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Case Reports in Infectious Diseases 2023Babesiosis is a tick-borne condition that causes hemolytic anemia and manifests with flu-like symptoms such as fevers, chills, fatigue, and anorexia. Very few case...
Babesiosis is a tick-borne condition that causes hemolytic anemia and manifests with flu-like symptoms such as fevers, chills, fatigue, and anorexia. Very few case reports have documented babesiosis infection associated with a false-positive HIV test. In this case report, we add to the current literature by describing a patient admitted for treatment of babesiosis who had a preliminary positive HIV test on admission and a negative repeat HIV test after one week of treatment for babesiosis. A 60-year-old male with a past medical history of high cholesterol presented to the Emergency Department after having abnormal laboratory tests with his primary care doctor. He reported fever, fatigue, anorexia, and worsening jaundice for three weeks. He was hypotensive and febrile on admission. A blood smear showed Babesia species with 1-2% infected red blood cells. He was admitted to the intensive care unit and received treatment with plasmapheresis, atovaquone, and antibiotics. The fourth-generation HIV 1/2 antigen/antibody test was initially positive but after treatment, HIV testing was negative. A misdiagnosis of HIV can greatly impact a patient's quality of life as antiretroviral therapy has multiple deleterious side effects. Clinicians must consider further evaluation of patients with acute babesiosis who also test positive for HIV.
PubMed: 37528903
DOI: 10.1155/2023/6271710 -
Journal of Cellular and Molecular... Oct 2023The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by...
The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.
PubMed: 37724615
DOI: 10.1111/jcmm.17940 -
Deutsche Medizinische Wochenschrift... Apr 2024A 42-year-old female presented with a two-day history of vomiting, diarrhea, fever and chills. Two weeks before she had returned to Germany from a Safari in Tanzania....
HISTORY
A 42-year-old female presented with a two-day history of vomiting, diarrhea, fever and chills. Two weeks before she had returned to Germany from a Safari in Tanzania. She had disregarded the recommendation to take antimalarial chemoprophylaxis.
CLINICAL FINDINGS AND DIAGNOSIS
The thin blood film showed -parasitized erythrocytes, and malaria was diagnosed. The full blood count showed thrombocytopenia and ultrasound imaging revealed splenomegaly. Initially the criteria for complicated malaria were not fulfilled.
THERAPY AND COURSE
We started oral therapy with atovaquone/proguanil. The patient vomited the tablets twice. Therefore therapy was switched to intravenous artesunate. Subsequently, parasitemia dropped from 2.8 to 1.0 % within 22 hours. After 3 days of artesunate i. v., treatment could then be completed with oral atovaquone/proguanil, and the symptoms resolved.
CONCLUSIONS
Patients with malaria and persistent vomiting should be treated intravenously and monitored closely, as severe gastrointestinal symptoms may reflect impending organ failure. We therefore propose including persistent vomiting in the list of criteria for complicated malaria.
Topics: Female; Humans; Adult; Proguanil; Atovaquone; Artesunate; Antimalarials; Malaria; Malaria, Falciparum; Drug Combinations; Vomiting
PubMed: 38565119
DOI: 10.1055/a-2256-6589 -
Cancer Communications (London, England) Mar 2024
Topics: Humans; Atovaquone; Tumor Microenvironment; Energy Metabolism; Mitochondria; Lung Neoplasms
PubMed: 37930151
DOI: 10.1002/cac2.12500 -
Animals : An Open Access Journal From... Nov 2023Avian malaria is a re-emerging threat to avian species worldwide. It is sustained by several protozoan species belonging to the genus , mainly . The even wider diffusion...
Avian malaria is a re-emerging threat to avian species worldwide. It is sustained by several protozoan species belonging to the genus , mainly . The even wider diffusion of the disease, probably because of the increase in the areas covered by their mosquito vectors, may pose new risks for avian species lacking natural resistance (especially those from artic or sub-artic environments) or those hosted in structures like zoos and wildlife rescue centers. With that premise, this study describes the efficacy and safety of a therapeutic protocol to treat avian malaria in three snowy owls () hosted in a wildlife rescue center in Apulia, south of Italy, and affected by avian malaria by . The protocol consisted of administering 10/4 mg/kg atovaquone/proguanil per os once a day for three consecutive days, repeating this seven days later. Seven days after the end of the treatment, was not detected in the birds' blood and no adverse effects were observed during the 60 days of monitoring after the end of the treatment. Therefore, a therapeutic regimen of 10/4 mg/kg/day may be considered safe and effective in a valuable and endangered species such as .
PubMed: 38003076
DOI: 10.3390/ani13223457 -
Emerging Infectious Diseases Oct 2023A 55-year-old man sought treatment for an uncomplicated febrile illness after returning to Canada from the Philippines. A suspected diagnosis of Plasmodium knowlesi... (Review)
Review
A 55-year-old man sought treatment for an uncomplicated febrile illness after returning to Canada from the Philippines. A suspected diagnosis of Plasmodium knowlesi infection was confirmed by PCR, and treatment with atovaquone/proguanil brought successful recovery. We review the evolving epidemiology of P. knowlesi malaria in the Philippines, specifically within Palawan Island.
Topics: Male; Humans; Middle Aged; Philippines; Plasmodium knowlesi; Malaria; Canada; Polymerase Chain Reaction
PubMed: 37735805
DOI: 10.3201/eid2910.230809 -
Cancer & Metabolism May 2024Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS)...
BACKGROUND
Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities. To improve the therapeutic benefit, FDA approved OXPHOS inhibitors (e.g. atovaquone) were conjugated to triphenylphosphonium (TPP) to preferentially target cancer cell's mitochondria. In this study, we evaluated the hypoxia reducing effects of several mitochondria-targeted OXPHOS inhibitors and compared them to non-mitochondria-targeted OXPHOS inhibitors using newly developed spheroid models for diffusion-limited hypoxia.
METHODS
B16OVA murine melanoma cells and MC38 murine colon cancer cells expressing a HIF-Responsive Element (HRE)-induced Green Fluorescent Protein (GFP) with an oxygen-dependent degradation domain (HRE-eGFP-ODD) were generated to assess diffusion-limited hypoxia dynamics in spheroids. Spheroids were treated with IACS-010759, atovaquone, metformin, tamoxifen or with mitochondria-targeted atovaquone (Mito-ATO), PEGylated mitochondria-targeted atovaquone (Mito-PEG-ATO) or mitochondria-targeted tamoxifen (MitoTam). Hypoxia dynamics were followed and quantified over time using the IncuCyte Zoom Live Cell-Imaging system.
RESULTS
Hypoxic cores developed in B16OVA.HRE and MC38.HRE spheroids within 24 h hours after seeding. Treatment with IACS-010759, metformin, atovaquone, Mito-PEG-ATO and MitoTam showed a dose-dependent reduction of hypoxia in both B16OVA.HRE and MC38.HRE spheroids. Mito-ATO only alleviated hypoxia in MC38.HRE spheroids while tamoxifen was not able to reduce hypoxia in any of the spheroid models. The mitochondria-targeted OXPHOS inhibitors demonstrated stronger anti-hypoxic effects compared to the non-mito-targeted OXPHOS inhibitors.
CONCLUSIONS
We successfully developed a high-throughput spheroid model in which hypoxia dynamics can be quantified over time. Using this model, we showed that the mitochondria-targeted OXPHOS inhibitors Mito-ATO, Mito-PEG-ATO and MitoTam reduce hypoxia in tumor cells in a dose-dependent manner, potentially sensitizing hypoxic tumor cells for radiotherapy.
PubMed: 38702787
DOI: 10.1186/s40170-024-00342-6 -
International Journal of Pharmaceutics Apr 2024Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to...
Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA). ATO by interrupting the electron transfer in OXPHOS could suppress mitochondrial respiration of tumor cells, economising on oxygen for the generation of ROS. Benefiting from the mitochondrial targeting function of TPP, ATO was directly delivered to its site of action to obtain highlighted effect at a lower dosage. Furthermore, positioning the photosensitizer IR780 to mitochondria, a more vulnerable organelle to ROS, was a promising method to attenuate the spatiotemporal limitation of ROS caused by its short half-life and narrow diffusion radius. As a result, TNPs/IA exhibited accurate subcellular localization, lead to the collapse of ATP production by damaging mitochondrion and elicited significant antitumor efficacy via oxygen-augmented PDT in the HeLa subcutaneous xenograft model. Overall, TNPs/IA was a potential strategy in photodynamic eradication of tumors.
Topics: Humans; Photochemotherapy; Reactive Oxygen Species; Oxidative Phosphorylation; Photosensitizing Agents; Nanoparticles; Oxygen; Hypoxia; Cell Line, Tumor
PubMed: 38432451
DOI: 10.1016/j.ijpharm.2024.123943 -
The American Journal of Tropical... Oct 2023Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million...
Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million infections each year. We sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation. We administered questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia. Questions explored preferences and concerns around long-acting antimalarial formulations compared with oral formulations. We recruited 202 patient respondents (Kenya, n = 102; Zambia, n = 100) and 215 provider respondents (Kenya, n = 105; Zambia, n = 110). Long-acting injection was preferred to oral pills, whereas oral pills were preferred to implant or transdermal administration by patient respondents. Of 202 patient respondents, 80% indicated that they 'definitely would try' malaria chemoprevention offered by injection instead of oral pills. Of parents or guardians, 84% of 113 responded that they 'definitely would' have their child age < 12 years and 90% of 88 'definitely would' have their child ≥12 years receive an injection for malaria prevention. Provider respondents indicated that they would be more likely to prescribe a long-acting injectable product compared with an oral product for malaria chemoprevention in adults (70%), adolescents ages 12 years and older (67%), and children <12 years (81%). Potential for prolonged adverse effects with long-acting products was the highest concern for patient respondents, while higher medication-related cost was cited as the most concerning barrier to implementation by providers. Overall, these findings indicate enthusiasm for the development of long-acting injectable antimalarials to provide individual delivery method options across age groups.
Topics: Child; Adult; Adolescent; Humans; Antimalarials; Malaria; Chemoprevention; Zambia; Injections
PubMed: 37604474
DOI: 10.4269/ajtmh.23-0245 -
International Journal of Antimicrobial... Sep 2023In the absence of a highly efficacious vaccine, chemotherapy remains the cornerstone to control malaria morbidity and mortality. The threat of the emergence of parasites...
In the absence of a highly efficacious vaccine, chemotherapy remains the cornerstone to control malaria morbidity and mortality. The threat of the emergence of parasites resistant to artemisinin-based combination therapies highlights the need for new antimalarial drugs ideally with superior properties. The killing rate reflects the speed of action of antimalarial drugs, which can be measured in vitro through the parasite reduction ratio (PRR) assay to shortlist interesting candidates. As a standard, the in vitro PRR assay is performed by measuring [H]hypoxanthine incorporation of Plasmodium falciparum. This methodology is restricted to specialised laboratories owing to the handling of radioactive material. In this work, we describe a sandwich enzyme-linked immunosorbent assay to detect P. falciparum histidine-rich protein 2 (HRP-2) as an alternative methodology to assess the PRR. We first validated the methodology with established antimalarial drugs (artesunate, chloroquine, pyrimethamine and atovaquone) by comparing our results with previous results of the [H]hypoxanthine incorporation readout provided by an expert laboratory, and subsequently assessed the speed of action of four new antimalarial candidates (compound 22, chlorotonil A, boromycin and ivermectin). The HRP-2 PRR assay achieved comparable results to the [H]hypoxanthine incorporation readout in terms of parasite growth rate over time, lag phase and parasite clearance time. In addition, parasite growth following drug exposure was quantified after 7, 14, 21 and 28 days of recovery time. In conclusion, the PRR assay based on HRP-2 is similar to [H]hypoxanthine in determining a drug's parasite killing rate and can be widely used in all research laboratories.
Topics: Animals; Antimalarials; Parasites; Plasmodium falciparum; Hypoxanthine; Chloroquine; Malaria, Falciparum
PubMed: 37348620
DOI: 10.1016/j.ijantimicag.2023.106894