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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Drug resistance emerges when drug use creates an environment for the pathogen that favors the selection of resistance. Similarly, drug resistance can be reversed when we create environments in which such resistance loses its selective advantage. The example of chloroquine use in the central African nation of Malawi is illustrative. Owing to heavy chloroquine use, the prevalence of the resistant PfCRT genotype in P. falciparum reached 85% in 1992. In 1993, chloroquine was removed from the market in Malawi because of its limited efficacy. After chloroquine was withdrawn, chloroquine-resistant parasites then lost their selective advantage over sensitive strains and a decline in resistance ensued. By 2000, the prevalence of the resistant genotype was only 13%. These promising results have since been mirrored in a number of other African countries from which chloroquine was withdrawn between 1998 and 2008. Figure 9.23 highlights one such example.
Phytonanotechnology
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Tafadzwa J. Chiome, Asha Srinivasan
With still a lot of work being done in cancer research, co-delivery has shown to be a viable option when it comes to improving the efficiency of cancer treatment by using nanocarriers for the dual loading of both phytochemicals and other anti-tumor agents. Such a delivery has shown to be efficient at: (i) improving drug solubility; (ii) increasing bioavailability; (iii) minimizing chances of drug resistance development; (iv) delaying cellular adaptation; (v) inducing simultaneous therapeutic effect; (vi) delivery of optimum dosage; and (vii) reduced systemic cytotoxicity. Some studies have been done on several phytochemicals in conjunction with anti-cancer drugs used as first line treatment and some of the studies are listed in Table 13.5.
Respiratory Infections
Published in Miriam Orcutt, Clare Shortall, Sarah Walpole, Aula Abbara, Sylvia Garry, Rita Issa, Alimuddin Zumla, Ibrahim Abubakar, Handbook of Refugee Health, 2021
The WHO Stop TB strategy comprises six components: political commitment and sustained financing, case detection through quality-assured bacteriology, standardised short-course chemotherapy with supervision and patient support, an effective drug supply and management system, monitoring and evaluation system and impact measurement. Human immunodeficiency virus and TB can coexist, requiring specialist treatment (due to drug interactions and risk of immune reconstitution inflammatory syndrome), and malnutrition can be seen among displaced persons. Untreated, 50% of HIV-negative patients with active TB are dead in 5 years, 25% will self-cure, and 25% will remain chronically unwell with potentially infectious TB. Infection with TB may be primary or due to reactivation; risk factors for reactivation include immunosuppression, HIV, medication, dialysis, age and diabetes. Risk factors for drug resistance include prior non-adherence, prison, HIV and contact with a known drug-resistant case.
Intratumoral Pi deprivation benefits chemoembolization therapy via increased accumulation of intracellular doxorubicin
Published in Drug Delivery, 2022
Yang-Feng Lv, Zhi-Qiang Deng, Qiu-Chen Bi, Jian-Jun Tang, Hong Chen, Chuan-Sheng Xie, Qing-Rong Liang, Yu-Hua Xu, Rong-Guang Luo, Qun Tang
Drug resistance is a complex phenomenon that can result from numerous mechanisms. Elevated efflux of anticancer agents by ATP-dependent pumps decreased intracellular drug accumulation, which has been the major reason for resistance of tumors, including HCC, to chemotherapy (Lockhart et al., 2003; Marin et al., 2009; Bar-Zeev et al., 2017; Marin et al., 2020). The resistance caused by abnormally high rates of drug efflux could be either intrinsic or acquired after drug administration. Those pumps responsible for drug efflux are transmembrane transporters, primarily from the ATP binding cassette (ABC) transporter superfamily, such as P-glycoprotein (P-gp; ABCB1; MDR1), breast cancer resistance protein (BCRP; ABCG2), and multidrug resistance-associated protein 1 (MRP1; ABCC1). Specifically, in the case of HCC, all three of these proteins are indicative of HCC progression, and inhibition of their expression contributes to better chemotherapy (Huang et al., 1992; Soini et al., 1996; Nies et al., 2001; Vander Borght et al., 2008; Sukowati et al., 2012; Huang et al., 2013). Targeting these transporters has been proposed for decades but is still far from being applied to the bedside.
Rational use of antibiotics and covariates of clinical outcomes in patients admitted to intensive care units of a tertiary hospital in Kenya
Published in Hospital Practice, 2022
Babra Ligogo Murila, David Gitonga Nyamu, Rosaline N. Kinuthia, Peter Mbugua Njogu
Due to the ever-present danger of drug resistance and a dearth of new antimicrobial drug development, rational use of antibiotics is a paramount good clinical practice to counter antimicrobial resistance and improve the quality of care of patients with infections by maximizing clinical outcomes while minimizing toxicity. In this study, antibiotics use had relatively high rationality on three of the five parameters assessed, namely route of administration (99.4%), dosing (76.7%) and frequency (69.5%). The high prevalence of irrational use of antibiotics was contributed largely by the incorrect choice (51%) and wrong duration (32.3%) of use of antibiotics, especially in surgical prophylaxis. Intubation and comorbidities were significant correlates of poor outcomes of therapy. Therefore, intensification of management in critical care units should be directed toward intubated patients with comorbidities.
Pharmacotherapy for artemisinin-resistant malaria
Published in Expert Opinion on Pharmacotherapy, 2021
Erik Koehne, Ayola Akim Adegnika, Jana Held, Andrea Kreidenweiss
Antimicrobial drug resistance is usually understood as the occurrence of bacteria, viruses, pathogens, etc. that evade killing or attenuation by a chemotherapeutic drug and continue to survive and propagate in the infected individual, maintaining the presence of the potential disease (based on the assumption of adequate dosing, pharmacokinetics, initial parasite biomass, and accounting for reinfection). The first observations of artemisinin resistance were made in 2008 in Cambodia [13,14] when the time to P. falciparum clearance following seven days artesunate monotherapy was prolonged beyond three days and some malaria patients were still parasitemic on day 28 follow-up, although most patients were cured. The WHO defines clinical artemisinin resistance as ‘delayed parasite clearance following treatment with an artemisinin-based monotherapy or with an artemisinin-based combination therapy’ [8]. This is also labeled as ‘artemisinin partial resistance’ and is suspected when 10% (or more) of malaria patients present with a parasitemia at day three or have a parasite clearance half-life beyond five hours. However, this clinical phenotype does not necessarily lead to a treatment failure commonly assessed 28 or 42 days after treatment start (timing depends on the half-life of the ACT partner drug). A failure following ACT treatment rather occurs because of an underlying resistance to the ACT partner drug that may or may not be accompanied by a partial artemisinin resistance event in the circulating P. falciparum strains [15].