Therapeutic efficacy of pyronaridine-artesunate (Pyramax®) against uncomplicated Plasmodium falciparum infection at Hamusit Health Centre, Northwest Ethiopia.

BACKGROUND: Early case detection and prompt treatment are important malaria control and elimination strategies. However, the emergence and rapid spread of drug-resistant strains present a major challenge. This study reports the first therapeutic efficacy profile of pyronaridine-artesunate against uncomplicated Plasmodium falciparum in Northwest Ethiopia. METHODS: This single-arm prospective study with 42-day follow-up period was conducted from March to May 2021 at Hamusit Health Centre using the World Health Organization (WHO) therapeutic efficacy study protocol. A total of 90 adults ages 18 and older with uncomplicated falciparum malaria consented and were enrolled in the study. A standard single-dose regimen of pyronaridine-artesunate was administered daily for 3 days, and clinical and parasitological outcomes were assessed over 42 days of follow-up. Thick and thin blood films were prepared from capillary blood and examined using light microscopy. Haemoglobin was measured and dried blood spots were collected on day 0 and on the day of failure. RESULTS: Out of 90 patients, 86/90 (95.6%) completed the 42-day follow-up study period. The overall PCR-corrected cure rate (adequate clinical and parasitological response) was very high at 86/87 (98.9%) (95% CI: 92.2-99.8%) with no serious adverse events. The parasite clearance rate was high with fast resolution of clinical symptoms; 86/90 (95.6%) and 100% of the study participants cleared parasitaemia and fever on day 3, respectively. CONCLUSION: Pyronaridine-artesunate was highly efficacious and safe against uncomplicated P. falciparum in this study population.

Efficacy and safety of pyronaridine-artesunate (Pyramax®) for the treatment of uncomplicated Plasmodium vivax malaria in Northwest Ethiopia.

BACKGROUND: Declining efficacy of chloroquine for the treatment Plasmodium vivax malaria has been reported in different endemic settings in Ethiopia. This highlights the need to assess alternative options for P. vivax treatment with artemisinin-based combination therapy, such as pyronaridine-artesunate. This treatment regimen has shown high efficacy for uncomplicated malaria in both Africa and Asia. However, limited data are available from Ethiopia. This study was conducted to assess the efficacy and safety of pyronaridine-artesunate for the treatment of uncomplicated P. vivax malaria in Northwest Ethiopia. METHODS: A single arm prospective efficacy study was conducted in the Hamusite area, Northwest Ethiopia. Fifty-one febrile adult patients with uncomplicated P. vivax malaria were enrolled between March and July 2021. Patients were treated with pyronaridine-artesunate once daily for three days. Clinical and parasitological parameters were monitored over a 42-day follow-up period using the standard World Health Organization protocol for therapeutic efficacy studies. RESULTS: A total of 4372 febrile patients were screened with 51 patients enrolled and 49 completing the 42-day follow-up period. The PCR-uncorrected adequate clinical and parasitological response (ACPR) was 95.9% (47/49; 95% CI 84.9-99.0) on day 42. Two patients had recurrences [4.0% (2/49); 95% CI 0.7-12.1] on days 35 and 42. The parasite clearance rate was rapid with fast resolution of clinical symptoms; 100% of participants had cleared parasitaemia on day 1 and fever on day 2. All 16 (31.4%) patients with gametocyte carriage on day 0 had cleared by day 1. There were no serious adverse events. CONCLUSION: In this small study, pyronaridine-artesunate was efficacious and well-tolerated for the treatment of uncomplicated P. vivax malaria. In adults in the study setting, it would be a suitable alternative option for case management.

Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis.

Introduction: Inflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies. Methods: A comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks' funnel plot. Fagan's nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity. Result: A total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn's disease (CD). Conclusion: LncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840.

Uro-pathogens: Multidrug resistance and associated factors of community-acquired UTI among HIV patients attending antiretroviral therapy in Dessie Comprehensive Specialized Hospital, Northeast Ethiopia.

BACKGROUND: Urinary tract infections are common bacterial and fungal infections in humans, occurring both in the community and in immunocompromised patients in healthcare settings. Urinary tract infections have a significant health impact on HIV-infected patients. Nowadays, drug-resistant pathogens are widespread poses a serious clinical risk, and causes urinary tract infection. The common agents of bacteria and fungi that cause urinary tract infection are Escherichia coli followed by Klebsiella pneumonia, Staphylococcus saprophyticus, Enterococcus faecalis, group B streptococcus, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida. albicans. This study aimed to investigate uro-pathogen, multidrug resistance pattern of bacteria, and associated factors of community-acquired urinary tract infection among HIV-positive patients attending antiretroviral therapy in Dessie comprehensive specialized hospital, Northeast Ethiopia from February 1, 2021, to March 30, 2021. METHODS: An institutional-based cross-sectional study was conducted at Dessie Comprehensive Specialized Hospital. Socio-demographic and clinical data were collected by using structured questionnaires from HIV patients suspected of community-acquired urinary tract infections. About 10 ml of clean-catch midstream urine was collected and inoculated into Blood agar, MacConkey, and Cysteine lactose electrolyte deficient media. Yeasts were identified by using Gram stain, germ tube test, carbohydrate fermentation, assimilation tests, and chromogenic medium. Gram stain and biochemical tests were performed to identify isolates and an antimicrobial susceptibility pattern was performed on disc diffusion techniques. Data were entered and analyzed using SPSS version 25. Both bivariate and multivariable logistic regression analysis was performed and a P value of < 0.05 with an adjusted odds ratio with their 95% confidence interval (CI) was used as statistically significant associations. RESULTS: From the total 346 study participants, 92 (26.6%) were culture positive 75 (81.52%) were bacterial and 17 (18.48%) were fungal pathogens. From a total of 75 bacteria isolates 51(68%) were Gram-negative bacteria and the most commonly isolated bacteria were E. coli 16 (21.33%) followed by K. pneumoniae 11(14.67%) and enterococcus species 10(10.87. Of the 17 fungal isolates of fungi, 8(47.1%) were represented by C. tropicalis. Of the isolated bacteria, 61(81.3%) were resistant to three and above classes of antibiotics (drug classes). About 13 (81.3%) of E. coli, 9(81.8%) of K. pneumoniae, 8(80%) of Enterococcus species, 7 (77.8%) of P. aeruginosa, and CoNs 7(87.5%) were the most frequently exhibited three and above classes of antibiotics (multi-drug resistance). Amikacin and gentamicin were effective against Gram-negative Uro-pathogens. Participants aged>44year, female, being daily labor, being farmer, unable to read and write, patients with CD4 count of ≤ 200 cells/mm3 and CD4 count of 201-350 cells/mm3, who had chronic diabetics, patients having a history of hospitalization and who had urgency of urinations were statistically significant association with significant urinary tract infections. CONCLUSION: The burden of community-acquired urinary tract infections among HIV patients is alarmingly increased. Therefore, behavior change communications might be considered for promoting the health status of HIV patients. Moreover, CD4 level monitoring and therapeutics selection based on microbiological culture are quite advisable for the management of urinary tract infections of HIV patients.