Decadal Analysis of ESBL-Escherichia coli Antibiotic Resistance Patterns in Urine Samples from Nepal: A Systematic Review and Meta-Analysis

Copyright (c) 2024 Bibek Rana Chhetri, Rajat Thapa, Megha Raj Banjara. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.33314/jnhrc.v21i3.4723This systematic review aimed to determine the antimicrobial resistance pattern of the extended-spectrum β-lactamases producing Escherichia coli (ESBL-EC) in urine samples in Nepal. Systematic literature review was conducted to locate all articles reporting ESBL-EC in urine samples published between January 2012 to December 2022. The Egger's weighted regression analysis was done to assess the publication bias. A random-effects model was used to calculate the pooled prevalence and corresponding 95% confidence interval due to significant between-study heterogeneity. The strength of correlation between multidrug resistance and ESBL production in E.coli strains was determined using Pearson's correlation coefficient. The data were analyzed using R-language 4.2.2. software. The combined prevalence of E.coli in urine samples was found to be 14 % (95% CI, 11-18), while the overall pooled prevalence of ESBL E.coli and MDR E.coli were 30% (95% CI, 20-42) and 70% (95% CI, 38-90) respectively. A strong positive correlation of 0.99 (95% CI, 0.89-1.0) was found between ESBL production and MDR among E.coli isolates. Imipenem was the drug of choice against ESBL-E.coli in urine specimens. Our analyses showed the overall ESBL-EC and MDR-EC burden in Nepal is considerably high. Likewise, the study also infers an increasing trend of antibiotic resistance pattern of ESBL-EC in urine samples

Field assessment of the operating procedures of a semi-quantitative G6PD Biosensor to improve repeatability of routine testing

In remote communities, diagnosis of G6PD deficiency is challenging. We assessed the impact of modified test procedures and delayed testing for the point-of-care diagnostic STANDARD G6PD (SDBiosensor, RoK), and evaluated recommended cut-offs. We tested capillary blood from fingerpricks (Standard Method) and a microtainer (BD, USA; Method 1), venous blood from a vacutainer (BD, USA; Method 2), varied sample application methods (Methods 3), and used micropipettes rather than the test’s single-use pipette (Method 4). Repeatability was assessed by comparing median differences between paired measurements. All methods were tested 20 times under laboratory conditions on three volunteers. The Standard Method and the method with best repeatability were tested in Indonesia and Nepal. In Indonesia 60 participants were tested in duplicate by both methods, in Nepal 120 participants were tested in duplicate by either method. The adjusted male median (AMM) of the Biosensor Standard Method readings was defined as 100% activity. In Indonesia, the difference between paired readings of the Standard and modified methods was compared to assess the impact of delayed testing. In the pilot study repeatability didn’t differ significantly (p = 0.381); Method 3 showed lowest variability. One Nepalese participant had <30% activity, one Indonesian and 10 Nepalese participants had intermediate activity (≥30% to <70% activity). Repeatability didn’t differ significantly in Indonesia (Standard: 0.2U/gHb [IQR: 0.1–0.4]; Method 3: 0.3U/gHb [IQR: 0.1–0.5]; p = 0.425) or Nepal (Standard: 0.4U/gHb [IQR: 0.2–0.6]; Method 3: 0.3U/gHb [IQR: 0.1–0.6]; p = 0.330). Median G6PD measurements by Method 3 were 0.4U/gHb (IQR: -0.2 to 0.7, p = 0.005) higher after a 5-hour delay compared to the Standard Method. The definition of 100% activity by the Standard Method matched the manufacturer-recommended cut-off for 70% activity. We couldn’t improve repeatability. Delays of up to 5 hours didn’t result in a clinically relevant difference in measured G6PD activity. The manufacturer’s recommended cut-off for intermediate deficiency is conservative

The durability of long-lasting insecticidal nets distributed to the households between 2009 and 2013 in Nepal

Background: Understanding and improving the durability of long-lasting insecticidal nets (LLINs) in the field are critical for planning future implementation strategies including behavioral change for care and maintenance. LLIN distribution at high coverage is considered to be one of the adjunctive transmission reduction strategies in Nepal’s Malaria Strategic Plan 2014–2025. The main objective of this study was to assess the durability through assessment of community usage, physical integrity, residual bio-efficacy, and chemical retention in LLINs: Interceptor®, Yorkool®, and PermaNet ®2.0 which were used in Nepal during 2009 through 2013. Methods: Assessments were conducted on random samples (n = 440) of LLINs from the eleven districts representing four ecological zones: Terai plain region (Kailali and Kanchanpur districts), outer Terai fluvial ecosystem (Surkhet, Dang, and Rupandhei districts), inner Terai forest ecosystem (Mahhothari, Dhanusa, and Illam districts), and Hills and river valley (Kavrepalanchock and Sindhupalchok districts). For each LLIN, fabric integrity in terms of proportionate hole index (pHI) and residual bio-efficacy were assessed. However, for chemical retention, a representative sample of 44 nets (15 Yorkool®, 10 Permanet®2.0, and 19 Interceptor®) was evaluated. Data were analyzed using descriptive statistics stratified by LLINs brand, districts, and duration of exposure. Results: On average, duration of use of LLINs was shortest for the Yorkool® samples, followed by PermaNet® 2.0 and Interceptor® with median ages of 8.9 (IQR = 0.4), 23.8 (IQR = 3.2), and 50.1 (IQR = 3.2) months, respectively. Over 80% of field distributed Yorkool® and PermaNet® 2.0 nets were in good condition (pHI< 25) compared to Interceptor® (66%). Bio-efficacy analysis showed that average mortality rates of Interceptor and Yorkool were below World Health Organization (WHO) optimal effectiveness of ≥ 80% compared to 2-year-old PermaNet 2.0 which attained 80%. Chemical retention analysis was consistent with bio-efficacy results. Conclusion: This study shows that distribution of LLINs is effective for malaria control; however, serviceable life of LLINs should be considered in terms of waning residual bio-efficacy that warrants replacement. As an adjunctive malaria control tool, National Malaria Control Program of Nepal can benefit by renewing the distribution of LLINs in an appropriate time frame in addition to utilizing durable and effective LLINs

Visceral Leishmaniasis Clinical Management in Endemic Districts of India, Nepal, and Bangladesh

Background. National VL Elimination Programs in India, Nepal and Bangladesh face challenges as home-based Miltefosine treatment is introduced. Objectives. To study constraints of VL management in endemic districts within context of national elimination programs before and after intervention. Methods. Ninety-two and 41 newly diagnosed VL patients were interviewed for clinical and provider experience in 2009 before and in 2010 after intervention (district training and improved supply of diagnostics and drugs). Providers were assessed for adherence to treatment guidelines. Facilities and doctor-patient consultations were observed to assess quality of care. Results. Miltefosine use increased from 33% to 59% except in Nepal where amphotericin was better available. Incorrect dosage and treatment interruptions were rare. Advice on potential side effects was uncommon but improved significantly in 2010. Physicians did not rule out pregnancy prior to starting Miltefosine. Fever measurement or spleen palpation was infrequently done in Bangladesh but improved after intervention (from 23% to 47%). Physician awareness of renal or liver toxicity as Miltefosine side effects was lower in Bangladesh. Bio-chemical monitoring was uncommon. Patient satisfaction with services remained low for ease of access or time provider spent with patient. Health facilities were better stocked with rK39 kits and Miltefosine in 2010

Options for Active Case Detection of Visceral Leishmaniasis in Endemic Districts of India, Nepal and Bangladesh, Comparing Yield, Feasibility and Costs

For the elimination of any infectious disease (i.e., reduction of the burden of a serious public health problem to a minor problem which can be managed by the general health services) the right mix of public health tools has to be identified for the early detection and successful treatment of new cases as well as effective vector control (in the case of vector borne diseases) at affordable costs. The paper provides a powerful example of evidence building for cost-effective early case detection in the visceral leishmaniasis elimination initiative of Bangladesh, India and Nepal. It compares the camp approach (mobile teams testing in chronic fever camps for spleen enlargement and rapid diagnostic tests) with the index case approach (screening for new cases in the neighbourhood of reported visceral leishmaniasis patients) and the incentive based approach (where basic health workers receive an allowance for detecting a new case) using subsequent house-to-house screening for the identification of the real number of un-detected cases. By applying a mix of different study methods and an itinerate research process to identify the most effective, feasible and affordable case detection method, under different environmental conditions, recommendations could be developed which help governments in shaping their visceral leishmaniasis elimination strategy

Public health responses to a dengue outbreak in a fragile state: a case study of Nepal.

Objectives. The number of countries reporting dengue cases is increasing worldwide. Nepal saw its first dengue outbreak in 2010, with 96% of cases reported in three districts. There are numerous policy challenges to providing an effective public health response system in a fragile state. This paper evaluates the dengue case notification, surveillance, laboratory facilities, intersectoral collaboration, and how government and community services responded to the outbreak. Methods. Qualitative data were collected through 20 in-depth interviews, with key stakeholders, and two focus-group discussions, with seven participants. Results. Limitations of case recognition included weak diagnostic facilities and private hospitals not incorporated into the case reporting system. Research on vectors was weak, with no virological surveillance. Limitations of outbreak response included poor coordination and an inadequate budget. There was good community mobilization and emergency response but no routine vector control. Conclusions. A weak state has limited response capabilities. Disease surveillance and response plans need to be country-specific and consider state response capacity and the level of endemicity. Two feasible solutions for Nepal are (1) go upwards to regional collaboration for disease and vector surveillance, laboratory assistance, and staff training; (2) go downwards to expand upon community mobilisation, ensuring that vector control is anticipatory to outbreaks

Molecular detection of plasmid mediated bla TEM, bla CTX−M,and bla SHV genes in Extended Spectrum β-Lactamase (ESBL) Escherichia coli from clinical samples

Abstract Background Extended spectrum β-lactamases (ESBLs) are a group of beta-lactamase enzymes that confer resistance to the oxyimino-cephalosporins and monobactams. The emergence of ESBL - producing genes possesses a serious threat for treating infections since it is associated with multi-drug resistance. This study was focused to identify the ESBLs producing genes from Escherichia coli isolates from clinical samples from a referral-level tertiary care hospital in Lalitpur. Methods This was a cross-sectional study conducted from September 2018 to April 2020 at the Microbiology Laboratory of Nepal Mediciti Hospital. Clinical samples were processed, and culture isolates were identified and characterized following standard microbiological techniques. An antibiotic susceptibility test was performed by a modified Kirby-Bauer disc diffusion method as recommended by Clinical and Laboratory Standard Institute guidelines.Extended -spectrum beta-lactamases were phenotypically confirmed by the combined disc method. The ESBL-producing genes bla TEM, bla CTX−M and bla SHV were confirmed by PCR. Results Of the 1449 total E. coli isolates, 22.29% (323/1449) isolates were multi-drug resistant (MDR). Among the total MDR E. coli isolates, 66.56% (215/323) were ESBL producers. The maximum number of ESBL E. coli was isolated from urine 90.23% (194) followed by sputum 5.58% (12), swab 2.32% (5), pus 0.93% (2), and blood 0.93% (2). The antibiotic susceptibility pattern of ESBL E. coli producers showed the highest sensitivity toward tigecycline (100%) followed by polymyxin b, colistin and meropenem. Out of 215 phenotypically confirmed ESBL E. coli, only 86.51% (186) isolates were found to be positive by PCR for either bla TEM or bla CTX−M genes. Among the ESBL genotypes, the most common were bla TEM 63.4% (118) followed by bla CTX−M 36.6% (68). Conclusion The emergence of MDR and ESBL – producing E. coli isolates with high antibiotic – resistant rates to commonly used antibiotics and increased predominance of major gene types bla TEM is a serious concern to the clinicians and microbiologists. Periodic monitoring of antibiotic susceptibility and associated genes would help guide the rationale use of antibiotics for treating the predominant pathogen E. coli in the hospitals and healthcare facilities of the communities

Feasibility of school-based health education intervention to improve the compliance to mass drug administration for lymphatic Filariasis in Lalitpur district, Nepal: A mixed methods among students, teachers and health program manager.

BACKGROUND:Ensuring reduction in transmission of lymphatic Filariasis (LF) and addressing the compliance of people to mass drug administration (MDA) has led to renewed efforts in the field. School-based health education (SBHE) intervention, considered a cost-effective strategy with potential to reach the wider public through young people, was adopted as a strategy for social mobilization. This study assessed SBHE perceptions, implementation barriers, and factors in the supporting environment as well as its efficiency to successfully change LF MDA-related knowledge and practice. METHODS:This mixed methods study was conducted in four sites of Lalitpur district, Nepal. Classroom-based interactive health education sessions were used as the main intervention strategy in the study. In total, 572 students were assigned to intervention and control groups. Questionnaires were distributed before and after the intervention. Mann-Whitney and McNemar tests were used for analysis. Focus-group discussions with teachers and students and in-depth interviews with the district LF program manager as well as Education Office and school management authorities were conducted. Qualitative thematic analysis approach was adopted. RESULTS:Intervention curriculum played a significant role in increasing children's knowledge and practice (p<0.001). Barriers for school-based interventions were budget constraints, human resource deficiencies, lack of opportunities to conduct practical classes under the curriculum, and lack of collaboration with parents. Supportive factors were training provision, monitoring and evaluation practice, adequate facilities and equipment, positive parental attitudes, presence of interested teachers and students, and prioritization by program implementers. CONCLUSION:Effective program planning practices such as proper fiscal management, human resource management, training mechanisms, and efforts to promote practical classes and coordination with parents are required to develop and institutionalize the intervention. Effective learning and a supportive school environment appear to be important components to support implementation. The SBHE intervention is a feasible and promising intervention for accelerating compliance towards MDA to eliminate LF