Assessing the impact of severe acute respiratory syndrome coronavirus 2 infection on hematological parameters.

BACKGROUND: The current study is a retrospective study designed to evaluate changes in complete blood count and coagulation parameters in adult coronavirus disease 2019 (COVID-19) patients at a prominent Saudi tertiary center to predict disease severity and mortality. METHODS: The cohort consisted of 74 800 adult patients divided into four groups based on a COVID-19 test and the patient's sex: 35 985 in the female negative COVID-19 group, 23 278 in the male negative COVID-19 group, 8846 in the female positive COVID-19 group and 6691 in the male positive COVID-19 group. RESULTS: Patients with COVID-19 demonstrated decreased white blood cell counts and increased red blood cell counts. Also, COVID-19-positive participants exhibited more prolonged partial thromboplastin time and lower D-dimer levels than those of COVID-19-negative subjects (p<0.05). The study also revealed gender-dependent impacts on platelet counts, implying a possible relationship with the greater infection mortality rate in men than in women (p<0.001). In addition, the study found a link between changes in coagulation test results and death in COVID-19 patients (p<0.001). The evidence regarding the effects of COVID-19 on blood cell counts and coagulation, on the other hand, is conflicting, most likely due to variances in study populations and the timing of testing postinfection. CONCLUSIONS: According to the findings, COVID-19-related alterations in blood cell count and clotting ability may be risk factors for death.

Assessing the impact of COVID-19 on acute leukemia patients: a comparative analysis of hematological and biochemical parameters.

BACKGROUND: The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia. METHODS: This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained. RESULTS: The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2. CONCLUSION: While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.

Assessing the Impact of COVID-19 Vaccines on Sickle Cell Anaemia Patients: A Comparative Analysis of Biochemical and Haematological Parameters.

The coronavirus disease 2019 (COVID-19) vaccines have been developed to help prevent the spread of the virus infections. The COVID-19 vaccines, including Pfizer, Moderna, and AstraZeneca, have undergone rigorous testing and have demonstrated both safety and effectiveness. Extensive evidence supports their effectiveness in preventing severe illness, hospitalization, and mortality associated with COVID-19 infection. The administration of COVID-19 vaccines can directly affect hematological and biochemical parameters, with reported cases showing an association with thrombosis and thrombocytopenia. Therefore, it was hypothesized that COVID-19 vaccines may also influence hematological and biochemical markers in sickle cell patients. This study aimed to investigate the side effects of COVID-19 vaccines on sickle cell patients, providing a comprehensive evaluation of hematological and biochemical parameters. To our knowledge, this is the first study of its kind conducted in Saudi Arabia. The study included the evaluation of Pfizer and Oxford-AstraZeneca vaccines in sickle cell patients, measuring key parameters. Our findings revealed varying impacts of both vaccines on the ALT, AST, and CRP levels. Notably, CRP and ALT exhibited potential as indicators for renal disease, diabetes, and arthritis. However, further investigations are necessary to uncover the underlying mechanisms that drive these observed differences and comprehend their clinical implications for this vulnerable patient population. The unique nature of our study fills a crucial research gap and underscores the need for additional research in this area.

Implications of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Hospitalised Patients with Co-Infections and Clinical Outcomes.

The clinical severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may rise because of acquiring a co-infection during the hospital stay of the patients. The rate of hospital co-infection alongside COVID-19 infection remains low. However, the mortality rates and intensive care unit (ICU) admission remains ambiguous. The present study investigates the implications of COVID-19 hospitalised infected patients with co-infection and the clinical outcomes. In this study, 142 patients were included. The eligible patients who tested positive for COVID-19 infection were hospitalised for more than two days. Each patient's characteristics and laboratory results were collected, such as who was admitted to the intensive care unit and who was discharged or expired. The results revealed that out of the 142 hospitalised patients, 25 (17.6%) were co-infection positive, and 12 identified types of co-infection: two Gram-positive bacterial infections, one fungal infection and nine Gram-negative bacterial infections. In addition, 33 (23.2%) were ICU admitted, 21 were co-infection negative and 12 were co-infection positive. Among the 12 ICU admitted with co-infection, 33.4% were discharged. The death rate and ICU admission had a p-value < 0.05, indicating statistical significance for co-infected patients compared to non-co-infected patients. It was concluded that co-infection remains very low within hospitalised COVID-19-infected patients but can have severe outcomes with increased ICU admission and increased mortality rates. Thus, implementing infection preventive measures to minimize the spread of hospital-acquired infections among COVID-19 hospitalised patients.

Risk Factors for Glucose 6-Phosphate Dehydrogenase and COVID-19 Disease-A Retrospective Study at a Major Saudi Tertiary Center.

Glucose-6-phosphate dehydrogenase (G6PD) insufficiency is a common enzymatic defect worldwide; it affects over 400 million people and is associated with various disorders. Recent research suggests that G6PD-deficient cells are susceptible to infection by human coronaviruses, as the G6PD enzyme is involved in the metabolism of oxidative stress, which may enhance COVID-19 mortality. This retrospective study aimed to examine the effect of COVID-19 on patients with G6PD deficiency by comparing the laboratory parameters of patients with G6PD enzyme deficiency alone, COVID-19 alone, and those with both COVID-19 and G6PD enzyme deficiency treated at a major Saudi tertiary center. The results indicated significant differences in hematological and biochemical parameters between the three patient groups, indicating that COVID-19 may influence these parameters, and that they could be used to measure the severity of COVID-19 disease. Moreover, this study suggests that patients with G6PD enzyme deficiency may be at higher risk for severe COVID-19 outcomes. Although the study is limited by the lack of a random selection method for group membership, the Kruskal-Wallis H-test was used to statistical assess the data. The study's findings can enhance the understanding of the relation between COVID-19 infected and G6PD-deficiency patients and inform clinical decision making for an improved patient outcome.

Hospital-Acquired Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Observational Study.

Worldwide, hospital-acquired infections (HAIs) are continuously rising within healthcare settings, leading to high mortality and morbidity rates. Many hospitals have reported the spread of carbapenemases globally, specifically within the E. coli and K. pneumoniae species. This study was aimed at analyzing the state of hospital-acquired, carbapenem-resistant E. coli and K. pneumoniae in the United Kingdom between 2009 and 2021. Moreover, the study analyzed the most efficacious approaches to patient management for controlling the carbapenem-resistant Enterobacteriaceae (CRE) spread. Initially, 1094 articles were identified as relevant for screening, and among them, 49 papers were eligible for full-text screening, with a total of 14 articles meeting the inclusion criteria. The information was recorded from published articles through PubMed, the Web of Science, Scopus, Science Direct, and the Cochrane library and was used to search for hospital-acquired carbapenem-resistant E. coli and K pneumoniae in the UK between 2009 and 2021, in order to evaluate the spread of CRE in hospitals. The total number of carbapenem-resistant E. coli was 1083 and this was 2053 for carbapenem-resistant K. pneumoniae in more than 63 UK hospitals. KPC was the dominant carbapenemase produced by K. pneumoniae. The results showed that the treatment options considered depended on the type of carbapenemase produced; K. pneumoniae showed more resistance to a treatment options, i.e., Colistin, than the other carbapenemase. The current state of the UK is at minimal risk for a CRE outbreak; however, appropriate treatment and infection control measures are highly required to prevent this CRE spread at the regional and global levels. The present study findings have an important message for physicians, healthcare workers, and policymakers about hospital-acquired carbapenem-resistant E. coli and K. pneumoniae spread and approaches to patient management.

The Risk Factors for Acute Cerebrovascular Accident (Stroke) in Patients with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2).

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) patients may experience an acute ischemic stroke; however, risk factors, in-hospital deaths, and outcomes have not been thoroughly investigated. This study investigates the risk factors, comorbidities, and outcomes in patients with SARS-VoV-2 infection and acute ischemic stroke compared to patients without these conditions. The present retrospective study was conducted in the King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard, Health Affairs, Riyadh, Saudi Arabia, during the period from April 2020 to February 2022. This study investigates the risk variables among the individuals who were diagnosed with either SARS-CoV-2 with stroke or patients with stroke alone. A total of 42,688 COVID-19 patients were registered, 187 cases of strokes were listed in COVID-19 patients, however, 5395 cases with stroke without SARS-CoV-2 infection. The results revealed that factors including age, hypertension, deep vein thrombosis, and ischemic heart disease are associated with an increased risk of ischemic stroke. The results also displayed an elevated frequency of in-hospital deaths in COVID-19 patients with acute ischemic stroke. The results also showed that SARS-CoV-2 together predicts the probability of stroke and death in the study sample. The study findings conclude that ischemic strokes were infrequent in patients with SARS-CoV-2 and usually occur in the presence of other risk factors. The risk factors of ischemic strokes in patients with SARS-CoV-2 are old age, male gender, hypertension, hyperlipidaemia, DVT, ischemic heart disease, and diabetes mellitus. Furthermore, the results showed a higher frequency of in-hospital deaths in COVID-19 patients with stroke compared to COVID-19 patients without stroke.

Evaluating the Adverse Events Associated with Three Doses of the COVID-19 Vaccination in Adults in the Western Region of Saudi Arabia: A Cross-Sectional Study.

The Kingdom of Saudi Arabia was one of the countries earliest affected by the coronavirus 2019 (COVID-19) pandemic and had taken precautions including compulsory COVID-19 vaccination. Both the ChAdOx1 nCoV-19 vaccine (Oxford AstraZeneca) and the BNT162b2 vaccine (Pfizer) were approved by the Saudi Ministry of Health, followed by mRNA-1273 (Moderna), all of which were used for population-wide vaccination. This study aimed to assess the short-term side effects following the COVID-19 vaccinations among participants who had received all three doses in the western region of Saudi Arabia. An online survey was distributed to the participants who received either BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273 vaccines, and the type of side effects and their severity were evaluated. Fatigue and headache, pain at the site of the injection and muscle pain were the most common side effects in all three doses. However, the severity depending on the type of vaccination was significant only for the first and second dose, but not the third dose. In contrast, there was a higher percentage of participants who encountered severe side effects from the third dose compared to the first and second. Nevertheless, the majority of participants described all three doses' side effects to be moderately severe. A future evaluation could be made to access the individual types of vaccination and compare between the side effects of the BNT162b2, ChAdOx1 nCoV-19, and mRNA-1273 vaccines specifically for the booster dose.

Problems in Malaysian children with large angle infantile esotropia: Children and parents' perspectives.

INTRODUCTION: There is limited information regarding the problems faced by children with large angle infantile esotropia (LAIE). The aim of this study was to explore the problems that children with LAIE encounter from both their perspectives and those of their parents. METHODS: This study included children who had LAIE (with angle of 40 prism dioptres or greater), aged 5 and 17 years who had attended the Ophthalmology Clinic, Hospital Universiti Sains Malaysia from March to September 2016. The children and their parents or guardians were interviewed face-to-face using a validated semi-structured interview guide. Interviews were tape-recorded and transcribed verbatim. Content analysis was performed using the NVivo 12 software. RESULTS: A total of 30 children and 30 parents were interviewed. The most common problems identified by the children were social interactions (73.3%, 22 children), visual functions (60.0%, 18 children), emotions (60.0%, 18 children), physical issues (40.0%, 12 children) and difficulties regarding treatment options (26.7%, eight children). The parents reported that their children were more affected in terms of visual functions (100.0%, 30 parents), social interactions (56.7%, 17 parents), emotions (43.3%, 13 parents), physical issues (20.0%, six parents), and difficulties regarding treatment options (16.7%, five parents). CONCLUSION: The major problems that the children with LAIE identified were social interactions, while the parents observed that problems with visual functions was the most common issue encountered by their children. This suggests that the children affected have different perspectives from their parents and require support.

Selective laser trabeculoplasty vs. topical medications for step-up treatment in primary open angle glaucoma: comparing clinical effectiveness, quality of life and cost-effectiveness.

INTRODUCTION: The aim of this study was to investigate the clinical effectiveness, health related quality of life (HRQoL) and cost effectiveness of selective laser trabeculoplasty (SLT) compared to topical anti-glaucoma medications in step-up treatment of patients with primary open angle glaucoma (POAG). METHODS: Seventeen POAG patients with suboptimal IOP control despite pre-existing topical medications were subjected to adjunct SLT (50 applications 180 degrees) or second line medical therapy. Current medications were continued, and patients were followed up for 6 months for degree of intraocular pressure (IOP) lowering. HRQoL was assessed using Glaucoma Quality of Life 36-item (GlauQoL-36), Assessment of Quality of Life-7D (AQoL-7D) and Vision related Quality of Life (VisQoL). Costs involved were calculated and compared to the effect (IOP reduction) achieved in each arm. RESULTS: Ten patients were in the SLT group and 7 in the topical medication (MED) group. Mean baseline intraocular pressure (IOP) was 18.90±3.48mmHg in SLT group and 15.57±2.23mmHg in MED group. Mean reduction of IOP was 4.30±1.64mmHg in SLT group and 2.71±2.56 mmHg in MED group at 6 months which was not statistically significant (p=0.14) between two groups. All the HRQoL questionnaires did not show significant changes in the groups or between groups when compared baseline with 6-month post treatment (p-values ranging from 0.247 to 0.987). For every 1mmHg reduction in IOP, cost involved in MED group (RM53.61) was 165% of the cost involved in SLT group (RM32.56). DISCUSSION AND CONCLUSION: This study has shown that SLT was as effective clinically and tolerable as topical anti glaucoma medications and was possibly more cost effective in the step-up treatment of patients with POAG at 6 months follow- up.

Various Ways of Continuous Intraocular Pressure Monitoring in Glaucoma Patients: A Narrative Review

@#Glaukoma adalah sejenis penyakit neurodegeneratif yang berlaku akibat ketidakseimbangan dalam peredaran cecair akues yang disebabkan oleh resistan pada sistem pengaliran keluar cecair tersebut. Ini meningkatkan tekanan intraokular (TIO) yang menyebabkan kerosakan pada saraf optik dan seterusnya mengakibatkan kebutaan yang kekal. Oleh kerana TIO adalah satu faktor risiko glaukoma yang boleh dikawal, ciri-ciri dan variasi tekanan sepanjang 24 jam perlu dikenalpasti sebelum rawatan dimulakan. Pemantauan TIO adalah satu aspek yang terpenting dan kritikal dalam pengurusan glaukoma. Pelbagai tindakan kawalan melalui penggunaan teknologi yang berbeza telah dan sedang dilakukan untuk pemantauan TIO yang kerap dan berterusan selama 24 jam untuk menentukan kewujudan TIO yang tinggi (peak) dan fluktuasi tekanan. Artikel ini bertujuan untuk meninjau pendekatan inovatif yang terkini serta untuk mengulas kepentingan dan kelemahan setiap teknik bagi memperolehi profil TIO selama 24 jam.

Transtumoral targeting enabled by a novel neuropilin-binding peptide.

We have recently described a class of peptides that improve drug delivery by increasing penetration of drugs into solid tumors. These peptides contain a C-terminal C-end Rule (CendR) sequence motif (R/K)XX(R/K), which is responsible for cell internalization and tissue-penetration activity. Tumor-specific CendR peptides contain both a tumor-homing motif and a cryptic CendR motif that is proteolytically unmasked in tumor tissue. A previously described cyclic tumor-homing peptide, LyP-1 (sequence: CGNKRTRGC), contains a CendR element and is capable of tissue penetration. We use here the truncated form of LyP-1, in which the CendR motif is exposed (CGNKRTR; tLyP-1), and show that both LyP-1 and tLyP-1 internalize into cells through the neuropilin-1-dependent CendR internalization pathway. Moreover, we show that neuropilin-2 also binds tLyP-1 and that this binding equally activates the CendR pathway. Fluorescein-labeled tLyP-1 peptide and tLyP-1-conjugated nanoparticles show robust and selective homing to tumors, penetrating from the blood vessels into the tumor parenchyma. The truncated peptide is more potent in this regard than the parent peptide LyP-1. tLyP-1 furthermore improves extravasation of a co-injected nanoparticle into the tumor tissue. These properties make tLyP-1 a promising tool for targeted delivery of therapeutic and diagnostic agents to breast cancers and perhaps other types of tumors.

Magnetic susceptibility of iron in malaria-infected red blood cells.

During intra-erythrocytic maturation, malaria parasites catabolize up to 80% of cellular haemoglobin. Haem is liberated inside the parasite and converted to haemozoin, preventing haem iron from participating in cell-damaging reactions. Several experimental techniques exploit the relatively large paramagnetic susceptibility of malaria-infected cells as a means of sorting cells or investigating haemoglobin degradation, but the source of the dramatic increase in cellular magnetic susceptibility during parasite growth has not been unequivocally determined. Plasmodium falciparum cultures were enriched using high-gradient magnetic fractionation columns and the magnetic susceptibility of cell contents was directly measured. The forms of haem iron in the erythrocytes were quantified spectroscopically. In the 3D7 laboratory strain, the parasites converted approximately 60% of host cell haemoglobin to haemozoin and this product was the primary source of the increase in cell magnetic susceptibility. Haemozoin iron was found to have a magnetic susceptibility of (11.0+/-0.9)x10(-3) mL mol(-1). The calculated volumetric magnetic susceptibility (SI units) of the magnetically enriched cells was (1.88+/-0.60)x10(-6) relative to water while that of uninfected cells was not significantly different from water. Magnetic enrichment of parasitised cells can therefore be considered dependent primarily on the magnetic susceptibility of the parasitised cells.

Ex vivo growth of rabbit bulbar, fornix and palpebral conjunctival epithelia in a serum-free and feeder layer-free culture system.

This study was conducted to explore the feasibility of culturing conjunctiva epithelial cells in serum-free and feeder layer-free culture system with regard to the cell morphology and immunocytochemistry of the rabbit bulbar, fornix and palpebral conjunctiva epithelia. The results showed that epithelium cells from all the three conjunctiva regions can be cultured in a serum-free and feeder layer-free environment. We obtained highest epithelial growth from fornix region with minimum invasion of fibroblast cells compared to other area. All cultured cells were stained positive for cytokeratin 19 and MUC5AC and negative for cytokeratin 3. These findings suggested that fornix was a better source of cells for the development of tissue engineered conjunctiva for future clinical application.

Retinol supplementation in murine Plasmodium berghei malaria: effects on tissue levels, parasitaemia and lipid peroxidation.

Reduced plasma retinol concentrations occur in human malaria but the benefits of supplementation remain uncertain. We assessed the in vivo efficacy of retinol administration, and its effect on lipid peroxidation, in a Plasmodium berghei murine model. Animals received vehicle (n=17) or retinol (i) before P. berghei inoculation (four doses), (ii) at parasitaemia 10-15% (three to four doses) or (iii) before and after inoculation (six to seven doses; n=15 in each group), with euthanasia on day 8 post-inoculation or when the parasitaemia exceeded 50%. Multiple-dose pre-inoculation retinol reduced endpoint parasitaemia by 24% (P=0.001 versus controls). A reduction of 18% (P=0.042) was observed when retinol was given to parasitaemic animals. Retinol was ineffective when given both before and after infection (11% reduction; P=0.47). Although retinol supplementation did not change plasma retinol concentrations, liver retinol content increased and correlated inversely with endpoint parasitaemia (r=-0.45, P=0.001). Malaria infection augmented concentrations of the free radical lipid peroxidation end-product F(2)-isoprostanes in plasma, erythrocytes and liver by 1.8-, 2.8- and 4.9-fold, respectively, but retinol supplementation had no effect on these increases. Consistent with some human malaria studies, prophylactic retinol reduces P. berghei parasitaemia. This effect relates to augmentation of tissue retinol stores rather than to retinol-associated changes in oxidant status.

Characterization of the effect of retinol on Plasmodium falciparum in vitro.

A preliminary study from our laboratory found retinol (vitamin A alcohol) to have in vitro activity against Plasmodium falciparum at concentrations close to those in normal human serum (1-3 microM). To characterize the antimalarial potential of retinol in more detail, the 3D7 and K1 laboratory strains of P. falciparum were maintained in continuous culture and [3H]hypoxanthine incorporation and microscopy were used to assess the effect of retinol against asexual stages of the parasite life-cycle. Losses of retinol and retinol-associated hemolysis were also quantified in the in vitro culture system. There were retinol losses of >50% but no hemolysis was observed with added retinol concentrations up to 100 microM. All stages of parasite development showed comparable sensitivity to retinol including merozoite invasion (range of mean IC50 values 10.1-21.4 microM after adjustment for losses). Retinol pre-treatment of uninfected RBC did not inhibit merozoite invasion. Retinol treatment was associated with increased vacuolization within the parasite food vacuole and evidence of parasite membrane rupture. These appearances were similar to those seen with quinoline and artemisinin compounds. Although these data do not support a role for acute retinol supplementation in the treatment of falciparum malaria, they add to knowledge regarding potential antimalarial therapies and justify assessment of more potent synthetic retinoids and their metabolites.

In vitro antimalarial activity of retinoids and the influence of selective retinoic acid receptor antagonists.

Retinol (vitamin A alcohol) may have a beneficial role in the host response to malaria in humans and previously published data have suggested that it has a direct inhibitory effect on the growth of Plasmodium falciparum in vitro. To further investigate the role of retinoids as potential antimalarial agents, we assessed the effect of all-trans-retinoic acid (RA), 9-cis-RA and 13-cis-RA, as well as retinol itself and its ester, retinyl palmitate, on 3H-hypoxanthine uptake by the laboratory-adapted strains of P. falciparum 3D7 and K1. In addition, we examined the influence of three specific RA receptor antagonists, ER 27191, Ro 415253 and AGN 194301, on retinoid-induced growth inhibition of 3D7. All-trans-RA, 9-cis-RA and 13-cis-RA in concentrations ranging from 1 x 10(-4) to 5 x 10(-10) M each had antimalarial activity, but at IC50 values (5.9 x 10(-5) to 7.9 x 10(-5) M) that were less than those of retinol (2.5 x 10(-5) to 3.2 x 10(-5) M). Retinyl palmitate had minimal effect on 3H-hypoxanthine uptake. Each of the three specific antagonists inhibited growth of 3D7 (IC50 range 1.2 x 10(-5) to 3.0 x 10(-5) M) but, in isobolographic analysis, were antagonistic to retinol (dose factor potentiation, DFP 0.46-0.79) and, in the case of Ro 415253, to all-trans-RA (DFP=0.39). Although we did not attempt to quantify losses of retinoids from the system, these data suggest that retinol has greater antimalarial activity than its RA metabolites and especially retinyl palmitate. The specific RA receptor antagonists showed paradoxical antimalarial activity but consistently antagonised the effect of retinol and all-trans-RA in isobolographic experiments. We conclude that RA metabolites may be less suitable than retinol per se as antimalarial agents and that P. falciparum might possess or acquire a RA receptor-like moiety.

In vitro antimalarial activity of trovafloxacin, a fourth-generation fluoroquinolone.

Trovafloxacin, a recently-developed fourth-generation fluoroquinolone, is more potent than other quinolone drugs against a wide range of organisms including Toxoplasma gondii. We assessed the in vitro antimalarial activity of trovafloxacin against three laboratory-adapted Plasmodium falciparum isolates and compared the results with those of ciprofloxacin and norfloxacin. Synchronous and asynchronous cultures were exposed to a range of drug concentrations, and growth inhibition was assessed using 3H-hypoxanthine incorporation. All isolates, both synchronous and asynchronous, exhibited comparable sensitivities with trovafloxacin (EC50 range, 1.8 x 10(-5) to 3.7 x 10(-5) mol/l) and ciprofloxacin (2.0 x 10(-5) to 3.9 x 10(-5) mol/l), but were less sensitive to norfloxacin (5.4 x 10(-5) to 6.6 x 10(-4) mol/l). These results confirm that ciprofloxacin is twice as potent as norfloxacin against P. falciparum in vitro, but also show that trovafloxacin and ciprofloxacin have similar antimalarial potency. The EC50 concentrations of all three drugs were generally higher than those achieved after conventional doses in humans, suggesting that their clinical application may be limited to combination therapy. Recent reports of hepatotoxicity with trovafloxacin may also prevent the use of this drug in humans. However, newer fourth-generation quinolones may prove safer and have similar antimalarial potency.