Plasmodium falciparum transmission in the highlands of Ethiopia is driven by closely related and clonal parasites.

Malaria cases are frequently recorded in the Ethiopian highlands even at altitudes above 2000 m. The epidemiology of malaria in the Ethiopian highlands, and, in particular, the role of importation by human migration from the highly endemic lowlands is not well understood. We sequenced 187 Plasmodium falciparum samples from two sites in the Ethiopian highlands, Gondar (n = 159) and Ziway (n = 28), using a multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug resistance loci. Here, we characterize the parasite population structure and genetic relatedness. We identify moderate parasite diversity (mean HE : 0.54) and low infection complexity (74.9% monoclonal). A significant percentage of infections share microhaplotypes, even across transmission seasons and sites, indicating persistent local transmission. We identify multiple clusters of clonal or near-clonal infections, highlighting high genetic relatedness. Only 6.3% of individuals diagnosed with P. falciparum reported recent travel. Yet, in clonal or near-clonal clusters, infections of travellers were frequently observed first in time, suggesting that parasites may have been imported and then transmitted locally. 31.1% of infections are pfhrp2-deleted and 84.4% pfhrp3-deleted, and 28.7% have pfhrp2/3 double deletions. Parasites with pfhrp2/3 deletions and wild-type parasites are genetically distinct. Mutations associated with resistance to sulphadoxine-pyrimethamine or suggested to reduce sensitivity to lumefantrine are observed at near-fixation. In conclusion, genomic data corroborate local transmission and the importance of intensified control in the Ethiopian highlands.

Marek's disease in chicken farms from Northwest Ethiopia: gross pathology, virus isolation, and molecular characterization.

Marek's disease virus (MDV) is a highly contagious, immunosuppressive, and oncogenic chicken pathogen causing marek's disease (MD). In this outbreak-based study, 70 dual-purpose chickens that originated from poultry farms in Northwest Ethiopia and suspected of MD were sampled for pathological and virological study from January 2020 to June 2020. Clinically, affected chickens showed inappetence, dyspnea, depression, shrunken combs, and paralysis of legs, wings, and neck, and death. Pathologically, single or multiple greyish white to yellow tumor-like nodular lesions of various size were appreciated in visceral organs. In addition, splenomegaly, hepatomegaly, renomegaly, and sciatic nerve enlargement were observed. Twenty-seven (27) pooled clinical samples i.e. 7 pooled spleen samples and 20 pooled feathers samples were aseptically collected. Confluent monolayer of Chicken Embryo Fibroblast cells was inoculated with a suspension of pathological samples. Of this, MDV-suggestive cytopathic effects were recorded in 5 (71.42%) and 17 (85%) pooled spleen and feather samples respectively. Molecular confirmation of pathogenic MDV was conducted using conventional PCR amplifying 318 bp of ICP4 gene of MDV-1, of which, 40.9% (9/22) tested positive. In addition, 5 PCR-positive samples from various farms were sequenced further confirming the identity of MDV. The ICP4 partial gene sequences were submitted to GenBank with the following accession numbers: OP485106, OP485107, OP485108, OP485109, and OP485110. Comparative phylogenetics showed, two of the isolates from the same site, Metema, seem to be clonal complexes forming distinct cluster. The other three isolates, two from Merawi and one from Debretabor, appear to represent distinct genotypes although the isolate from Debretabor is closer to the Metema clonal complex. On the other hand, the isolates from Merawi appeared genetically far related to the rest of the 3 isolates and clustered with Indian MDV strains included in the analysis. This study presented the first molecular evidence of MDV in chicken farms from Northwest Ethiopia. Biosecurity measures should strictly be implemented to hinder the spread of the virus. Nationwide studies on molecular characteristics of MDV isolates, their pathotypes, and estimation of the economic impact associated with the disease may help justify production and use of MD vaccines within the country.

Serological Evidence of Infectious Laryngotracheitis Infection and Associated Risk Factors in Chickens in Northwestern Ethiopia.

Infectious laryngotracheitis (ILT) is a disease of high economic consequence to the poultry sector. Gallid herpesvirus 1 (GaHV-1), a.k.a infectious laryngotracheitis virus (ILTV), under the genus Iltovirus, and the family Herpesviridae, is the agent responsible for the disease. Despite the clinical signs on the field suggestive of ILT, it has long been considered nonexistent and a disease of no concern in Ethiopia. A cross-sectional study was conducted from November 2020 to June 2021 in three selected zones of the Amhara region (Central Gondar, South Gondar, and West Gojjam zones), Ethiopia, with the objective of estimating the seroprevalence of ILTV in chickens and identifying and quantifying associated risk factors. A total of 768 serum samples were collected using multistage cluster sampling and assayed for anti-ILTV antibodies using indirect ELISA. A questionnaire survey was used to identify the potential risk factors. Of the 768 samples, 454 (59.1%, 95% CI: 0.56-0.63) tested positive for anti-ILTV antibodies. Mixed-effect logistic regression analysis of potential risk factors showed that local breeds of chicken were less likely to be seropositive than exotic breeds (OR: 0.38, 95% CI: 0.24-0.61). In addition, factors such as using local feed source (OR: 6.53, 95% CI: 1.77-24.04), rearing chickens extensively (OR: 1.97, 95% CI: 0.78-5.02), mixing of different batches of chicken (OR: 14.51, 95% CI: 3.35-62.77), careless disposal of litter (OR: 1.62, 95% CI: 0.49-4.37), lack of house disinfection (OR: 11.05, 95% CI: 4.09-47.95), lack of farm protective footwear and clothing (OR: 20.85, 95% CI: 5.40-80.45), and careless disposal of dead chicken bodies had all been associated with increased seropositivity to ILTV. Therefore, implementation of biosecurity measures is highly recommended to control and prevent the spread of ILTV. Furthermore, molecular confirmation and characterization of the virus from ILT suggestive cases should be considered to justify the use of ILT vaccines.

Bad to the bone? - Genomic analysis of Enterococcus isolates from diverse environments reveals that most are safe and display potential as food fermentation microorganisms.

Enterococci comprise a group of lactic acid bacteria (LAB) with considerable potential to serve as food fermentation microorganisms. Unfortunately, enterococci have received a lot of negative attention, due to the occurrence of pathogenic and multidrug resistant strains. In this study, we used genomics to select safe candidates among the forty-four studied enterococcal isolates. The genomes of the forty-four strains were fully sequenced and assessed for presence of virulence and antibiotic resistance genes. Nineteen isolates belonging to the species Enterococcus lactis, Enterococcus faecium, Enterococcus durans, and Enterococcus thailandicus, were deemed safe from the genome analysis. The presence of secondary metabolite gene clusters for bacteriocins was assessed, and twelve candidates were found to secrete antimicrobial compounds effective against Listeria monocytogenes isolated from cheese and Staphylococcus aureus. Physiological characterization revealed nineteen industrial potentials; all strains grew well at 42 °C and acidified 1.5 hours faster than their mesophilic counterpart Lactococcus lactis, with which they share metabolism and flavor forming ability. We conclude that a large fraction of the examined enterococci were safe and could serve as excellent food fermentation microorganisms with inherent bioprotective abilities.

Insights into the in-vitro Susceptibility and Drug-Drug Interaction Profiles Against Drug-Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates in Amhara, Ethiopia.

Background: In Ethiopia, tuberculosis (TB) is a major public health problem. The aim of the study was to determine the in vitro susceptibility level of drugs and drug interaction profiles against drug-resistant and susceptible M. tuberculosis clinical isolates. A laboratory-based cross-sectional study was conducted between January 2023 and August 2023. GenoType MTBDRplus v.2.0 was facilitated in genetic mutation detection. Minimum inhibitory concentration (MIC) was determined using resazurin microtitre assay (REMA), while fractional inhibitory concentration index (FICI) using resazurin drug combination microtitre assay (REDCA) for in vitro quantitative susceptibility and drug interaction prediction. Results: Among 32 clinical isolates, a total of 14 (43.8%) RIF, 20 (62.5%) INH, 2 (6.3%) EMB-related resistant and 14 (43.8%) MDR isolates were identified. Five of RIF-resistant isolates (55.6%) carrying rpoB common mutations at codon S450L were associated with high levels of RIF-resistance with MICs of ≥ 2µg/mL, whereas 100% of isolates harboring rpoB substitutions at codons D435V and H445Y were linked with moderate or low-level RIF-resistance in the MIC ranges from 0.5 to 1µg/mL. A proportion of 81.8% of isolates harboring katG S315T mutations were associated with high-level INH resistance (MIC ≥ 1µg/mL), while the 18.2% of isolates with S315T katG mutations and 100% of isolates with inhA C-15T mutations were linked to the low-level of INH resistance with MIC variability from 0.25 to 0.5µg/mL. Our results indicated that most FICIs of the dual drugs INH+RIF and INH+LEV combination for 9 (28.1%) and 4 (12.5%) INH-resistant isolates, respectively, were ≤0.5, whereas triple drugs INH+RIF+EMB, INH+RIF+LEV and INH+EMB+LEV combination for 6 (18.8%), 11 (34.4%) and 8 (25%) INH-resistant isolates were from 0.62 to 0.75, all showed synergistic effect. Conclusion: The study highlights that isolates with rpoB S450L and katG S315T substitutions were associated with high level of RIF and INH resistance. It is concluded that REDCA can quantitatively determine anti-mycobacterial synergy and that LEV being of potential use against INH-resistant isolates including MDR-TB when combined with RIF+INH and INH+EMB.

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.

A digital microscope for the diagnosis of Plasmodium falciparum and Plasmodium vivax, including P. falciparum with hrp2/hrp3 deletion.

Sensitive and accurate malaria diagnosis is required for case management to accelerate control efforts. Diagnosis is particularly challenging where multiple Plasmodium species are endemic, and where P. falciparum hrp2/3 deletions are frequent. The Noul miLab is a fully automated portable digital microscope that prepares a blood film from a droplet of blood, followed by staining and detection of parasites by an algorithm. Infected red blood cells are displayed on the screen of the instrument. Time-to-result is approximately 20 minutes, with less than two minutes hands-on time. We evaluated the miLab among 659 suspected malaria patients in Gondar, Ethiopia, where P. falciparum and P. vivax are endemic, and the frequency of hrp2/3 deletions is high, and 991 patients in Ghana, where P. falciparum transmission is intense. Across both countries combined, the sensitivity of the miLab for P. falciparum was 94.3% at densities >200 parasites/µL by qPCR, and 83% at densities >20 parasites/µL. The miLab was more sensitive than local microscopy, and comparable to RDT. In Ethiopia, the miLab diagnosed 51/52 (98.1%) of P. falciparum infections with hrp2 deletion at densities >20 parasites/µL. Specificity of the miLab was 94.0%. For P. vivax diagnosis in Ethiopia, the sensitivity of the miLab was 97.0% at densities >200 parasites/µL (RDT: 76.8%, microscopy: 67.0%), 93.9% at densities >20 parasites/µL, and specificity was 97.6%. In Ethiopia, where P. falciparum and P. vivax were frequent, the miLab assigned the wrong species to 15/195 mono-infections at densities >20 parasites/µL by qPCR, and identified only 5/18 mixed-species infections correctly. In conclusion, the miLab was more sensitive than microscopy and thus is a valuable addition to the toolkit for malaria diagnosis, particularly for areas with high frequencies of hrp2/3 deletions.

Corrigendum: Angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of ischemic stroke complication among patients with hypertension in the Ethiopian population.

[This corrects the article DOI: 10.3389/fneur.2023.1093993.].

Angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of ischemic stroke complication among patients with hypertension in the Ethiopian population.

Background: Ischemic stroke is a complicated, multifaceted condition brought on by a confluence of vascular, environmental, and genetic variables. The burden of ischemic stroke is currently rising in terms of death, morbidity, and disability worldwide. Genetic variables also play significant roles in the pathophysiology of hypertension and ischemic stroke in addition to the greatest effects of demographic, clinical, and behavioral risk factors. The key functional variation of the ACE gene that has drawn the most interest is the ACE I/D variant. Even though the ACE gene I/D polymorphism has been widely studied, the findings of investigations on the involvement of this polymorphism in ischemic stroke were contradictory and provide conflicting data. The goal of this study was to look into the effect of the ACE gene I/D polymorphism on the risk of ischemic stroke in patients with hypertension. Methods: A hospital-based case-control study was carried out in 36 cases of patients with hypertensive IS and 36 age- and sex-matched healthy controls. Clinical and biochemical parameters were measured to assess the associated risk factors. The DNA was isolated from blood samples, and the ACE I/D genotypes were identified using polymerase chain reaction and analyzed by agarose gel electrophoresis. Results: The ACE-DD genotype (OR = 3.71, 95% CI = 1.02-13.5; P < 0.05) and D allele (OR = 2.07, 95% CI = 1.06-4.03; P < 0.05) were significantly more common in patients than in controls, indicating that it is a risk factor for the development of ischemic stroke in hypertensive individuals. Conclusion: There is a significant correlation between the ACE gene I/D polymorphism and the development of ischemic stroke in patients with a history of hypertension in the Ethiopian population.

Detecting the Frequency of c.5946delT Pathogenic Variant in the BRCA2 Gene and Associated Risk Factors Among Breast Cancer Patients Visiting Felege Hiwot Referral Hospital and University of Gondar Comprehensive Specialized Hospital.

Background: Breast cancer is one of the most common cancers and the leading cause of death for women worldwide, and the problem is currently getting worse. In Ethiopia, it has become one of the most prevalent cancers, with high rates of morbidity and mortality. The BRCA2 gene variant c.5946delT has been linked to a higher risk of developing breast cancer. Objective: The aim of the present study was to detect the presence of the c.5946delT pathogenic variant in the BRCA2 gene and associated risk factors among breast cancer patients visiting FHRH and UoGCSH. Methods: A cross-sectional study was conducted from September 2021 to October 2022. Peripheral blood samples were collected from 100 patients with breast cancer, and gDNA was extracted using the salting-out method as per the protocol provided in the manufacturer's instructions. The BRCA2 gene c.5946delT variant was detected using the PCR-RFLP technique. The data were analyzed using SPSS version 23. P≤ 0.05 was considered statistically significant. Results: In this study, we discovered that 2% of breast cancer patients had a c.5946delT pathogenic variant of the BRCA2 gene. In addition, the results suggested that the c.5946delT pathogenic variant and age at diagnosis were significantly correlated. On the other hand, there was no significant association between inhabitance and family history for the c.5946delT variant. Conclusion: We have found out that breast cancer patients in the study area had the BRCA2 gene variant c.5946delT, which suggests that this pathogenic variant is linked to breast cancer. Hence, assessing gene alterations using the PCR technique is one of the most effective early diagnostic strategies for breast cancer that should be used in hospitals in order to lower mortality.

Characteristics of TB/HIV Co-Infection and Patterns of Multidrug-Resistance Tuberculosis in the Northwest Amhara, Ethiopia.

Background: Multidrug-resistant tuberculosis (MDR-TB) has continued to be a serious public health threat and significantly challenges global TB control and prevention efforts, where the TB/HIV co-infection epidemic makes the situation much worse. The aim of the study was to determine the determinant factors associated with patterns of MDR-TB among pulmonary TB patients in the Northwest Amhara, Ethiopia. Methods: A hospital-based cross-sectional study was conducted from May 2022 to February 2023 in the Northwest Amhara, Ethiopia. Data on the participants' socio-demographics and clinical characteristics were obtained using a pre-tested checklist. Phenotypic susceptibility testing to first-line anti-TB drugs was performed on 180 isolates by automated BD BACTEC MGIT 960 system. Logistic regression analysis was performed to determine the association of risk factors with patterns of MDR-TB. A p-value ≤0.05 was considered statistically significant. Results: The overall proportion of TB with HIV co-infected cases was 19.8% (50/252). Culture positivity was confirmed in 203/252 (80.6%) of sputum samples. Among 168 isolates, the DST showed that 119 (70.8%) isolates were pan-susceptible to all first-line drugs and prevalence of any resistance to first-line drugs was 49,168 (29.2%). Among the resistant isolates, 28 (16.7%) were any mono-resistance and 12 (7.1%) were determined to be resistant to MDR-TB. TB with a previous TB treatment (aOR = 6.73, 95% CI: 1.78-25.47, p = 0.005) and HIV co-infected (aOR = 0.252, 95% CI: 0.73-0.875, p = 0.03) were significantly associated with MDR-TB. Conclusion: Higher prevalence of TB and MDR-TB was examined among TB patients in the study area. In the study, history of previous TB treatment was the strongest risk factor MDR-TB infection followed by TB with HIV co-infected cases. Therefore, there is a need of strengthening TB control and prevention programs to reduce the increase of TB incidence, further emergence and transmission of a public health threat of MDR-TB cases.

Molecular characterization of genetic mutations with fitness loss in pulmonary tuberculosis patients associated with HIV co-infection in Northwest Amhara, Ethiopia.

Objectives: Molecular approaches to identifying resistance-conferring mutations suggest a revolution in the field of tuberculosis. The aim of the study was to determine the association between resistance-conferring mutations with fitness loss in Mycobacterium tuberculosis clinical isolates and HIV co-infection in the Amhara region of Ethiopia. Methods: A laboratory-based cross-sectional study was conducted between September 2022 and June 2023. A line probe assay was performed on 146 culture-positive clinical isolates. Logistic regression analysis was used to measure the strength of the association between the drug-resistance-conferring mutations with fitness loss in M. tuberculosis isolates and tuberculosis/HIV co-infection. A p-value ⩽ 0.05 was considered statistically significant. Results: A total of 11 distinct mutations at four genetic loci among 19 resistant isolates were detected. The frequency of rifampicin, isoniazid, and fluoroquinolones resistance-conferring mutations was identified in 12 (8.2%), 17 (11.6%), and 2 (1.4%) of the isolates, respectively. The most prominent specific mutations were S450L (5/9, 55.6%), S315T (11/11, 100%), C-15T (4/4, 100%), and D94G (1/1, 100%). Double mutations were observed in 10 (52.6%) multidrug-resistant tuberculosis isolates; the most common were detected in both the rpoB and katG genes (8/10, 80.0%). The HIV-co-infected tuberculosis patients carried a higher proportion of low fitness of non-rpoB S450L variants than those tuberculosis patients without HIV (80.0% vs 14.3%) and showed a significant association (cOR = 0.042, 95% CI: 0.002-0.877, p = 0.041), but not with the low fitness of non-katG S315T variants (cOR = 3.00, 95% CI: 0.348-25.870, p = 0.318). Conclusion: This study provides valuable information on the genetic variants with fitness loss associated with HIV co-infection, but requires further whole-genome-based mutation analysis.

Application of structural equation modelling to inform best management strategies for Marek's disease in Amhara region, Ethiopia.

Marek's disease, a highly contagious and an economically significant oncogenic and paralytic viral diseases of poultry, is becoming a serious problem in Ethiopia's poultry sector. The aim of the study was to examine the relationship between risk factors and their contribution to develop risk with the intentions to implement MD control measures in the different chicken production systems of Ethiopia using the SEM framework. A questionnaire was designed based on the framework and each model constructed was measured using a set of rating scale items. Thus, a sample size of 200 farmers from different production systems were chosen for the data collection. From the analysis, Cornbrash's Alpha (coefficient of reliability) based on the average inter-item correlations were evaluated for each parameter. The result showed that when litter management goes up by 1, the number of sick goes down by 37.575, the number of staff goes up by 1, the number of sick goes down by 7.63, litter management goes up by 1, the number of deaths goes down by 2.505, flock size goes up by 1, the number of deaths goes down by 0.007 than the rest of the activities. The result of this structural equation modeling finding indicates that the data fit the model well (χ2 = 0.201, RMSEA = 0.000, CFI = 1.00, TLI = 1.496, Degrees of freedom = 2) and the model was appropriated. In conclusion, flock size, litter management and number of staff activities have more impact on the numbers of sick, drops in egg production and the number of deaths. Therefore, practicing regular awareness creation for producers regarding management techniques is recommended.

PCR for detection of Leishmania donovani from microscopically negative tissue smears of suspected patients in Gondar, Ethiopia.

BACKGROUND: As untreated visceral leishmaniasis (VL) is fatal, reliable diagnostics are pivotal for accurate treatment allocation. The current diagnostic algorithm for VL in Ethiopia, which is based on the rK39 rapid diagnostic test and microscopy of tissue smears, lacks sensitivity. This probably leads to missed cases and patients not receiving treatment. METHODOLOGY: We conducted a retrospective study on stored microscopically negative spleen and bone marrow smears from suspected VL patients collected at the Leishmaniasis Research and Treatment Center (LRTC) in Gondar, northern Ethiopia between June 2019 and November 2020. Sociodemographic, clinical and treatment data were collected and samples were tested by real-time PCR targeting kinetoplast DNA. PRINCIPLE FINDINGS: Among the 191 eligible samples (135 spleen and 56 bone marrow) with a microscopically negative and valid PCR result, 119 (62.3%) were positive by PCR, although Ct values for some were high (median 33.0). Approximately three quarters of these undiagnosed primary VL (77.3%) and relapse (69.6%) patients did not receive antileishmanial treatment. Of the 56 microscopically negative bone marrow samples, 46 (82.1%) were PCR positive, which is considerably higher compared to the microscopically negative spleen samples, for which 73 out of 135 (54.1%) were PCR positive. The odds of being PCR positive were significantly higher for bone marrow aspirates and higher when white blood cell values were lower and splenomegaly (in cm) was more pronounced. CONCLUSIONS: This study demonstrates that a lot of suspected VL patients remain undiagnosed and untreated. This indicates the urgent need for better diagnostics for VL in the East-African region. The outcomes of PCR positive should be closely monitored and treatment should be provided if the patient deteriorates. In resource limited settings, implementation of PCR on bone marrow aspirate smears of patients with low WBC values and splenomegaly could lead to considerable improvements in patient management.

Impact of XPD gene polymorphism on risk of prostate cancer on north Indian population.

Prostate cancer is the second most diagnosed cancer in men next to skin cancer in the developed world. Risk of disease varies most prominently with age, ethnicity, family history, and diet. Genetic polymorphism of some genes has been implicated in increasing the risk. The XPD (Xeroderma pigmentosum group D) gene codes for a DNA helicase involved in transcription and nucleotide excision repair. The aim of this study is to evaluate the effect of XPD 751 Lys/Gln polymorphism on risk of prostate cancer on north Indian patients. Blood sample from 150 prostate cancer patients, 150 from Prostate Hyper Plasia and equal number of samples from healthy control groups was collected from North India. The polymerase chain reaction and restrictive fragment length polymorphism techniques were implemented. Statistically non-significant increase risk of prostate cancer was observed with patients having Gln/Gln genotype (OR 1.62, 95% CI).

DNA repair genes polymorphism (XPG and XRCC1) and association of prostate cancer in a north Indian population.

Prostate cancer is the most commonly diagnosed cancer in men worldwide and is the second leading cause of cancer related mortality. Genetic background may account for the difference in susceptibility of individuals to different diseases and the relationship between genetic polymorphism and some diseases has been extensively studied. There are several common polymorphisms in genes encoding DNA repair enzymes, some of these polymorphisms are reported to result in subtle structural alterations of the repair enzyme and modulation of the repair capacity. The aim of the present study was to analyze the effect of XPG Asp 1104His and XRCC1 Arg309Gln polymorphisms on risk of prostate cancer in north Indian population. Statistically significant increased risk of prostate cancer was observed on individuals that posses His/His genotype of XPG (OR 2.53, 95% CI 0.99-6.56, P = 0.031). In this study 150 prostate cancer diagnosed patients, 150 healthy controls and 150 BPH (benign prostate hyper plasia) were recruited from north Indian population. Moreover, individuals that carried the Gln/Gln genotype of XRCC1 also showed statistically increased risk of prostate cancer (OR 2.06, 95% CI 1.07-4.00, P = 0.033). The Asp/Asp of XPG and Gln/Gln of XRCC1 in combination showed statistically increased risk of prostate cancer in cases (OR 3.29, 95% CI 1.09-10.16, P = 0.032).

Association of interleukin 4 VNTR polymorphism and HIV/AIDS in a north Indian seropositive patients.

Despite different efforts made to intervene with the deadly nature of HIV/AIDS, all attempts remained unsuccessful due to complexity of the viral host interactions. The solution to HIV-1 pandemic is still to come, thus to assist the efforts being made to intervene with the deadly nature of the virus, different factors responsible for the disease burdens have to be looked into a systematic manner. As a result, the present study aimed to find out the association of IL-4 VNTR polymorphism with HIV-1 susceptibility and rate of disease progression. Three hundred cases and an equal number of sex and age matched controls were included for this study. The polymerase chain reaction assay was utilized to genotype IL-4 VNTR. The results of this study showed statistically significant variation among cases and controls in the distribution of the Rp2/Rp2 genotype (OR = 0.36, 95% CI = 0.18-0.69; P value = 0.0014) indicating, thereby, a possibility of reduced risk of HIV-1 susceptibility. Thus, Rp2/Rp2 genotype of the IL-4 might have a role to play in reducing risk of HIV-1 susceptibility among a north Indian population.

Significance of Tumor necrosis factor α-308 (G/A) gene polymorphism in the development of prostate cancer.

Prostate cancer (PCa) is the most common noncutaneous cancer among men, accounting for 10 % of male cancer-related deaths worldwide. The etiology of PCa is largely unknown, although multiple environmental and lifestyle factors such as ultraviolet irradiation, smoking, and diet might increase the risk of the disease. Risk of disease varies most prominently with age, ethnicity, family history, and diet. The multifunctional cytokine tumor necrosis factor alpha (TNF-α) has an important role in the pathogenesis of inflammatory, autoimmune and malignant diseases. In this case control study 150 Prostate cancer patients and 150 age matched benign prostate hyperplasia (BPH) and equal number of healthy control groups were involved. The aim of this study was to analyze the effect of TNF-α-308 (G/A) polymorphism on risk of prostate cancer on north Indian prostate cancer patients. The polymerase chain reaction (PCR) technique was utilized to genotype TNF-α-308 (G/A) polymorphism. The present study showed statistically significant increased risk of prostate cancer among individuals that carried the A allele of TNF-α-308 gene (OR = 1.81, 95 % CI 1.00-3.481, p = 0.03).

Frequency of rpoB, katG, and inhA Gene Polymorphisms Associated with Multidrug-Resistant Mycobacterium tuberculosis Complex Isolates among Ethiopian TB Patients: A Systematic Review.

Tuberculosis (TB) is one of the top 10 causes of mortality and the first killer among infectious diseases of poverty (IDoPs) worldwide. It disproportionately affects on-third of the world's low-income countries including Ethiopia. One of the factors driving the TB epidemic is the global rise of MDR/XDR-TB and their low detection affect the global TB control progress. Recently, the resistance-associated genetic mutations in MTBC known to confer drug resistance have been detected by rapid molecular diagnostic tests and sequencing methods. In this article, the published literature searched by PubMed database from 2010 to 2021 and English language were considered. The aim of this systematic review was to assess the prevalence of the most common rpoB, katG, and inhA gene mutations associated with multidrug resistance in MTBC clinical strains among TB patients in Ethiopia. Though 22 studies met our eligibility criteria, only 6 studies were included in the final analysis. Using the molecular GenoType MTBDRplus and MTBDRsl line probe assay and sequencing procedures, a total of 932 culture-positive MTBC isolates were examined to determine RIF, INH, and MDR-TB resistance patterns along with rpoB, katG, and inhA gene mutation analysis. As a result, among the genotypically tested MTBC isolates, 119 (12.77%), 83 (8.91%), and 73 (7.32%) isolates were INH, RIF, and MDR-TB resistant, respectively. In any RIF-resistant MTBC strains, the most common single point mutations were in codon 531 (S531L) followed by codon 526 (H526Y) of the rpoB gene. Besides, the most common mutations in any INH-resistant MTBC were strains observed at codon 315 (S315T) and WT probe in the katG gene and at codon C15T and WT1 probe in the inhA promoter region. Detection of resistance allele in rpoB, KatG, and inhA genes for RIF and INH could serve as a marker for MDR-TB strains. Tracking the most common S531L, S315T, and C15T mutations in rpoB, katG, and inhA genes among RIF- and INH-resistant isolates would be valuable in TB diagnostics and treatment regimens, and could reduce the development and risk of MDR/XDR-TB drug-resistance patterns.

Synergetic antibacterial activity of Vernonia auriculifera Hiern and Buddleja polystachya Fresen on selected human pathogenic bacteria.

Background: Medicinal plants have been used as traditional treatments for various human diseases for many years and they are still widely practiced throughout the world. Due to the long history of the practice, medicinal plants have become an integral part of the Ethiopian culture. This study aimed to evaluate the antibacterial activities of Vernonia auriculifera Hiern and Buddleja polystachya Fresen leaf extracts and their synergistic effect against some selected human pathogenic bacteria. Methods: Ethanol, methanol, and n-hexane crude extracts of Vernonia auriculifera, Buddleja polystachya, and a mixture of the two-plant respective of each solvent were evaluated against tested pathogenic bacteria using the agar well diffusion method; the inhibition zones were recorded in millimeters. Gentamycin was used as a positive control, while dimethyl sulfoxide served as a negative control. The minimum inhibitory concentration of the plant extracts against test bacteria was evaluated using two-fold broth dilution methods and then Minimum bactericidal concentration was determined by sub-culturing the test dilutions from minimum inhibitory concentration tubes onto fresh Muller Hinton Agar plates incubated at 37 °C for 24 h. Results: Maximum antibacterial inhibition zone was observed on methanol extracts of synergism against S. Typhimurium (ATCC 1333) (31.00 ± 1.73 mm) while, a minimum inhibition zone was observed on methanol extract of Buddleja polystachya, against E. coli (ATCC 35218) (5.67 ± 0.57). Minimum inhibitory concentration and minimum bactericidal concentration values of the crude extracts of Vernonia auriculifera, Buddleja polystachya, and their mixture lies between (3.125%-12.5%) and (6.25%-25%) respectively. The data were analyzed using the SPSS software package version 20 for windows. Conclusion: The present study revealed that ethanol and methanol extracts of Vernonia auriculifera and Buddleja polystachya possess significant inhibitory effects against tested pathogens and the antibacterial activity of both plants leaf extracts was greater than the activity of currently used antibiotics (Gentamycin) against some selected organisms.