Resistance In Asia Research Articles

Leveraging collaborative research networks against antimicrobial resistance in Asia.

Antimicrobial resistance (AMR) is a global health security threat requiring research collaboration globally and regionally. Despite repeated calls for international research collaboration in Asia, literature analyzing the nature of collaborative AMR research in Asia has been sparse. This study aims to describe the characteristics of the AMR research network in Asia and investigate the factors influencing collaborative tie formation between organizations. We carried out a mixed-methods study by combining social network analysis (SNA) and in-depth interviews. SNA was first conducted on primary data to describe the characteristics of the AMR research network in Asia. Exponential random graph models (ERGMs) were then used to examine the influence of factors such as organization type, country affluence levels, regional proximity and One Health research on collaborative tie formation among organizations. In-depth interviews were conducted with network participants to provide contextual insights to the quantitative data. The results reveal that the research network exhibits a core-periphery structure, where a minority of organizations have a significantly higher number of collaborations with others. The most influential organizations in the network are academic institutions from high-income countries within and outside Asia. The ERGM results demonstrate that organizations prefer to collaborate with others of similar organization types, country-based affluence levels and One Health domains of focus, but also with others across different World Health Organization regions. The qualitative analysis identified three main themes: the challenges that impede collaboration, the central role of academic institutions, and the nature of collaborations across One Health domains, giving rise to important empirical milestones in understanding AMR research in Asia. We thus recommend leveraging academic institutions as "integrators" to bridge differences, increasing funds channelled towards research capacity building to alleviate structural barriers to collaboration, streamlining collaborative mechanisms to overcome cumbersome administrative hurdles, and increasing efforts to establish trust between all organizations.

Genetic and phenotypic characterizations of IncX3 plasmids harboring bla NDM-5 and bla NDM-16b in Japan.

The spread of the gene encoding the NDM-type carbapenemase, bla NDM, poses a serious threat to clinical practice and public health. This gene is usually carried by transferable plasmids, which facilitates its rapid spread among various species of Enterobacterales. Plasmids with the IncX3 replicon play a major role in the spread of bla NDM in Asian countries. In this study, we conducted genomic sequencing and a comparative analysis of the IncX3-type plasmids harboring bla NDM-5 and bla NDM-16b, a single-nucleotide variant of bla NDM-5, isolated in a national antimicrobial-resistant bacterial genomic surveillance in Japan (Japan Antimicrobial Resistant Bacterial Surveillance), which was carried out during 2019-2020. We compared five plasmids harboring bla NDM-5 and one plasmid harboring bla NDM-16b. They were highly identical and differed in several nucleotide substitutions or variations in insertion sequences, although they were carried by different species or genotypes. Notably, bla NDM-16b-carrying pJBBDACG-19-0070 was identical to a plasmid carrying bla NDM-5 except for one nucleotide substitution in the bla NDM gene throughout the 46 kb sequences. Transformants carrying these two plasmids showed comparative resistance to carbapenems, indicating that a substitution on the NDM enzyme (Ala233 to Val) did not affect carbapenem resistance, at least under normal experimental conditions. A database search revealed that several identical plasmids carrying bla NDM-5 were reported from neighboring countries, mainly China, before our surveillance period. Our analysis suggested that the IncX3 plasmid harboring bla NDM-5 is spreading in Japan, and bla NDM-16b emerged from a single nucleotide substitution on the plasmid, with widespread dissemination in Asian countries. IMPORTANCE IncX3 plasmids harboring bla NDM-5 play a major role in the spread of carbapenem resistance in Asia, particularly in China, in clinical and environmental settings. In this study, we present that Enterobacterales isolates carrying IncX3 plasmids harboring bla NDM-5 have been disseminated in Japan, where their identification was previously rare. In addition, bla NDM-16b, a single-nucleotide variant of bla NDM-5, was found to be carried by an identical IncX3 plasmid. A comparative sequence analysis revealed that the bla NDM-16b gene emerged from a single nucleotide substitution on an IncX3 plasmid harboring bla NDM-5. The bla NDM-16b gene did not confer elevated carbapenem resistance compared to bla NDM-5 in our assay using transformants carrying the plasmid harboring either of these genes, although the A233V substitution was reported to confer stability to the enzyme in ion-depleted conditions. Nevertheless, vigilance regarding the emergence of novel variants is required.

Evaluation of the impact before and after the application of an antimicrobial stewardship program at Dong Thap General Hospital, Vietnam, from 2017 to 2021

Vietnam has one of the highest rates of antibiotic resistance in Asia. In 2020, the Vietnam Minister of Health introduced new legislation for the implementation of an antimicrobial stewardship program (ASP). The evidence for the effectiveness of ASP in small hospitals and hospitals located in provinces was limited compared with larger-scale and central city hospitals. Evaluation of the impact before and after the introduction of an antimicrobial stewardship program at Dong Thap General Hospital, from 2017 to 2021. Retrospective data was collected from June 2017 to June 2021. The impact of the ASP on changes in antibiotic use and the clinical outcome associated with the implementation of the ASP was evaluated using autoregressive integrated moving average modelling of controlled interrupted time-series analysis. There was a significant and sustained decrease in antibiotic consumption level (step change) in 2 indicators, DOT/1000PD (129.55; P<0.01) and LOT/1000PD (99.95, P<0.01), immediately after the ASP intervention. There were no statistically significant changes identified in terms of consumption with DDD/1000PD, or in the clinical outcomes. The results showed no statistically significant change in consumption trend (ramps) in all evaluated indicators. No statistically significant changes in consumption levels and trends were observed in the control group. The ASP implemented in Dong Thap General Hospital from 2017 to 2021 showed a considerable influence on antibiotic consumption as indicated by the DOT/1000 PD and LOT/1000 PD during the initial stages. Moreover, controlling antibiotic consumption did not negatively impact patient outcomes.

KNOWLEDGE AND ATTITUDE OF FARMERS TOWARDS ANTIMICROBIAL RESISTANCE IN ASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: Antimicrobial resistance is a severe threat to public and environmental health. The agricultural sector contributes significantly to resistance, where antimicrobials are used as prophylaxis, growth promoters, and for treatment. A series of studies have been conducted to assess farmers' knowledge and attitude levels with varying results, particularly in Asia, one of the world's largest producers of livestock products. Purpose: To review the pooled estimated level of knowledge and attitude towards antimicrobial use and resistance in Asia. Methods: A literature search was conducted according to PRISMA in Scopus, PubMed, Google Scholar, and Embase for studies up to 30 April 2023. Quality was assessed using the Newcastle-Ottawa Scale (NOS) for cross-sectional studies. Outcomes were further categorized into constructs under knowledge and attitude. Random-effect meta-analysis was conducted using STATA 17. Results: 11 studies and 2131 subjects were included with fair to excellent quality. From the meta-analysis, the following knowledge and attitude levels were estimated: definition [55.7% (95%CI: 37.3%-74%)] and cause [60.6% (95%CI: 40.5%-80.6%)] of antimicrobial resistance; the negative impact of antimicrobials [62.6% (95%CI: 16.9%-100.0%)]; use of antimicrobials for treatment [47.8% (95%CI: 6.1%-89. 4%)], prophylaxis [58.5% (95%CI: 28.5%-88.5%)], growth promoter [39% (95%CI: 23.1%-54.9%)]; discontinuation of antimicrobials upon improving conditions [42.5% (95%CI: 15.4%-69.5%)]. Conclusions: Farmers in Asia have moderate knowledge of antimicrobial resistance but still exhibit attitudes that support resistance.

Correlation P2Y12 Genetic Polymorphism As Risk Factor of Clopidogrel Resistance in Indonesian Stroke Patients.

Stroke is one of the highest causes of disability and mortality in several countries worldwide. Secondary prevention is important in the management of stroke. Clopidogrel is widely used in Asia as secondary prevention for ischemic stroke, even though several studies in Western show limited data related to clopidogrel resistance in Asia. This study aims to determine the correlation between P2Y12 genetic polymorphism and clopidogrel resistance in Indonesia. This study was conducted on one-year duration, the subjects were chosen through the consecutive sampling method, all subjects were examined for genetics and resistance to clopidogrel. The data were analyzed through statistical analysis, a bivariate analysis was conducted to determine the correlation between several variables and the resistance variable. This study employed resistance diagnostic methods with VerifyNow. Polymorphism of receptor P2Y12 was tested with the Polymerase Chain Reaction method (PCR) and analysis of restriction fragment length polymorphism (RFLP). The genes tested in this study were G52T and C34T. The number of participants in this study was 112. Examination of gene P2Y12 showed that the majority was homozygote, wild-type C34T allele (67%), and G52T (66.1%). There was no significant correlation between clopidogrel resistance and gene G52T and C34T of P2Y12 (p > 0.05). Hb levels significantly correlated with P2Y12 G52T (p = 0.024). Meanwhile, Fatty Liver significantly correlated with P2Y12 C34T (p = 0.037). Indonesia showed a low clopidogrel resistance rate and a very low C34T and G52T allele P2Y12 gene mutation, meaning that Indonesia had low mutations in the P2Y12. This is the cause of clopidogrel resistance in this study only 15%. Therefore, in a region with less clopidogrel resistance, examination of the P2Y12 gene would not give significant results.

Updating the Insecticide Resistance Status of Aedes aegypti and Aedes albopictus in Asia: A Systematic Review and Meta-Analysis.

Background: Aedes aegypti and Aedes albopictus are two important vectors of several important arboviruses, including the dengue, chikungunya, and Zika viruses. Insecticide application is an important approach to reduce vector abundance during Aedes spp.-borne outbreaks in the absence of effective vaccines and treatments. However, insecticide overuse can result in the development of resistance, and careful monitoring of resistance markers is required. Methods: This meta-analysis and systematic review explored the spatial and temporal patterns of insecticide resistance in Asia from 2000 to 2021. PubMed, Scopus, EbscoHost, and Embase were used to enhance the search capability. The random-effects model was applied for the 94 studies that met our inclusion criteria for qualitative synthesis and meta-analysis. Results: Four major insecticides were studied (malathion, dichlorodiphenyltrichloroethane, permethrin, and deltamethrin). Dichlorodiphenyltrichloroethane resistance rates were high in both Ae. aegypti and Ae. albopictus (68% and 64%, respectively). Conversely, malathion resistance was less prevalent in Ae. aegypti (3%), and deltamethrin resistance was less common in Ae. albopictus (2%). Ae. aegypti displayed consistently high resistance rates (35%) throughout the study period, whereas the rate of insecticide resistance in Ae. albopictus increased from 5% to 12%. The rates of the major kdr mutations F1534C, V1016G, and S989P were 29%, 26%, and 22%, respectively. Conclusions: Insecticide resistance in both Ae. aegypti and Ae. albopictus is widespread in Asia, although the rates vary by country. Continuous monitoring of the resistance markers and modification of the control strategies will be important for preventing unexpected outbreaks. This systematic review and meta-analysis provided up-to-date information on insecticide resistance in dengue-endemic countries in Asia.

From Secret Fashion Shoots to the #100projectors

From Secret Fashion Shoots to the #100projectors

Iconic 21st Century Activist "T-Shirt and Tote-Bag" Combination Is Hard to Miss These Days!

Iconic 21st Century Activist "T-Shirt and Tote-Bag" Combination Is Hard to Miss These Days!

Effect of Combination Songga-Wood-Stem (Strychnos ligustrina Blume) and Antimalaria-ACT on IL-10 Production of Malaria

Malaria is one of the deadliest infectious diseases in the world. Artemisinin-Based-Combination-Therapy (ACT) an antimalaria recommended by WHO, is starting to experience resistance in Asia. Meanwhile the natural-product-immunoprotective and antimalaria-effect may benefice for malaria. Objective of this study was to determine the effect of combination of ethanolic-extract from Songga-wood-stem (EESWS) and ACT on IL-10, a protective-cytokine against malaria-immunopathology. This experimental-study used post-test-only-randomized-controlled-group-design. The thirty-Swiss-webster-mice were grouped into 5 groups. The one-group of healthy-mice (K1), and the four-groups infected with Plasmodium berghei ANKA (PbA) which were untreated-K2-group, ACT-treated-K3-group, EESWS-treated-P1-group, and EESWS-ACT-combination-treated-P2-group. IL-10-level of stimulated-splenocytes-culture was examined by ELISA-method. Data-analysis-used was One-Way-Anova-Welch-test and Post-hoc Games-Howell. P1 and P2-groups had higher IL-10-levels than K1 (p=0.038). Groups of P1 and P2 showed lower IL-10-levels than K3 (p=0.001). IL-10-level of P2-group was not different than P1 (p=0.135). The conclusion is the EEWS or EESWS-ACT-combination-therapy restrains the increase-splenic-IL-10-production above normal value in the healing phase of malaria infection.

Epidemiology and impact of anti-fungal resistance in Asia

Epidemiology and impact of anti-fungal resistance in Asia

Implementation status of antimicrobial stewardship programs in hospitals: A quantitative analysis study in Ho Chi Minh city, Vietnam

Vietnam has one of the highest multi drug resistance in Asia. Although, despite many efforts to implement the Antimicrobial Stewardship Programs (the ASP) since 2016, studies that on the implementation policy are very lacking of this program are limited. For that reason, we conducted this cross-sectional study to analyze the viewpoint of health workers (HWs) on the implementation of the ASP at some hospitals in Ho Chi Minh City (HCMC). An assessment of 234 HWs showed that the implementation of the ASP in HCMC hospitals was above average (62.7/100.0). A barrier to the implementation consisted of the deficiency in finances, guidelines for diagnosis, and specific interventions for some common infections, such as distributing current antibiogram and monitoring rate of Clostridioides difficile infections. These were the widely recognized problems in initially implementing the ASP. Although most HWs are aware of the importance of implementing the ASP (79.1%), the specific assessment has not been recorded clearly due to the numerous neutral responses. Despite the support of the leadership, the implementation still faces many difficulties and limitations, especially in 3rd and 4th class hospitals. Besides, there was a lack of wide dissemination of information on the ASP at each unit. To generalize the status of the ASP implementation, researchers should conduct qualitative and quantitative studies with a larger scale.

Global View of Urinary Tract Drug-Resistant Infections in Pregnant Women: A Systematic Review and Meta-Analysis

Introduction: Urinary tract infection is one of the most common health problems and hazardous factor among pregnant women. Different microorganisms are contributing in the bacteriuria which by emergence of drug resistance among Gram positive and Negative therapeutic option is very limited. This study is aim to assess the global danger of urinary tract drug-resistant infections in pregnant women. Methods: This meta-analysis which was registered by a pre-defined protocol in PROSPRO carried out in accordance with PRISMA guideline. All international databases were search by English MeSH keywords. Results: A total of 48 from 2005 screened studies that fulfilled the inclusion criteria were selected. In total, E.coli, Klebsiella sp., P. aeruginosa, S. aureus detected as the most common pathogens in UTI's. Results of this analysis demonstrated different resistance rate against studied classes of antibiotics. Nitrofurantoin resistance in E.coli, Klebsiella sp., P. aeruginosa and Staphylococcus aureus isolates were estimated 0.22 (95%CI: 0.15 - 0.30), 0.40 (95%CI: 0.26 - 0.54), 0.81 (95%CI: 0.59-0.97), 0.34 (0.11- 0.63) respectively. Subgroups analysis showed highest resistance in E. coli isolates, in Asia and Africa against Cefotaxim and Ampicillin respectively. Highest resistance in Asia and Africa were related to Ampicillin and Cefotaxime in Klebsiella isolates. Conclusion: In summary, increasing resistance rate in UTI related agents is a risk factor that endangers both mother and fetus. Health care providers should consider screening as the radical part of infection control strategies. Due to low resistance rate to Nitrofurantoin, this drug can be a good choice for UTI treatment in pregnancies, but it should use with caution. Funding Statement: The authors stated: No funding. Declaration of Interests: The authors declared: No. Ethics Approval Statement: The study was registered prospectively by a pre-defined protocol (PROSPERO No: CRD42019133729).

Influence of historical use of antibiotics toward antibiotic resistance

A WHO’s Global Surveillance of Antibiotic Resistance showed there is an increase of antimicrobial resistance in Asia between 2013 until 2014. Many studies showed that there is a correlation between prior antibiotic use with antimicrobial resistance case. The primary objective of this study is to analyze the relationship between prior antibiotic use with antimicrobial resistance. İt was a retrospective and descriptive study conducted at Bangil Regional General Hospital. The data collected from the medical record and microbiological test from the patient at the internal ward. Chi-square analysis used for the statistic. This study showed that prior antibiotic use increased 0,399 bigger for antimicrobial resistance rate (p=0,001).

Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda.

The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed Plasmodium falciparum genetic markers associated with drug sensitivity on 3 occasions at ∼6-month intervals in 2016 and 2017 at 10 sites representing a range of epidemiological settings in Uganda. For putative drug transporters, we found continued evolution toward wild-type sequences associated with increased sensitivity to chloroquine. For pfcrt K76T, by 2017 the prevalence of the wild type was >60% at all sites and >90% at 6 sites. For the pfmdr1 N86Y and D1246Y alleles, wild type prevalence ranged from 80 to 100%. We found low prevalence of K13 propeller domain mutations, which are associated with artemisinin resistance in Asia, but one mutation previously identified in northern Uganda, 675V, was seen in 2.0% of samples, including 5.5% of those from the 3 northernmost sites. Amplification of the pfmdr1 and plasmepsin2 genes, associated elsewhere with decreased sensitivity to lumefantrine and piperaquine, respectively, was seen in <1% of samples. For the antifolate targets pfdhfr and pfdhps, 5 mutations previously associated with resistance were very common, and the pfdhfr 164L and pfdhps 581G mutations associated with higher-level resistance were seen at multiple sites, although prevalence did not clearly increase over time. Overall, changes were consistent with the selective pressure of the national treatment regimen, artemether-lumefantrine, with increased sensitivity to chloroquine, and with poor efficacy of antifolates. Strong evidence for resistance to artemisinins was not seen. Continued surveillance of markers that predict antimalarial drug sensitivity is warranted.

The macrosecuritization of antimicrobial resistance in Asia

ABSTRACTThis article has two objectives. Drawing on the framework provided by macrosecuritization, this article first explores global responses to AMR. Secondly, in shifting the analytical lens to Asia, the article then evaluates how successful this process has been in a regional context. Considering the two objectives, two inter-related arguments are proposed. First, even though AMR can be considered a quintessential and successful macrosecuritization case at the global level, within Asia the operationalisation of AMR strategies is limited by power and resource politics within the states. Second, the anthropocentric nature of health security is limited when it comes to address the threat posed by AMR. Overcoming this limitation requires a One Health approach. However, the successful articulation of this approach has proven challenging in Asia where middle-level actors pull away from the process in pursuit of other agendas. As a result, while macrosecuritization provides a useful tool for understanding how AMR and similar health threats are addressed, it is necessary to understand the local realities within which the process is embedded.

Impact of Intermittent Preventive Treatment During Pregnancy on Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Uganda.

In a recent trial of intermittent preventive treatment in pregnancy (IPTp) in Uganda, dihydroartemisinin-piperaquine (DP) was superior to sulfadoxine-pyrimethamine (SP) in preventing maternal and placental malaria. We compared genotypes using sequencing, fluorescent microsphere, and quantitative polymerase chain reaction assays at loci associated with drug resistance in Plasmodium falciparum isolated from subjects receiving DP or SP. Considering aminoquinoline resistance, DP was associated with increased prevalences of mutations at pfmdr1 N86Y, pfmdr1 Y184F, and pfcrt K76T compared to SP (64.6% vs 27.4%, P < .001; 93.9% vs 59.2%, P < .001; and 87.7% vs 75.4%, P = .03, respectively). Increasing plasma piperaquine concentration at the time of parasitemia was associated with increasing pfmdr1 86Y prevalence; no infections with the N86 genotype occurred with piperaquine >2.75 ng/mL. pfkelch13 propeller domain polymorphisms previously associated with artemisinin resistance were not identified. Recently identified markers of piperaquine resistance were uncommon and not associated with DP. Considering antifolate resistance, SP was associated with increased prevalence of a 5-mutation haplotype (pfdhfr 51I, 59R, and 108N; pfdhps 437G and 581G) compared to DP (90.8% vs 60.0%, P = .001). IPTp selected for genotypes associated with decreased sensitivity to treatment regimens, but genotypes associated with clinically relevant DP resistance in Asia have not emerged in Uganda.

Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence

BackgroundManagement of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia...

Absence of association between polymorphisms in the K13 gene and the presence of Plasmodium falciparum parasites at day 3 after treatment with artemisinin derivatives in Senegal.

In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy as first-line treatment for uncomplicated malaria. In addition, intravenous (i.v.) injection of artesunate and artemether has gradually replaced quinine for the treatment of severe malaria. Mutations in the propeller domain of the Kelch 13 gene (K13-propeller, PF3D71343700), such as Y493H, R539T, I543T and C580Y, were recently associated with in vivo and in vitro resistance to artemisinin in Southeast Asia. However, these mutations were not identified in Africa. In total, 181 isolates of Plasmodium falciparum from 161 patients from Dakar, Senegal, were collected between August 2015 and January 2016. The K13-propeller gene of the isolates was sequenced. A search for non-synonymous mutations in the propeller region of K13 was performed in the 181 isolates collected from Dakar from 2015 to 2016. Three synonymous mutations were detected (D464D, C469C and R471R). Of 119 patients treated with i.v. artesunate or intramuscular artemether followed by artemether/lumefantrine, 9 patients were still parasitaemic on Day 3. Parasites from these nine patients were wild-type for K13-propeller. None of the polymorphisms known to be involved in artemisinin resistance in Asia were detected. These results suggest that K13 is not the best predictive marker for artemisinin resistance in Africa. More isolates from clinical failure cases or patients with delayed parasite clearance after treatment with artemisinin derivatives are necessary to identify new molecular markers.

Repression and Resistance in Asia: Introduction

Pankaj Mishra’s phrase “age of anger” captures the current zeitgeist, not just in the United States and Europe but also many other parts of the world, including the East and Southeast Asian countries that are the focus of this section. Anger can be good for progressive causes. One thing that this collection of dispatches on misrule and discontent show clearly is the need to think of the current illiberal tide wreaking havoc at both ends of Eurasia, as well as to consider what happened before votes were cast over Brexit in May and in the U.S. election in November. The following pieces highlight just how widespread the disturbing trends associated with our age of anger are. But progressives will also find rays of hope in these accounts of repression in Asia, which are also full of examples of brave efforts to push back against authoritarian regimes.

Treatment of Helicobacter pylori infection: Where are we now?

Gastric cancer and Helicobacter pylori infection remain a burden in many Asian countries. In the face of rising antibiotic resistance, the eradication rate of standard triple therapy is declining in many Asian countries. We reviewed the updated epidemiology of gastric cancer, prevalence of H. pylori infection, and antibiotic resistance in Asia. We also reviewed the strategies to improve the efficacy of H. pylori eradication therapies, including the use of high dose proton pump inhibitor, four drug therapies (including bismuth quadruple, concomitant, and sequential therapy), susceptibility guided therapy, extending the treatment duration to 14 days, and development of effective rescue therapy. Four drug therapies are usually more effective than triple therapy when given in the same duration, except in areas with concomitantly high metronidazole resistance and low clarithromycin resistance. The efficacies of different four drug regimens appeared to be similar. However, trials from different geographic areas showed contradictory results, indicating that the optimal therapy should be decided according to the local prevalence of antibiotic resistance. We proposed a prediction model to calculate the efficacy of different regimens according to the prevalence of antibiotic resistance. More large randomized trials which provide information on the antibiotic resistance are urgently needed to build a more accurate and reliable model. It is hoped that we will be able to decide the optimal regimens by routine surveillance of antibiotic resistance.