Relationship between Antibiotic Consumption and Resistance: A Systematic Review.

Background: Unreserved use of antibiotics exerted selective pressure on susceptible bacteria, resulting in the survival of resistant strains. Despite this, the relationship between antibiotic resistance (ABR) and antibiotic consumption (ABC) is rarely studied. This systematic review aims to review the relationship between ABC and ABR from 2016 to 2022. Methods: Articles published over 7 years (2016-2022) were searched from December 23 to 31, 2022. The search strategy was developed by using keywords for ABC and ABR. From 3367 articles, 58 eligible articles were included in the final review. Results: The pooled ABC was 948017.9 DPDs and 4108.6 DIDs where over 70% of antibiotics were from the Watch and Reserve category based on the WHO AWaRe classification. The average pooled prevalence of ABR was 38.4%. Enterococcus faecium (59.4%), A. baumannii (52.6%), and P. aeruginosa (48.6%) were the most common antibiotic-resistant bacteria. Cephalosporins (76.8%), penicillin (58.3%), and aminoglycosides (52%) were commonly involved antibiotics in ABR. The positive correlation between ABR and consumption accounted for 311 (81%). The correlation between ABR P. aeruginosa and ABC accounted for 87 (22.7%), followed by 78 (20.3%) and 77 (20.1%) for ABR E. coli and K. pneumoniae with ABCs, respectively. Consumption of carbapenems and fluoroquinolones was most commonly correlated with resistance rates of P. aeruginosa, K. pneumoniae, E. coli, and A. baumannii. Conclusion: There is a positive correlation between ABC and the rate of ABR. The review also revealed a cross-resistance between the consumption of different antibiotics and ABR. Optimizing antibiotic therapy and reducing unnecessary ABC will prevent the emergence and spread of ABR. Thus, advocating the implementation of stewardship programs plays a pivotal role in containing ABR.

Geographical disparities and determinants of infant mortality in Ethiopia: mapping and spatial analysis using EDHS data.

BACKGROUND: Infant mortality remains a public health challenge in Ethiopia. Exploring infant mortality will aid in tracking the progress toward achieving sustainable development goals. OBJECTIVE: The study aimed to explore the geographical variations and associated factors of infant mortality in Ethiopia. METHOD: A total of 11,023 infants from the 2016 Ethiopian Demographic and Health Survey (EDHS) data were extracted and included in the analysis. EDHS used a two-stage cluster sampling design with a census enumeration area as the primary sampling unit and households as the secondary sampling unit. Arc GIS software was used for spatial analysis using clusters for exploring geographical variations in infant mortality. A binary logistic regression was employed using R software to identify the significant determinants of infant mortality. RESULTS: The study revealed that the spatial distribution of infant mortality was non-random in the country. Infants whose mothers not receiving ANC (AOR = 1.45; 95%CI: 1.17, 1.79), not breastfed status (AOR = 3.94; 95%CI: 3.19, 4.81), poor wealth index (AOR = 1.36; 95%CI: 1.04, 1.77), male infants (AOR = 1.59; 95%CI: 1.29, 1.95), birth order of six or above (AOR = 3.11; 95%CI: 2.08, 4.62), small birth size (AOR = 1.27; 95%CI: 1.26, 1.60), birth spacing [(≤ 24 months (AOR = 2.29; 95%CI: 1.79, 2.92), 25-36 months (AOR = 1.16; 95%CI: 1.12, 1.49)], multiple births (AOR = 6.82; 95%CI: 4.76, 10.81), rural residence (AOR = 1.63; 95%CI: 1.05, 2.77) and regions [Afar (AOR = 1.54; 95%CI: 1.01, 2.36), Harari (AOR = 1.56; 95%CI: 1.04, 2.56), and Somali (AOR = 1.52; 95%CI: 1.03, 2.39)] were the determinants of infant death in Ethiopia. CONCLUSIONS: There is a great geographical disparity in infant mortality rates across regions. Afar, Harari, and Somali regions were verified as hot spot areas. ANC usage, breastfed status, wealth index, sex of the infant, birth order, birth size, birth spacing, birth type, residence, and region were the determinants of infant death in Ethiopia. Therefore, appropriate interventions need to be implemented in the hot spots to alleviate the risk factors for infant mortality.

High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND: Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown. METHODS: A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8(+) T cells, STAT4, and INF-γ proteins. RESULTS: STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence. CONCLUSIONS: Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.

Assessment of challenges and opportunities in antibiotic stewardship program implementation in Northwest Ethiopia.

Background: Indiscriminate use of antibiotics leads to antibiotic resistance (AMR) and results in mortality, morbidity, and financial burden. Antibiotic stewardship programs (ASPs) with education can resolve a number of barriers recognized in the implementation of successful ASPs. The aim of this study was to assess health professionals' perceptions and status of ASPs in hospitals in 2022. Methods: A cross-sectional study was conducted from September 1, 2022 to October 30, 2022. A total of 181 health professionals were included, and a self-administered questionnaire was used to collect data. The status of hospitals was assessed using a checklist. The data were analyzed using SPSS version 23, and descriptive statistics and Chi-square tests (X2) at a P-value of <0.05 were used. Results: Of the 181 respondents, 163 (90.1 %), and 161 (89.0 %) believed that AMR is a significant problem in Ethiopia and globally, respectively. Easy access to antibiotics 155 (85.6 %), and inappropriate use 137 (75.7 %) were perceived as key contributors to AMR. Antibiotics were believed to be prescribed/dispensed without laboratory results 86 (47.5 %), and antibiotic susceptibility patterns were not considered to guide empiric therapy 81 (44.8 %). ASP was believed to reduce the duration of hospital stays and associated costs 137 (75.7 %), and improve the quality of patient care 133 (73.5 %), whereas 151 (83.4 %), 143 (79 %), and 142 (78.5 %) suggested education, institutional guidelines, and prospective audits with feedback interventions to combat AMR in their hospitals, respectively. There were significant differences in perception among professionals based on professional category and attempts by hospitals to implement ASPs. Although ASPs were not functioning according to standard, there have been attempts to implement it in three hospitals. The issue of ASP had never been heard in general hospitals. Currently, it is feasible to implement ASPs in four hospitals. Conclusion: The status of ASP in hospitals was very poor. Despite a lack of prior knowledge on ASPs, most respondents do have a positive perception of AMR and the implementation of ASPs. Pharmacist-led prospective audits and feedback with education and institutional guidelines for empiric antibiotic use can be better implemented in hospitals. Involvement of representatives from infection prevention and control, and collaboration among hospitals in ASP implementation will help establish a strong ASP in the area.

A six years trend analysis of systemic antibiotic consumption in Northwest Ethiopia.

BACKGROUND: Consumption of antibiotics, a major global threat to public health, is perhaps the key driver of antibiotic resistance. Monitoring antibiotic consumption is crucial to tackling antimicrobial resistance. This study assessed antibiotic consumption trends during the last six years in the Bahir Dar branch of the Ethiopian pharmaceutical supply agency (EPSA), Northwest Ethiopia, in 2022. METHODS: Retrospective data were collected in August 2022 based on antibiotic distribution data from the Bahir Dar Brach of EPSA from July 2016 to June 2022. Data were analyzed according to the Anatomic Therapeutic Classification (ATC) developed by the World Health Organization (WHO). We measured antibiotic consumption using a defined daily dose per 1000 inhabitants per day (DIDs) based on the Agency's catchment population. Descriptive statistics and trend analyses were conducted. RESULTS: About 30.34 DIDs of antibiotics were consumed during the six years. The consumption of antibiotics decreased by 87.4%, from 6.9 DIDs in 2016/17 to 0.9 DIDs in 2021/22. Based on the WHO AWaRe classification, 23.39 DIDs (77.1%) of the consumed antibiotics were from the Access category. Consumption of Access category antibiotics was decreased by 72.7% (from 5 to 0.5 DIDs) but Watch antibiotics decreased by 54.3% (from 1.8 to 0.4 DIDs). Oral antibiotics accounted for 29.19 DIDs (96.2%) of all consumed systemic antibiotics. The average cost expenditure per DDD for all antibiotics was 54.1 birr/DDD (0.4-482.3 birr/DDD). Only seven antibiotics accounted for DU90% and the cost expenditure per DDD for the DU90% antibiotics ranged from 0.4/DDD for Doxycycline to 232.8 birr/DDD for Piperacillin/tazobactam. Overall, during the last six years, the most commonly used antibiotic was Amoxicillin (10.1 DIDs), followed by Doxycycline (5.3 DIDs) and Ciprofloxacin (3.4 DIDs). CONCLUSION: In this study, we found that antibiotic usage was low and continuously declining over time. Minimizing unnecessary antibiotic usage is one possible approach to reduced AMR. However, a shortage of access to important medicines can compromise the quality of treatment and patient outcomes. A prospective study is needed to evaluate the balance of patient outcomes and reduce AMR by optimizing the community consumption of systemic antibiotics.

Genetic diversity of Mycobacterium tuberculosis strains isolated from spiritual holy water site attendees in Northwest Ethiopia. A cross-sectional study.

Background: The genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia. Methods: A cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the Löwenstein-Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect first-and second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15. Results: Of 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East-African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%.Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance. Conclusions: Diverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.

Spiritual Holy Water Sites in Ethiopia: Unrecognized High-Risk Settings for Transmission of Pulmonary Tuberculosis.

Ethiopia is a high-tuberculosis (TB) burden country with 157 new cases per 100,000 people, with 23,800 TB-related deaths in 2020. In Ethiopia, TB patients have different healthcare-seeking behaviors. They frequently visit spiritual places, such as holy water sites (HWSs), to seek treatment for their illness spiritually. This study examined the prevalence of pulmonary TB (PTB) and drug susceptibility profiles of Mycobacterium tuberculosis (MTB) isolates among spiritual HWS attendees in Northwest Ethiopia. A cross-sectional study was conducted from June 2019 to March 2020. Sputum samples were collected, processed, and cultured using Löwenstein-Jensen (LJ) culture medium. Second-generation line probe assays (LPAs), GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0, were used to detect anti-TB drug-resistant isolates. STATA 17 was utilized to perform descriptive statistics, bivariate, and multivariate regression analyses. Of 560 PTB-symptomatic participants, 21.8% ((95% confidence interval (95 CI): 18.4-25.2%)) were culture-positive, resulting in a point prevalence of 1,183/100,000 attendees. Amongst HWS attendees, culture-positive TB occurred most commonly in persons 18-33 years of age (28.5% (95 CI 23.4-34.3%)). Other participant characteristics significantly associated with culture-positive PTB were as follows: rural residents (adjusted odds ratio (aOR) 2.65; 95 CI 1.38-5.10), married participants (aOR 2.43; 95 CI 1.28-4.63), family members >5 per household (aOR 1.84; 95 CI 1.04-3.24), and sharing living space (aOR 10.57; 95 CI 3.60-31.13). Also, among 438 participants followed for 12 months after showing negative TB culture results while at the HWS, 6.8% (95 CI 4.4-9.4%) developed or contracted culture-positive TB post-residency at the HWSs. Of the 122 tested isolates, 20 (16.4%) were isoniazid (INH) and/or rifampicin (RIF) resistant. Multidrug-resistant (MDR) TB was detected in 15 cases (12.3%), five of which were fluoroquinolones (FLQs) resistant. The findings from this study should raise a concern about HWSs as potential high-risk settings for TB transmission. It is recommended that appropriate control measures be instituted that include compulsory TB testing and tightened infection control at HWSs, where an increased risk exists for transmission of TB.

Gender-based violence in the context of armed conflict in Northern Ethiopia.

BACKGROUND: Gender-based violence (GBV) particularly against women is unfortunately common during armed conflicts. No rigorous and comprehensive empirical work has documented the extent of GBV and its consequences that took place during the two years of devastating armed conflict in Northern Ethiopia. This study aims to assess GBV and its consequences in war-torn areas of northern Ethiopia. METHODS: We used a qualitative method augmented by quantitative method to enroll research participants. We conducted in-depth interviews to characterize the lived experiences of GBV survivors. All interviews were conducted confidentially. The data were collected to the point of data saturation. All interviews were transcribed verbatim into local language, translated into English, and analyzed using a thematic analysis approach. We also used reports from healthcare facilities and conducted a descriptive analysis of the demographic characteristics of study participants. RESULTS: One thousand one hundred seventy-seven persons reported GBV to healthcare providers. The qualitative study identified several forms of violence (sexual, physical, and psychological). Gang rape against women including minors as young as 14 years old girls was reported. Additionally, the perpetrators sexually violated women who were pregnant, and elderly women as old as 65 years, who took refuge in religious institutions. The perpetrators committed direct assaults on the body with items (e.g., burning the body with cigarette fire) or weapons, holding women and girls as captives, and deprivation of sleep and food. GBV survivors reported stigma, prejudice, suicide attempts, nightmares, and hopelessness. GBV survivors dealt with the traumatic stress by outmigration (leaving their residences), seeking care at healthcare facilities, self-isolation, being silent, dropping out of school, and seeking counseling. CONCLUSION: GBV survivors were subjected to multiple and compounding types of violence, with a wide range of adverse health consequences for survivors and their families. GBV survivors require multifaceted interventions including psychological, health, and economic support to rehabilitate them to lead a productive life.

Prevalence of Leishmania RNA virus in Leishmania parasites in patients with tegumentary leishmaniasis: A systematic review and meta-analysis.

BACKGROUND: Cutaneous leishmaniasis is caused by different protozoan parasites of the genus Leishmania. Leishmania RNA virus (LRV) was identified as the first Leishmania infecting virus in 1998. Different studies showed the presence and role of the LRV in Leishmania parasites causing cutaneous leishmaniasis (CL). However, there is limited data on the pooled prevalence of LRV in Leishmania parasites causing CL. Therefore, the aim of this systematic review and meta-analysis was to determine the pooled prevalence of LRV in Leishmania parasite isolates and/or lesion biopsies in patients with CL from the available literature globally. METHODOLOGY: We retrieved the studies from different electronic databases. The studies were screened and identified based on the inclusion and exclusion criteria. We excluded studies exclusively done in experimental animals and in vitro studies. The review was conducted in line with PRISMA guidelines. The meta-analysis was performed with Stata software version 14 with metan command. The forest plot with random-effect model was used to estimate the pooled prevalence with 95% confidence interval. Inverse variance index (I2) was used to assess the heterogeneity among the included articles. PRINCIPAL FINDINGS: A total of 1215 samples from 25 studies were included. Of these, 40.1% (487/1215) were positive for LRV. The overall pooled prevalence of LRV globally was 37.22% (95% CI: 27.54% - 46.90%). The pooled prevalence of LRV in the New World (NW) and Old World (OW) regions was 34.18% and 45.77%, respectively. Leishmania guyanensis, L. braziliensis, L. major, and L. tropica were the most studied species for the detection of LRV. The prevalence of LRV from Leishmania isolates and lesion biopsies was 42.9% (349/813) and 34.3% (138/402), respectively. CONCLUSION: This systematic study revealed that there is high prevalence of LRV in Leishmania parasites isolated from patients with CL. More comprehensive studies would be required to investigate the presence of the LRV in other Leishmania species such as L. aethiopica to fully understand the role of LRV in different clinical manifestations and disease pathology presented in CL patients.

High NEK2 Expression Is a Predictor of Tumor Recurrence in Hepatocellular Carcinoma Patients After Hepatectomy.

BACKGROUND/AIM: Better prognosis of cancer including hepatocellular carcinoma (HCC) remains unsatisfactory due to recurrence and chemoresistance. In this respect it is important to identify molecular targets specific to the disease in order to design effective therapeutic strategies. In the present study, we investigated the prognostic role of Never-in-mitosis-A-related kinase 2 (NEK2) in HCC. MATERIALS AND METHODS: Fifty HCC patients who underwent hepatectomy were enrolled in the study. NEK2 gene and protein expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. RESULTS: Higher expression of NEK2 was detected in HCC tumoral compared to adjacent non-tumor tissues (p<0.001), and protein expression was also relatively high in tumor than corresponding non-tumor tissues. Furthermore, high NEK2 expression was positively correlated with hepatic venous invasion (p=0.047), des-gammacarboxy prothrombin (p=0.003), and alpha-fetoprotein (AFP) (p=0.024). Patients with high NEK2 expression had significantly poor recurrence-free survival (p=0.042) and early recurrence. CONCLUSION: Overall, these results suggest that NEK2 could be a promising biomarker for HCC recurrence.

Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.

BACKGROUND: Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. MATERIALS AND METHODS: Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. RESULTS: BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). CONCLUSION: BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions.