Chloroquine has shown high therapeutic efficacy against uncomplicated Plasmodium vivax malaria in southern Ethiopia: seven decades after its introduction.

BACKGROUND: Plasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia. METHODS: In 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28. RESULTS: A total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h. CONCLUSION: Despite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.

A narrative review of the phenomenon of predatory journals to create awareness among researchers in veterinary medicine.

In recent years, especially since the COVID-19 pandemic, the number of predatory journals has increased significantly. Predatory journals exploit the "open-access model" by engaging in deceptive practices such as charging high publication fees without providing the expected quality and performing insufficient or no peer review. Such behaviors undermine the integrity of scientific research and can result in researchers having trouble identifying reputable publication opportunities, particularly early-career researchers who struggle to understand and establish the correct criteria for publication in reputable journals. Publishing in journals that do not fully cover the criteria for scientific publication is also an ethical issue. This review aimed to describe the characteristics of predatory journals, differentiate between reliable and predatory journals, investigate the reasons that lead researchers to publish in predatory journals, evaluate the negative impact of predatory publications on the scientific community, and explore future perspectives. The authors also provide some considerations for researchers (particularly early-career researchers) when selecting journals for publication, explaining the role of metrics, databases, and artificial intelligence in manuscript preparation, with a specific focus on and relevance to publication in veterinary medicine.

Efficacy and safety of praziquantel treatment against Schistosoma mansoni infection among pre-school age children in southern Ethiopia.

BACKGROUND: Preventive chemotherapy with a single dose of praziquantel given to an all-at-risk population through mass drug administration is the cornerstone intervention to control and eliminate schistosomiasis as a public health problem. This intervention mainly targets school age children, and pre-school age children (pre-SAC) are excluded from receiving preventive chemotherapy, partly due to scarcity of data on praziquantel treatment outcomes. METHODS: We conducted active efficacy and safety surveillance of praziquantel treatment among 240 Schistosoma mansoni-infected pre-SAC who received a single dose of praziquantel (40 mg/kg) in southern Ethiopia. The study outcomes were egg reduction rates (ERR) and cure rates (CRs) four weeks after treatment using the Kato-Katz technique and treatment-associated adverse events (AEs) that occurred within 8 days post-treatment. RESULTS: The overall ERR was 93.3% (WHO reference threshold ≥ 90%), while the CR was 85.2% (95% CI = 80.0-89.5%). Baseline S. mansoni infection intensity was significantly associated with CRs, 100% among light infected than moderate (83.4%) or heavy (29.4%) infected children. An increase of 100 in baseline S. mansoni egg count per gram of stool resulted in a 26% (95% CI: 17%, 34%) reduction in the odds of cure. The incidence of experiencing at least one type of AE was 23.1% (95% CI: 18.0%, 29.0%). Stomachache, diarrhea, and nausea were the most common AEs. AEs were mild-to-moderate grade and transient. Pre-treatment moderate (ARR = 3.2, 95% CI: 1.69, 6.14) or heavy infection intensity (ARR = 6.5, 95% CI: 3.62, 11.52) was a significant predictor of AEs (p < 0.001). Sex, age, or soil-transmitted helminth coinfections were not significant predictors of CR or AEs. CONCLUSIONS: Single-dose praziquantel is tolerable and effective against S. mansoni infection among pre-SAC, and associated AEs are mostly mild-to-moderate and transient. However, the reduced CR in heavily infected and AEs in one-fourth of S. mansoni-infected pre-SAC underscores the need for safety and efficacy monitoring, especially in moderate-to-high infection settings. Integrating pre-SACs in the national deworming programs is recommended to accelerate the elimination of schistosomiasis as a public health problem.

Prevalence and Determinants of Schistosoma mansoni Infection among Pre-School Age Children in Southern Ethiopia.

School-based deworming program is implemented to control and eliminate Schistosoma mansoni infection in many endemic countries, including Ethiopia. However, pre-school-age children (pre-SAC) are not targeted to receive preventive chemotherapy against S. mansoni infection, partly due to a lack of information on the disease burden. We assessed the prevalence and correlates of S. mansoni infection among pre-SAC in Southern Ethiopia. A total of 1683 pre-SAC aged 4 to 7 years were screened for S. mansoni infection. A multilevel binary logistic regression was fitted to detect the significant determinants of S. mansoni infection. Adjusted odds ratios (AORs) with a 95% confidence interval (CI) were used to identify determinants of S. mansoni infection. The overall prevalence of S. mansoni infection was 14.3% (95% CI: 12.6, 16.0%). S. mansoni infection was significantly higher among 6-year-old (AOR = 2.58, 95% CI: 1.55, 4.27) and 7-year-old children (AOR = 4.63, 95% CI: 2.82, 7.62). Accompanying others to water sources sometimes (AOR = 2.60, 95% CI: 1.12, 6.01) and all the time (AOR = 5.91, 95% CI: 2.51, 13.90), and residing in less than one kilometer from the infested water source (AOR = 3.17, 95% CI: 1.47, 6.83) increased the odds of S. mansoni infection. In conclusion, the prevalence of S. mansoni infection among pre-SAC in the study area was moderate. The study highlights the urgent need to include pre-SAC aged 4 to 7 years in annual preventive chemotherapy campaigns to reduce the risk of possible sources of infection and enhance the achievement of the elimination target.

Evaluation of the Antioxidant and Wound Healing Properties of 80% Methanol Extract and Solvent Fractions of the Leaves of Vernonia auriculifera Hiern. (Asteraceae).

Background: The leaves of Vernonia auriculifera (Asteraceae) have traditionally been used to treat wounds in several regions of Ethiopia. The purpose of this study was to assess the wound healing properties of the leaf extract and solvent fractions of V. auriculifera in mice. The leaf extract and solvent fractions of V. auriculifera have also been evaluated for their anti-oxidant properties because of their impact on the wound healing process. Material and Methods: Air-dried leaves were extracted using 80% methanol. They were also successively fractionated with n-hexane, ethyl acetate, and methanol. The residue was then macerated in water for 72 hr. Simple ointment bases were formulated according to British Pharmacopoeia. Thereafter, two types of ointment formulations, 2.5% w/w and 5% w/w, were formulated. Wound healing and acute dermal toxicity studies were performed on mice. To assess free radical scavenging activity, a 2,2-diphenyl-2-picrylhydrazyl free radical (DPPH) assay was performed. Results: In both models, wounds treated with 2.5% and 5% (w/w) of the ME, the aqueous fraction (AQF), methanol fraction (MEF), and ethyl acetate fraction (EAF) ointments demonstrated significant wound healing activity, as shown by enhanced wound contraction, a shortened epithelialization time, increased hydroxyproline content, and enhanced tissue breaking strength. The extract and solvent fractions displayed free radical scavenging activity with IC50 values of 1.2 mg/mL, 1.46 mg/mL, 1.5 mg/mL, and 2.83 mg/mL for ME, AQF, MEF, and EAF, respectively, as compared to 1.42 mg/mL for ascorbic acid. Conclusion: The result of this study indicates that 80% of methanol extract and solvent fractions are endowed with wound healing activity. Additionally, this study has also revealed that ME, AQF, MEF, and EAF have the capacity to scavenge free radicals. The study indicated that the wound healing effect could be attributed to the anti-inflammatory and antioxidant activities.

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract and Solvent Fractions of the Leaves of Vernonia auriculifera Hiern. (Asteraceae).

Background: The leaves of V. auriculifera has been used traditionally for the treatment of inflammatory disorders, and pain in various parts of Ethiopia. However, to our knowledge, the analgesic and anti-inflammatory activity of the crude extract and solvent fractions has never been experimentally studied. Objective: To assess the analgesic and anti-inflammatory activities of V. auriculifera leaf extract and solvent fractions in rodent models. Material and methods: Air-dried leaves of V. auriculifera were grounded and macerated using 80% methanol. The air-dried, grounded leaves were also successively extracted with ethyl acetate, and methanol. The residue was then macerated in water for 72 hr. The extract's peripheral analgesic activity, as well as the solvent fractions, were determined using an acetic acid-induced writhing test. The hot plate model was used to assess the central analgesic effect. Carrageenan-induced hind paw edema and cotton pellet-induced granuloma models were used to assess the anti-inflammatory effect in rats. Results: The 80% methanol leaf extract and solvent fractions have demonstrated significant (p < 0.05) peripheral and central analgesic activity. Both 80% methanol leaf extract and solvent fractions of V. auriculifera were found to have anti-inflammatory activity in a carrageenan-induced rat paw edema model. In the cotton pellet-induced granuloma model, all concentrations of 80% methanol leaf extract (ME), methanol fraction (MEF), and aqueous fractions (AQF) of V. auriculifera inhibited exudate and granuloma formation. Although all tested doses significantly inhibited granuloma mass formation, only the medium and highest ethyl acetate fraction (EAF) doses significantly inhibited the generation of inflammatory exudate. Conclusion: This study's findings indicate that the solvent fractions and 80% methanol extract of V. auriculifera have analgesic and anti-inflammatory properties. This study's findings not only confirm the plants' traditional claim but also provide clues for further investigation of the active principles of this plant for the development of effective and safe analgesic and anti-inflammatory drugs.

Safety and therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria at Shecha health centre, Arba Minch, Ethiopia.

BACKGROUND: In 2004, Ethiopia adopted artemether-lumefantrine (AL, Coartem®) as first-line treatment for the management of uncomplicated Plasmodium falciparum malaria. Continuous monitoring of AL therapeutic efficacy is crucial in Ethiopia, as per the World Health Organization (WHO) recommendation. This study aimed to assess the therapeutic efficacy of AL in the treatment of uncomplicated P. falciparum infection. METHODS: A 28 day onearm, prospective evaluation of the clinical and parasitological response to AL was conducted at Shecha Health Centre, Arba Minch town, Southern Ethiopia. Patients were treated with six-dose regimen of AL over three days and monitored for 28 days with clinical and laboratory assessments. Participant recruitment and outcome classification was done in accordance with the 2009 WHO methods for surveillance of anti-malarial drug efficacy guidelines. RESULTS: A total of 88 study participants were enrolled and 69 of them completed the study with adequate clinical and parasitological response. Two late parasitological failures were observed, of which one was classified as a recrudescence by polymerase chain reaction (PCR). The PCRcorrected cure rate was 98.6% (95% CI 92.3-100). AL demonstrated a rapid parasite and fever clearance with no parasitaemia on day 2 and febrile cases on day 3. Gametocyte clearance was complete by day three. No serious adverse events were reported during the 28 days follow-up. CONCLUSION: The study demonstrated high therapeutic efficacy and good safety profile of AL. This suggests the continuation of AL as the first-line drug for the treatment of uncomplicated P. falciparum malaria in Ethiopia. Periodic therapeutic efficacy studies and monitoring of markers of resistance are recommended for early detection of resistant parasites.

Evaluation of Wound Healing and Antibacterial Activities of Solvent Fractions of 80% Methanol Leaf Extract of Brucea antidysenterica J.F. Mill (Simaroubaceae).

Background: Brucea antidysenterica is a well-known medicinal plant that has traditionally been used to treat a variety of ailments, including wound healing. Supporting the traditional claims, wound healing, antibacterial, anti-inflammatory, and antioxidant activities of the crude extracts of different parts of the plant were reported. The aim of this study was to evaluate the wound healing and antibacterial activities of solvent fractions of the menthol leaf extract of Brucea antidysenterica. Methods: Methanol (80%) leaf extract of Brucea antidysenterica was fractionated using three solvents; water, n-butanol and chloroform. An ointment containing 2% and 4% of each fraction was formulated and applied to wounds inflicted on rats topically. The wound contraction rate, period of epithelialization, and breaking strength were analysed. In vitro antibacterial activities were tested using the agar diffusion method. The macro-tube dilution technique was used to determine the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC) was determined by sub-culturing the MIC and concentrations below the MIC. Results: The 2% and 4% aqueous fractions (AF) significantly increased wound contraction (p 0.001) compared to the negative control and increased tensile strength compared to untreated (p 0.001). Among the three fractions, the n-butanol fraction showed the highest antibacterial growth inhibition, ranging from 8 mm (E. coli) to 16 mm (S. aureus). Conclusion: Data obtained from this study collectively indicated that the aqueous fraction of 80% methanol leaf extract of B. antidysenterica possesses wound healing and antibacterial activities.

Antitrypanosomal Effect of Hydromethanolic Extract of Solanum anguivi Lam on Field Isolates of Trypanosoma congolense Infected Mice.

INTRODUCTION: Trypanosomiasis is one of the world's most serious infectious diseases caused by Trypanosoma parasites. Concern about resistance to conventional antitrypanosomal drugs, mosquito vector resistance to existing insecticide side effects of existing antitrypanosomal drugs justifies the urgent need for more effective, tolerable, and affordable drugs. OBJECTIVE: The present study is aimed at determining the in vivo antitrypanosomal effect of the hydromethanolic extracts of Solanum anguivi fruit extracts against the field isolates of T. congolense. METHODS: The 80% methanol extracts of S. anguivi fruits were prepared by cold maceration technique. In vivo curative tests were done to check the effect of plant extract against T. congolense in Swiss albino mice. Plant extracts were administered at doses of 100, 200, and 400 mg/kg/body weight. Acute toxicity of the extracts at 2000 mg/kg was performed according to OECD guidelines. Data obtained from the experiment were analyzed using one-way ANOVA followed by Tukey test. RESULTS: This study indicated that extract did not exhibit any sign of acute toxicity up to 2000 mg/kg/body weight. In curative test, extracts reduced parasitemia, preventing the drop in packed cell volume and body weight significantly (p < 0.05), compared to control. Groups provided with the extract before infection got prolonged incubation period with chemoprophylactic effect at the doses of 100, 200, and 400 mg/kg. Phytochemical analysis showed presence of flavonoids, steroids, triterpens, saponins, glycosides, tannins, and alkaloids. CONCLUSION: The extract showed promising curative. Further effort is required to isolate and purify specific compounds responsible for antitrypanosomal activity of studied plant.

In Vitro and In Vivo Antitrypanosomal Activities of Methanol Extract of Echinops kebericho Roots.

Microbial resistance to the few conventional antitrypanosomal drugs, increasing resistance of vectors to insecticides, lack of effective vaccines, and adverse effects of the existing antitrypanosomal drugs justify the urgent need for effective, tolerable, and affordable drugs. We assessed antitrypanosomal effects of the hydromethanolic extract of Echinops kebericho Mesfin roots against Trypanosoma congolense field isolate using in vitro and in vivo techniques. Parasite load, packed cell volume (PCV), body weight, and rectal temperature in Swiss albino mice were assessed. This finding is part of the outcomes of drug discovery research for neglected tropical diseases. The extract arrested the motility of trypanosomes within 40 min at 4 and 2 mg/mL concentration, whereas in the untreated control, motility continued for more than 160 min. The extract also reduced parasitemia and prevented drop in PCV and body weight significantly (p < 0.05), as compared to control. Phytochemical analysis showed the presence of flavonoids, triterpenes, steroids, saponins, glycosides, tannins, and alkaloids. It is observed that this extract has activity against the parasite. Isolation and purification of specific compounds are required to identify hit compounds responsible for the antitrypanosomal activity of the studied medicinal plant.

Molecular and Immunological Diagnostic Techniques of Medical Viruses.

Viral infections are causing serious problems in human population worldwide. The recent outbreak of coronavirus disease 2019 caused by SARS-CoV-2 is a perfect example how viral infection could pose a great threat to global public health and economic sectors. Therefore, the first step in combating viral pathogens is to get a timely and accurate diagnosis. Early and accurate detection of the viral presence in patient sample is crucial for appropriate treatment, control, and prevention of epidemics. Here, we summarize some of the molecular and immunological diagnostic approaches available for the detection of viral infections of humans. Molecular diagnostic techniques provide rapid viral detection in patient sample. They are also relatively inexpensive and highly sensitive and specific diagnostic methods. Immunological-based techniques have been extensively utilized for the detection and epidemiological studies of human viral infections. They can detect antiviral antibodies or viral antigens in clinical samples. There are several commercially available molecular and immunological diagnostic kits that facilitate the use of these methods in the majority of clinical laboratories worldwide. In developing countries including Ethiopia where most of viral infections are endemic, exposure to improved or new methods is highly limited as these methods are very costly to use and also require technical skills. Since researchers and clinicians in all corners of the globe are working hard, it is hoped that in the near future, they will develop good quality tests that can be accessible in low-income countries.

Schistosoma mansoni infection among preschool age children attending Erer Health Center, Ethiopia and the response rate to praziquantel.

OBJECTIVE: Preschool age children (PSAC) are excluded from community based praziquantel treatment programs mainly due to paucity of evidence on the magnitude of schistosomiasis, efficacy and safety of this treatment in PSAC. The aim of this study is to assess Schistosoma mansoni infection rate and evaluate response to praziquantel in PSAC. A facility based longitudinal study was employed from April to June 2016 at Erer Health Center, Eastern Ethiopia. Stool sample was examined for schistosomiasis in 236 PSAC and repeated after 4 weeks post-treatment in positive individuals. Treatment outcomes were recorded and interpreted. RESULTS: Out of the 236 study participants, 59 (25%) were infected with S. mansoni. Praziquantel treatment (40 mg/kg) resulted in 96.4% cure rate and 99.4% egg reduction rate. Children of 3-5 year old were significantly affected with S. mansoni infection. Nausea and fatigue were common mild adverse events within 4 h of treatment however moderate and severe adverse events and allergic reactions were not observed. In conclusion, praziquantel at 40 mg/kg, the dose utilized in standard care for school age children, is tolerable and efficacious in the treatment of S. mansoni infection in PSAC, which calls for the healthcare system to provide appropriate service for this population.

In vitro and ex vivo activity of an Azadirachta indica A.Juss. seed kernel extract on early sporogonic development of Plasmodium in comparison with azadirachtin A, its most abundant constituent.

BACKGROUND: NeemAzal® (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. NA contains several azadirachtins (A to L), azadirachtin A (AzaA) being its main constituent. AzaA has been shown to inhibit microgamete formation of the rodent malaria parasite Plasmodium berghei, and NA was found to completely inhibit the transmission of Plasmodium berghei to Anopheles stephensi mosquitoes when administered to gametocytemic mice at a corresponding AzaA dose of 50mg/kg before exposure to mosquitoes. PURPOSE: The present study was aimed at i) assessing the pharmacodynamics and duration of action of NA and AzaA against P. berghei exflagellation in systemic circulation in mice and ii) elucidating the transmission blocking activity (TBA) of the main NA constituents. STUDY DESIGN: The NA and AzaA pharmacodynamics on exflagellation were assessed through ex vivo exflagellation assays, while TBA of NA constituents was evaluated through in vitro ookinete development assay. METHODS: Pharmacodynamics experiments: Peripheral blood from P. berghei infected BALB/c mice with circulating mature gametocytes, were treated i.p. with 50mg/kg and 100mg/kg pure AzaA and with NeemAzal® (Trifolio-M GmbH) at the corresponding AzaA concentrations. The effect magnitude and duration of action of compounds was estimated by counting exflagellation centers, formed by microgametocytes in process of releasing flagellated gametes, at various time points after treatment in ex vivo exflagellation tests. Ookinete Development Assay: The direct effects of NeemAzal® and AzaA on ookinete development were measured by fluorescence microscopy after incubation of gametocytemic blood with various concentrations of test substances in microplates for 24h. RESULTS: The exflagellation tests revealed an half-life of NA anti-plasmodial compounds of up to 7h at a NA dose corresponding to 100mg/kg equivalent dose of AzaA. The ookinete development assay showed an increased activity of NA against early sporogonic stages compared to that of AzaA. The IC50 value determined for NA was 6.8µg/ml (CI95: 5.95-7.86), about half of the AzaA IC50 (12.4µg/ml; CI95: 11.0-14.04). CONCLUSION: The stronger activity of NA, when compared to AzaA, could not be explained by an additive or synergistic effect by other azadirachtins (B, D and I) present in NA. In fact, the addition of these compounds at 50µM concentration to AzaA did not evidence any decrease of the IC50 against early sporogonic stages to that obtained with AzaA alone. It is likely that other non-limonoid compounds present in NA may contribute to AzaA activity and enhanced pharmacodynamics against exflagellation both in vitro and in vivo.

Blocking malaria transmission to Anopheles mosquitoes using artemisinin derivatives and primaquine: a systematic review and meta-analysis.

BACKGROUND: Among the currently used drugs in malaria case management, artemisinin derivatives and primaquine have an impact on the transmissible stages of Plasmodium falciparum. Hence, they reduce the transmission of the parasite from the patient to the mosquitoes. The present study aimed to assess evidence for this hypothesis from controlled trials. METHODS: All controlled clinical trials evaluating the transmission blocking activity of artemisinin derivatives and primaquine with or without other antimalarials were included in this systematic review. PubMed, Google Scholar, Web of Science, ScienceDirect, Medscape and the Cochrane library were systematically searched without language, publication status or date restrictions. The literature references were also scanned manually. The last search was run on July 15, 2013. Search terms included artemisinin derivatives, primaquine, malaria transmission, transmission blocking/reducing drugs and mosquito infection. The outcome measure was the mosquito infectivity rate after treatment of patients. Data were compared using odds ratio (OR), in random effects models. RESULTS: Nine trials with a total of 13,831 mosquitoes were included in the meta-analysis. After combining the trials, the transmission of P. falciparum to Anopheles mosquitoes were lower in artesunate, artemether-lumefantrine and primaquine groups as compared with their control counterparts with OR of 0.36 (95% confidence interval (CI), 0.14-0.90), 0.49 (95% CI, 0.31-0.79) and 0.09 (95% CI, 0.01-0.73); respectively. In non-comparative longitudinal studies, the use of a single-dose of primaquine was shown to deter the transmission of malaria briefly. CONCLUSION: Evidence on the transmission blocking effect of artemisinin derivatives and primaquine is conclusive. Trials evaluating the combined impact of artemisinin derivatives and primaquine on malaria transmission is urgently needed.