The Role of Pharmacogenomics Studies for Precision Medicine Among Ethiopian Patients and Their Clinical Implications: A Scoping Review.

Background: Pharmacogenomics research is currently revolutionizing treatment optimization by discovering molecular markers. Medicines are the cornerstone of treatment for both acute and chronic diseases. Pharmacogenomics associated treatment response varies from 20% to 95%, resulting in from lack of efficacy to serious toxicity. Pharmacogenomics has emerged as a useful tool for therapy optimization and plays a bigger role in clinical care going forward. However, in Africa, in particular in Ethiopia, such studies are scanty and not generalizing. Therefore, the objective of this review was to outline such studies, generating comprehensive evidence and identify studied variants' association with treatment responses in Ethiopian patients. Methods: The Joanna Briggs Institute's updated 2020 methodological guidelines for conducting and guidance for scoping reviews were used. We meticulously adhered to the systemic review reporting items checklist and scoping review meta-analyses extension. Results: Two hundred twenty-nine possibly relevant studies were searched. These include: 64, 54, 21, 48 and 42 from PubMed, Scopus, Google Scholar, EMBASE, and manual search, respectively. Seventy-seven duplicate studies were removed. Thirty-nine papers were rejected with justification, whereas 58 studies were qualified for full-text screening. Finally 19 studies were examined. The primary pharmacogene that was found to have a significant influence on the pharmacokinetics of efavirenz was CYP2B6. Drug-induced liver injury has frequently identified toxicity among studied medications. Conclusion and Future Perspectives: Pharmacogenomics studies in Ethiopian populations are less abundant. The studies conducted focused on infectious diseases, specifically on HAART commonly efavirenz and backbone first-line anti-tuberculosis drugs. There is a high need for further pharmacogenomics research to verify the discrepancies among the studies and for guiding precision medicine. Systematic review and meta-analysis are also recommended for pooled effects of different parameters in pharmacogenomics studies.

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.

In vitro Anti-Leishmanial Activities of Methanol Extract of Brucea antidysenterica J.F. Mill Seeds and Its Solvent Fractions.

Introduction: Leishmaniasis is one of the neglected tropical diseases, threatening lives of about 350 million people globally. Brucea antidysenterica seeds are used for the treatment of cutaneous leishmaniasis in the traditional medicine in Ethiopia. Objective: This study aimed to evaluate Brucea antidysenterica seeds' anti-leishmanial activity in vitro. Methods: The crude (80% methanol) extract of Brucea antidysenterica seeds and its fractions were evaluated for their anti-leishmanial activities against promastigotes and intracellular amastigotes of Leishmania donovani and Leishmania aethiopica, and for their cytotoxic effects against mammalian cells. The quantitative estimations of total phenolic compounds (TPCs), flavonoids (TFCs) and alkaloids (TACs) were determined, spectrophotometrically. Median inhibitory concentration (IC50) and median cytotoxic concentration (CC50) of the extract and its solvent fractions were calculated using GraphPad Prism 9.1.0 computer software. Data was presented as mean ± standard error of the mean (SEM). Results: The crude extract and its hexane, ethyl acetate and butanol fractions showed anti-leishmanial activities, with IC50 values of 4.14-60.12 µg/mL against promastigotes, and 6.16-40.12 µg/mL against amastigotes of both Leishmania species. They showed moderate cytotoxicity against Vero cell lines and peritoneal mice macrophages, with CC50 values of 100-500 µg/mL, but >1600 µg/mL against red blood cells. Selectivity indices ranged from 7.97 to 30.97. The crude extract, and its ethyl acetate and hexane fractions possessed 54.78-127.72 mg of gallic acid equivalent TPC, 18.30-79.21 mg of quercetin equivalent TFC, and 27.62-97.22 mg of atropine equivalent TAC per gram of extracts. Conclusion: The seeds of the plant possessed anti-leishmanial activities against L. aethiopica and L. donovani that might provide a scientific justification for its use in the treatment of leishmaniasis by traditional healers. Future works are recommended to isolate, purify and identify the possible secondary metabolites attributed to the anti-leishmanial activity.

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.

Nanocellulose/Fe3O4/Ag Nanozyme with Robust Peroxidase Activity for Enhanced Antibacterial and Wound Healing Applications.

Peroxidase memetic nanozymes with their free radical-mediated catalytic actions proved as efficacious antibacterial agents for combating bacterial resistance. Herein, nanocellulose (NC) extracted from Eragrostis teff straw was used to prepare NC/Fe3O4/Ag peroxidase nanozyme as an antibacterial and wound healing agent. Characterization of the nanozyme with XRD, FTIR, SEM-EDX, and XPS confirmed the presence of silver NPs and the magnetite phase of iron oxide dispersed on nanocellulose. The peroxidase activity of the prepared nanozyme was examined using TMB and H2O2 as substrates which turned blue in acidic pH (λmax = 652 nm). With a lower Km (0.387 mM), the nanozyme showed a comparable affinity for TMB with that reported for the HRP enzyme. Furthermore, the nanozyme remained efficient over a broader temperature range while maintaining 61.53% of its activity after the fourth cycle. In vitro, antibacterial tests against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacterial strains showed that NC/Fe3O4/Ag exhibits concentration-dependent and enhanced antibacterial effect for Escherichia coli compared to NC and NC-Fe3O4 and negative control. Furthermore, the wound-healing performance of the NC-Fe3O4-Ag nanozyme was investigated in vivo using an animal model (mice). The nanozyme showed 30% higher wound healing performance compared to the control base ointment and is comparable with the commercial nitrofurazone ointment. The results show the potential of the prepared nanozyme for wound-healing purposes.

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.

Predicting Functional Outcome After Decompressive Craniectomy for Malignant Hemispheric Infarction: Clinical and Novel Imaging Factors.

OBJECTIVE: Decompressive craniectomy (DC) is an established optional treatment for malignant hemispheric infarction (MHI). We analyzed relevant clinical factors and computed tomography (CT) measurements in patients with DC for MHI to identify predictors of functional outcome 3-6 months after stroke. METHODS: This study was performed at 2 comprehensive stroke centers. The inclusion criteria required DC for MHI, no additional intraoperative procedures (strokectomy or cerebral ventricular drain placement), and documented functional status 3-6 months after the stroke. We classified functional outcome as acceptable if the modified Rankin Scale score was <5, or as unacceptable if it was 5 or 6 (bedbound and totally dependent on others or death). Multiple logistic regression analyzed relevant clinical factors and multiple perioperative CT measurements to identify predictors of acceptable functional outcome. RESULTS: Of 87 identified consecutive patients, 66 met the inclusion criteria. Acceptable functional outcome occurred in 35 of 66 (53%) patients. Likelihood of acceptable functional outcome decreased significantly with increasing age (OR 0.92, 95% CI 0.82-0.97, P = 0.004) and with increasing post-DC midline brain shift (OR 0.78, 95% CI 0.64-0.96, P = 0.016), and decreased non-significantly with left-sided stroke (OR 0.30, 95% CI 0.08-1.10, P = 0.069) and with increasing craniectomy barrier thickness (OR 0.92, 95% CI 0.85-1.01, P = 0.076). CONCLUSIONS: Patient age and the post-DC midline shift may be useful in prognosticating functional outcome after DC for MHI. Stroke side and craniectomy barrier thickness merit further ideally prospective outcome prediction testing.

In vitro growth inhibitory activity of Medicines for Malaria Venture pathogen box compounds against Leishmania aethiopica.

INTRODUCTION: Leishmania aethiopica (L. aethiopica) is responsible for different forms of cutaneous leishmaniasis (CL) in Ethiopia. Treatment heavily depends on limited drugs, together with drawbacks like toxicity and microbial resistance. The current research aimed to investigate in vitro growth inhibitory activity of Medicines for Malaria Ventures - Pathogen Box (MMV - PB) compounds against L. aethiopica clinical isolate. METHODOLOGY: Four hundred MMV - PB compounds were screened against L. aethiopica using resazurin based colourimetric assay. Compounds with > 70% inhibition were further tested using macrophage based intracellular amastigote assay. Cytotoxic and hemolytic activity of candidate hits were assessed on THP1- cells and sheep red blood cells (RBCs), respectively. In vitro drug interaction study was also conducted for the most potent hit using the combination index method. RESULTS: At the test concentration of 1 µM, twenty-three compounds showed > 50% inhibition of promastigotes parasite growth, of which 11 compounds showed > 70% inhibition. The 50% growth inhibition (IC50) of the 11 compounds was ranged from 0.024 to 0.483 µM in anti-promastigote assay and from 0.064 to 0.899 µM in intracellular amastigote assay. Candidate compounds demonstrated good safety on sheep RBCs and THP-1 cell lines. MMV688415 demonstrated a slight hemolytic activity on sheep RBC (5.3% at 25 µM) and THP-1 cell line (CC20 = 25 µM) while MMV690102 inhibited half of THP-1 cells at 36.5 µM (selectivity index = 478). No synergistic activity was observed from the combinations of MMV690102 and amphotericin B (CI > 1), and MMV690102 and Pentamidine (CI > 1) at lower and higher combination points. CONCLUSION: The present study identified a panel of compounds that can be used as a novel starting point for lead optimization. MMV690102 appears to be the most potent inhibitor against L. aethiopica promastigotes and amastigotes. Future works should investigate the antileishmanial mechanism of action and in vivo antileishmanial activities of identified hits.

Safety and efficacy of high-dose rifampicin in the management of tuberculosis meningitis: Systematic review and meta-analysis.

Background: Mycobacterium tuberculosis (TB) practically affects any part of the body, but when the brain is involved, the consequences are devastating. Tuberculous meningitis (TBM) is the most severe form of drug-susceptible TB, with an estimation of more than 100,000 new cases occurring every year and a high mortality rate globally. The treatment strategy is based on pulmonary TB (PTB) management regimens which consider rifampicin as the backbone. Optimal treatment regimens for PTB may not be the most effective option for TBM due to difference in TB drug penetration across the blood-cerebrospinal fluid barrier, hence the need for other treatment options. This study aims to review the efficacy and safety of higher doses of rifampicin (>10 mg/kg) compared to 10 mg/kg rifampicin as part of standard therapy for the treatment of TBM. Methods: A systematic review and meta-analysis was conducted to assess the efficacy and safety of high-dose rifampicin for TBM. A search was done on PubMed, Google Scholar, and Cochrane library databases without publication date limit to identify studies providing data on the use of high-dose rifampicin for the treatment of TBM. Titles and abstracts were screened for relevance by three reviewers. Two reviewers used a predefined checklist on the inclusion criteria to assess full text for their eligibility in the review. A heterogeneity test was conducted to assess the variations among study outcomes. The risk ratio (RR) with a 95% confidence interval (CI) was calculated as a measure of intervention effect. The study is registered on PROSPERO and the registration number is CRD42020212737. Results: Five Phase 2 trials with a total of 1028 participants were included in this meta-analysis. All the five trials were used to analyze safety data, which found that there was no significant increase in the risk of Grade 3-5 adverse events in high-dose rifampicin (RR = 1.05; 95% CI = 0.95-1.18). Only four of them were included for the analysis of efficacy. The findings indicated that exposure to high-dose rifampicin is not associated with a reduced risk of mortality (RR = 0.95; 95% CI = 0.78-1.16). Conclusions: It can be concluded from this meta-analysis that there is no significant relation of high-dose rifampicin with adverse events and the reduction of mortality in TBM patients. Whether in future optimized TBM treatment regimen will include high-dose rifampicin or not should be determined by a large-scale clinical trial.

Limiting Brain Shift in Malignant Hemispheric Infarction by Decompressive Craniectomy.

OBJECTIVE: Decompressive craniectomy (DC) improves functional outcomes in selected patients with malignant hemispheric infarction (MHI), but variability in the surgical technique and occasional complications may be limiting the effectiveness of this procedure. Our aim was to evaluate predefined perioperative CT measurements for association with post-DC midline brain shift in patients with MHI. METHODS: At two medical centers we identified 87 consecutive patients with MHI and DC between January 2007 and December 2019. We used our previously tested methods to measure the craniectomy surface area, extent of transcalvarial brain herniation, thickness of tissues overlying the craniectomy, diameter of the cerebral ventricle atrium contralateral to the stroke, extension of infarction beyond the craniectomy edges, and the pre and post-DC midline brain shifts. To avoid potential confounding from medical treatments and additional surgical procedures, we excluded patients with the first CT delayed >30 hours post-DC, resection of infarcted brain, or insertion of an external ventricular drain during DC. The primary outcome in multiple linear regression analysis was the postoperative midline brain shift. RESULTS: We analyzed 72 qualified patients. The average midline brain shift decreased from 8.7 mm pre-DC to 5.4 post-DC. The only factors significantly associated with post-DC midline brain shift at the p<0.01 level were preoperative midline shift (coefficient 0.32, standard error 0.10, p=0.002) and extent of transcalvarial brain herniation (coefficient -0.20, standard error 0.05, p <0.001). CONCLUSIONS: In patients with MHI and DC, smaller post-DC midline shift is associated with smaller pre-DC midline brain shift and greater transcalvarial brain herniation. This knowledge may prove helpful in assessing DC candidacy and surgical success. Additional studies to enhance the surgical success of DC are warranted.

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.

N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis.

Oxidative stress is a common feature of tuberculosis (TB), and persons with reduced antioxidants are at more risk of TB. TB patients with relatively severe oxidative stress had also more advanced disease as measured by the Karnofsky performance index. Since adverse effects from anti-TB drugs are also mediated by free radicals, TB patients are prone to side effects, such as hearing loss. In previous articles, researchers appealed for clinical trials aiming at evaluating N-acetyl cysteine (NAC) in attenuating the dreaded hearing loss during multidrug-resistant TB (MDR-TB) treatment. However, before embarking on such trials, considerations of NAC's overall impact on TB treatment are crucial. Unfortunately, such a comprehensive report on NAC is missing in the literature and this manuscript reviews the broader effect of NAC on TB treatment. This paper discusses NAC's effect on mycobacterial clearance, hearing loss, drug-induced liver injury, and its interaction with anti-TB drugs. Based on the evidence accrued to date, NAC appears to have various beneficial effects on TB treatment. However, despite the favorable interaction between NAC and first-line anti-TB drugs, the interaction between the antioxidant and some of the second-line anti-TB drugs needs further investigations.

Leishmania donovani Growth Inhibitors from Pathogen Box Compounds of Medicine for Malaria Venture.

INTRODUCTION: Leishmaniasis is a collective term used to describe various pathological conditions caused by an obligate intracellular protozoan of the genus Leishmania. It is one of the neglected diseases and has been given minimal attention by drug discovery and development stakeholders to narrow the safety and efficacy gaps of the drugs currently used to treat leishmaniasis. The challenge is further exacerbated by the emergence of drug resistance by the parasites. METHODS: Aiming to look for potential anti-leishmanial hits and leads, we screened Medicines for Malaria Venture (MMV) Pathogen Box compounds against clinically isolated Leishmania donovani strain. In this medium-throughput primary screening assay, the compounds were screened against promastigotes, and then against amastigote stages. RESULTS: From the total 400 compounds screened, 35 compounds showed >50% inhibitory activity on promastigotes in the initial screen (1 µM). Out of these compounds, nine showed >70% inhibition, with median inhibitory concentration (IC50) ranging from 12 to 491 nM using the anti-promastigote assay, and from 53 to 704 nM using the intracellular amastigote assay. Identified compounds demonstrated acceptable safety profiles on THP-1 cell lines and sheep red blood cells, and had appropriate physicochemical properties suitable for further drug development. Two compounds (MMV690102 and MMV688262) were identified as leads. The anti-tubercular agent MMV688262 (delamanid) showed a synergistic effect with amphotericin B, indicating the prospect of using this compound for combination therapy. CONCLUSION: The current study indicates the presence of additional hits which may hold promise as starting points for anti-leishmanial drug discovery and in-depth structure-activity relationship studies.