-item pool was 0.7169, and the final tool retained 27 items with a Cronbach's Alpha of 0.80. Two subscales of the index had Cronbach's Alpha of 0.76 and 0.85. The intra-rater consistency assessed by the intra-class correlation coefficient was 0.66 (0.10-0.92) p = 0.001 for the urban LGA and 0.72 (0.37-0.91) p = 0.001 for the rural LGA. Positive and statistically significant relationships were observed between the full scales and subscales and the validity item (MC ranking of health worker on proficiency from 1 to 10). The results of this study demonstrate that the validated AHQOC index is a valuable tool for assessing the quality of ASRH services in public health facilities.
| S-EPMC10270626 | biostudies-literature
Project description:Ensuring that artemisinin-containing antimalarials (ACAs) are of good quality is a key component of effective malaria treatment. There are concerns that a high proportion of ACAs are falsified or substandard, though estimates are rarely based on representative data. During a nationally representative survey in Tanzania, ACAs were purchased from private retail drug outlets, and the active pharmaceutical ingredient (API) was measured. All 1,737 ACAs contained the labeled artemisinin derivative, with 4.1% being outside the 85-115% artemisinin API range defined as acceptable quality. World Health Organization (WHO) prequalified drugs had 0.1 times the odds of being poor quality compared with non-prequalified ACAs for the artemisinin component. When partner components of combination therapies were also considered, 12.1% were outside the acceptable API range, and WHO prequalified ACAs had 0.04 times the odds of being poor quality. Although the prevalence of poor quality ACAs was lower than reported elsewhere, the minority of samples found to be substandard is a cause for concern. Improvements in quality could be achieved by increasing the predominance of WHO prequalified products in the market. Continued monitoring of quality standards is essential.
| S-EPMC4455080 | biostudies-other
Project description:The peroxide bond of the artemisinins inspired the development of a class of fully synthetic 1,2,4-trioxolane-based antimalarials, collectively known as the ozonides. Similar to the artemisinins, heme-mediated degradation of the ozonides generates highly reactive radical species that are thought to mediate parasite killing by damaging critical parasite biomolecules. We examined the relationship between parasite dependent degradation and antimalarial activity for two ozonides, OZ277 (arterolane) and OZ439 (artefenomel), using a combination of in vitro drug stability and pulsed-exposure activity assays. Our results showed that drug degradation is parasite stage dependent and positively correlates with parasite load. Increasing trophozoite-stage parasitemia leads to substantially higher rates of degradation for both OZ277 and OZ439, and this is associated with a reduction in in vitro antimalarial activity. Under conditions of very high parasitemia (∼90%), OZ277 and OZ439 were rapidly degraded and completely devoid of activity in trophozoite-stage parasite cultures exposed to a 3-h drug pulse. This study highlights the impact of increasing parasite load on ozonide stability and in vitro antimalarial activity and should be considered when investigating the antimalarial mode of action of the ozonide antimalarials under conditions of high parasitemia.
| S-EPMC5826100 | biostudies-literature
Project description:For an increasing number of antimalarial agents identified in high-throughput phenotypic screens, there is evidence that they target PfATP4, a putative Na+ efflux transporter on the plasma membrane of the human malaria parasite Plasmodium falciparum For several such "PfATP4-associated" compounds, it has been noted that their addition to parasitized erythrocytes results in cell swelling. Here we show that six structurally diverse PfATP4-associated compounds, including the clinical candidate KAE609 (cipargamin), induce swelling of both isolated blood-stage parasites and intact parasitized erythrocytes. The swelling of isolated parasites is dependent on the presence of Na+ in the external environment and may be attributed to the osmotic consequences of Na+ uptake. The swelling of the parasitized erythrocyte results in an increase in its osmotic fragility. Countering cell swelling by increasing the osmolarity of the extracellular medium reduces the antiplasmodial efficacy of PfATP4-associated compounds, consistent with cell swelling playing a role in the antimalarial activity of this class of compounds.
| S-EPMC5971608 | biostudies-literature
Project description:Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether prevalent drug resistance and antimalarial use has led to a concentration of drug-resistant parasites among gametocyte carriers. Although report of prior antimalarial use increased from 2008 to 2014, the prevalence of study participants presenting with microscopic gametocyte carriage declined. Gametocytemia was more common in those reporting antimalarial use within the past year, and prior antimalarial use was correlated with higher IC50s to piperaquine and mefloquine, as well as to increased pfmdr1 copy number. However, there was no association between microscopic gametocyte carriage and parasite drug resistance. Thus, we found no evidence that the infectious reservoir, marked by those carrying gametocytes, is enriched with drug-resistant parasites.
| S-EPMC6221238 | biostudies-literature
Project description:BACKGROUND: Malaria has always been a major public health problem in Yemen. Several studies in developing countries have demonstrated ineffective and poor quality drugs including antimalarials. Therefore, quality assessment of antimalarial drugs is of crucial importance. This study aimed to assess the quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine) available in Yemen and to determine whether the quality of these products was related to the level of the distribution chain at which the samples were collected or related to the manufacturers. METHODS: Four samples from each antimalarial product were collected from each of the various levels of the distribution chain. One sample was kept with the research team. Two were tested at Sana'a and Aden Drug Quality Control Laboratories. The fourth was sent to the Centre for Quality Assurance of Medicines in Potchefstroom, South Africa, for analysis. Quality indicators measured were the content of the active ingredient and dissolution rate (for tablets only) in comparison to standard specifications for these products in the relevant pharmacopoeia. RESULTS: The results identified several problems of sub-standard products within the drug distribution chain. They included high and low failures in ingredient content for chloroquine tablets and chloroquine syrup. There was some dissolution failure for chloroquine tablets, and high sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the dissolution of the pyrimethamine were found at most of the collection points. No clear relationship neither between the quality products and the level of the distribution chain, nor between locally manufactured and imported products was observed. CONCLUSION: There are sub-standard antimalarial products circulating within the drug distribution chains in the country, which will have serious implications on the reduced therapeutic effectiveness and on the development of drug resistance. This appears to be due to non-compliance with Good Manufacturing Practice guidelines by manufacturers in the production of the antimalarials.
| S-EPMC1192817 | biostudies-other
Project description:Chemotherapy plays a key role in breast cancer therapy, but drug resistance and unwanted side effects make the treatment less effective. We propose a new combination model that combines antineoplastic drugs and antimalarials for breast cancer therapy. Cytotoxic effects of two antineoplastic agents alone and in combination with several antimalarials on MCF-7 tumor cell line was evaluated. Different concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay method. The results indicate doxorubicin (DOX) and paclitaxel (PTX) alone at concentrations of their IC50 and higher are cell growth inhibitors. Mefloquine, artesunate, and chloroquine at concentrations of their IC50 demonstrate anti-cancer activity. In combination, almost all antimalarials demonstrate higher ability than DOX and PTX alone to decrease cell viability at concentrations of IC50 and lower than their IC50. The combination of chloroquine, artesunate and mefloquine with DOX and PTX was synergic (CI < 1). The combination of DOX and mefloquine after 48 h incubation demonstrated the highest cytotoxicity against MCF-7 cells, and the combination of DOX and artesunate was the most synergic. These results suggest antimalarials could act synergistically with DOX/PTX for breast cancer therapy.
| S-EPMC7761440 | biostudies-literature
Project description:Previous research has shown that clients are better able to achieve their reproductive intentions when family planning (FP) services meet their needs and they have satisfying client provider interactions. There are several areas of quality provider-client communication, including providers taking a complete reproductive history of their clients to best gauge their needs, communication around alternative FP methods and side effects captured in the method information index, and communication around sexually transmitted infections and HIV risk as it relates to FP choices. This study examines data from a clinic-based intervention in Togo that focuses on strengthening health provider counseling related to FP, including improving in these three areas of provider-client communication. A clustered sampling approach was used to select 650 FP clients from 23 intervention facilities and 235 clients from 17 control facilities in the Lomé and Kara districts of Togo. The FP clients' interactions with providers were observed and clients exit interviews were conducted in December 2021. For each communication area measured through client interviews and observations, principal components analysis and Cronbach's alpha scores were used to ensure that the individual components could be indexed. Outcomes variables based on an index of sub-questions were then created for those who had fulfilled each of the components within an index. Multivariate multilevel mixed-effects logit models accounted for clients nested within facilities and included independent variables capturing client demographic and facility variables. Multivariate results show that all three outcome variables representing the three provider-client communication areas were statistically significantly better for FP clients in intervention clinics versus control clinics (p<0.05). The results speak to the emphasis that the Togo Ministry of Health has placed on building the provider capacity to provide quality counseling and administration of FP methods and working to assist in achieving health programming goals through well-designed interventions.
| S-EPMC10249824 | biostudies-literature
Project description:Mass drug administration (MDA) to interrupt malaria transmission requires the participation of entire communities. As part of a clinical trial in western Cambodia, four villages received MDA in 2015-2016. Before approaching study communities, a collaboration was established with the local health authorities, village leaders, and village malaria workers. Formative research guided the development of engagement strategies. In each village, a team of volunteers was formed to explain MDA to their neighbors and provide support during implementation. Public mobilization events featuring drama and music were used to introduce MDA. Villages comprised groups with different levels of understanding and interests; therefore, multiple tailored engagement strategies were required. The main challenges were explaining malaria transmission, managing perceptions of drug side effects, and reaching mobile populations. It was important that local leaders took a central role in community engagement. Coverage during each round of MDA averaged 84%, which met the target for the trial.
| S-EPMC5928715 | biostudies-literature
Project description:To cope with growing resistance to current antimalarials, new drugs with novel modes of action are urgently needed. Molecules targeting protein synthesis appear to be promising candidates. We identified a compound (MMV665909) from the Medicines for Malaria Venture (MMV) Malaria Box of candidate antimalarials that could produce synergistic growth inhibition with the aminoglycoside antibiotic paromomycin, suggesting a possible action of the compound in mRNA mistranslation. This mechanism of action was substantiated with a Saccharomyces cerevisiae model using available reporters of mistranslation and other genetic tools. Mistranslation induced by MMV665909 was oxygen dependent, suggesting a role for reactive oxygen species (ROS). Overexpression of Rli1 (a ROS-sensitive, conserved FeS protein essential in mRNA translation) rescued inhibition by MMV665909, consistent with the drug's action on translation fidelity being mediated through Rli1. The MMV drug also synergized with major quinoline-derived antimalarials which can perturb amino acid availability or promote ROS stress: chloroquine, amodiaquine, and primaquine. The data collectively suggest translation fidelity as a novel target of antimalarial action and support MMV665909 as a promising drug candidate.
| S-EPMC5571370 | biostudies-literature