Invasive retroperitoneal infection due to basidiobolus ranarum with response to potassium lodide: Case report and review of the literature

We report a case of invasive retroperitoneal zygomycotic infection caused by Basidiobolus ranarum in a healthy 8-year-old boy. The youngster responded dramatically to potassium iodide. The clinical and pathological features are reviewed to highlight the problems encountered in the management of this rare infection

Risk factors for multidrug-resistant tuberculosis in urban Pakistan: A multicenter case-control study

Objective: To evaluate risk factors for multidrug-resistant tuberculosis (MDR-TB) in an urban setting of Pakistan.DESIGN AND Methods: In this multicenter case-control study, patients aged 15years old or older with sputum culture and sensitivity (C/S) diagnosed with pulmonary MDR-TB were defined as cases, whereas patients aged 15years old or older with sputum C/S diagnosed and susceptible to pulmonary TB were regarded as controls. Fifty cases and 75 controls were enrolled from three tertiary-care hospitals in Karachi.Results: Multivariable logistic regression models showed that cases were more likely to have had a TB patient in the house prior to the diagnosis of MDR-TB (adjusted odds ratio [ORadj]=3.1, 95% confidence interval [CI]: 1.2, 8.3) or had a history of prior TB treatment (ORadj=4.2, 95% CI: 1.1, 15.4). Furthermore, cases compared with controls tended to be male (ORadj=3.6, 95% CI: 1.4, 9.7), 15-25years of age (ORadj=3.7, 95% CI: 1.2, 11.3), of Sindhi ethnicity (adjusted OR=9.1, 95% CI: 1.9, 43.4) or with low educational attainment (ORadj OR=5.5, 95% CI: 1.7-17.6, for no formal schooling; ORadj=3.8, 95% CI: 1.1-14.1, 1 for 1-5 school years).CONCLUSIONS: A TB patient in the house or a history of prior TB treatment was strongly associated with MDR-TB in this study. Furthermore, younger age, male gender, Sindhi ethnicity and poor educational attainment entailed a high risk for MDR-TB. Targeted educational intervention for patients and their contacts may minimize the noncompliance with prescribed TB treatment and lessen MDR-TB magnitude in settings like Karachi

Integrating standardized whole genome sequence analysis with a global mycobacterium tuberculosis antibiotic resistance knowledgebase

Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis

A low-cost intervention for cleaner drinking water in Karachi, Pakistan

Objective: To pilot test an inexpensive, home-based water decontamination and storage system in a low-income neighborhood of Karachi.Methods: Fifty households received a 20-L plastic water storage vessel with a high-quality spout and a regular supply of diluted hypochlorite solution. Twenty-five control households were recruited. Water samples were collected at baseline and during unannounced follow-up visits 1, 3, 6, and 10 weeks later.Results: Baseline drinking water samples among intervention households were contaminated with a mean 9397 colony-forming units (cfu)/100 mL of thermotolerant coliforms compared with a mean 10,990 cfu/100 mL from controls. After intervention the mean concentration of thermotolerant coliforms decreased by 99.8% among the intervention households compared with an 8% reduction among controls. Two years after vessel distribution, 34 (68%) of the families were still using the vessel. Thirteen of the households had stopped using their vessel because it had broken after more than 6 months of use, a pattern most consistent with ultraviolet radiation-induced degradation of the plastic.CONCLUSIONS: In a highly contaminated environment, a specifically designed water storage container and in-home water chlorination was acceptable and markedly improved water quality. Where plastic water vessels will be exposed to substantial sunlight, ultraviolet light stabilizers should be incorporated into the plastic

Antimicrobial resistance and COVID-19: Intersections and implications

Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges

Exploring the evidence base for national and regional policy interventions to combat resistance

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains—responsible use, surveillance, and infection prevention and control—and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions

Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase.

Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis

Author Correction: Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Emergence of Carbapenem resistant Gram negative and vancomycin resistant Gram positive organisms in bacteremic isolates of febrile neutropenic patients: A descriptive study

<p>Abstract</p> <p>Background</p> <p>This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant <it>Enterococcus </it>species.</p> <p>Methods</p> <p>A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic patients during the two study periods i.e., 1999–00 and 2001–06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and antibiotic sensitivities were done using standard microbiological procedures.</p> <p>Results</p> <p>Seven twenty six febrile neutropenic patients were admitted during the study period. A total of 5840 blood cultures were received, off these 1048 (18%) were culture positive. Amongst these, 557 (53%) grew Gram positive bacteria, 442 (42%) grew Gram negative bacteria, 43 (4%) fungi and 6 (1%) anaerobes. Sixty (5.7%) out of 1048 positive blood cultures were polymicrobial. In the Gram negative bacteria, <it>Enterobacteriaceae </it>was the predominant group; <it>E. coli </it>was the most frequently isolated organism in both study periods. Amongst non- Enterobacteriaceae group, <it>Pseudomonas aeruginosa </it>was the commonest organism isolated during first study period followed by <it>Acinetobacter </it>spp. However, during the second period <it>Acinetobacter </it>species was the most frequent pathogen.</p> <p><it>Enterobacteriaceae </it>group showed higher statistically significant resistance in the second study period against ceftriaxone, quinolone and piperacillin/tazobactam, whilst no resistance observed against imipenem/meropenem. The susceptibility pattern of <it>Acinetobacter </it>species shifted from sensitive to highly resistant one with significant p values against ceftriaxone, quinolone, piperacillin/tazobactam and imipenem/meropenem. Amongst Gram positive bacteria, MRSA isolation rate remained static, vancomycin resistant <it>Enterococcus </it>species emerged in second study period while no <it>Staphylococcus </it>species resistant to vancomycin was noted.</p> <p>Conclusion</p> <p>This rising trend of highly resistant organisms stresses the increasing importance of continuous surveillance system and stewardship of antibiotics as strategies in the overall management of patients with febrile neutropenia.</p

Demographic and Clinical Features of Dengue Fever in Pakistan from 2003–2007: A Retrospective Cross-Sectional Study

Background: Demographic features of dengue fever have changed tremendously in Pakistan over the past two decades. Small scale studies from all over the country have reported different aspects of individual outbreaks during this time. However, there is scarcity of data looking at the overall trend of dengue virus infection in the country. In this study, we examined annual trends, seasonality, and clinical features of dengue fever in the Pakistani population.Methods: Demographic information and dengue IgM status of all patients tested for dengue IgM antibody at Aga Khan University Hospital from January 2003 to December 2007 were analyzed to look for trends of IgM-positive cases in Pakistan. In addition, clinical and biochemical parameters were abstracted retrospectively from medical records of all patients hospitalized with IgM-proven dengue fever between January 2006 and December 2007. These patients were categorized into dengue fever and dengue hemorrhagic fever according to the WHO severity grading scale.Results: Out of a total of 15040 patients (63.2% male and 36.8% female), 3952 (26.3%) tested positive for dengue IgM antibody. 209 IgM proven dengue patients were hospitalized during the study period. During 2003, IgM positive cases were seen only during the months of July-December. In contrast, such cases were detected throughout the year from the 2004– 2007. The median age of IgM positive patients decreased every year from 32.0 years in 2003 to 24.0 years in 2007 (p,0.001). Among hospitalized patients, nausea was the most common presenting feature found in 124/209 (59.3%) patients. Children presented with a higher median body temperature than adults (p = 0.010). In addition, neutropenia was seen more commonly in children while raised serum ALT levels were seen more commonly in adults (both p = 0.006). While a low total white cell count was more common in patients with dengue fever as compared to Dengue Hemorrhagic Fever (p = 0.020), neutropenia (p = 0.019), monocytosis (p = 0.001) and raised serum ALT level (p = 0.005) were observed more commonly in the latter group.Conclusions: Dengue virus is now endemic in Pakistan, circulating throughout the year with a peak incidence in the post monsoon period. Median age of dengue patients has decreased and younger patients may be more susceptible. Total and differential leukocyte counts may help identify patients at risk of hemorrhage