Transmission of SARS-CoV-2 in standardised first few X cases and household transmission investigations: A systematic review and meta-analysis.

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2 = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

A second external quality assessment of isolation and identification of influenza viruses in cell culture in the Asia Pacific region highlights improved performance by participating laboratories.

Influenza viruses must be amplified in cell culture for detailed antigenic analysis and for phenotypic assays assessing susceptibility to antiviral drugs or for other assays. Following on from the first external quality assessment (EQA) for isolation and identification of influenza viruses using cell culture techniques in 2016, a follow up EQA was performed in 2019 for National Influenza Centres (NICs) in the World Health Organization (WHO) South East Asia and Western Pacific Regions. Nineteen WHO NICs performed influenza virus isolation and identification techniques on an EQA panel comprising 16 samples, containing influenza A or B viruses and negative control samples. One sample was used exclusively to assess capacity to measure a hemagglutination titer and the other 15 samples were used for virus isolation and subsequent identification. Virus isolation from EQA samples was generally detected by assessment of cytopathic effect and/or hemagglutination assay while virus identification was determined by real time RT-PCR, hemagglutination inhibition and/or immunofluorescence assays. For virus isolation from EQA samples, 6/19 participating laboratories obtained 15/15 correct results in the first EQA (2016) compared to 11/19 in the follow up (2019). For virus identification in isolates derived from EQA samples, 6/19 laboratories obtained 15/15 correct results in 2016 compared to 13/19 in 2019. Overall, NIC laboratories in the Asia Pacific Region showed a significant improvement between 2016 and 2019 in terms of the correct results reported for isolation from EQA samples and identification of virus in isolates derived from EQA samples (p=0.01 and p=0.02, respectively).

Pandemic influenza preparedness in the WHO South-East Asia Region: a model for planning regional preparedness for other priority high-threat pathogens.

Pandemic influenza preparedness has contributed significantly to building, strengthening and maintaining countries' core capacities to prepare for health emergencies. The Pandemic influenza preparedness framework for the sharing of influenza viruses and access to vaccines and other benefits (the PIP framework) was adopted by the World Health Assembly in 2011. The experiences and lessons learnt from the implementation of the PIP framework have provided insights that can be used to strengthen preparedness for epidemics of other priority high-threat pathogens in the World Health Organization (WHO) South-East Asia Region in line with obligations under the International Health Regulations, 2005 (IHR). Implementation has established policies, strategies, action plans, strengthened systems and operational readiness to promptly diagnose influenza virus strains with pandemic potential and ensure timely event notifications and management in compliance with the IHR. WHO collaborating centres and the annual bi-regional meeting of national influenza centres and influenza surveillance have strengthened the influenza laboratory diagnostic knowledge network in the region. After action reviews following influenza outbreaks have documented best practices, strengths, constraints and areas for improvement in pandemic preparedness. The pandemic in 2009 and recent seasonal influenza outbreaks have offered real-life scenarios for testing national pandemic influenza preparedness plans and deploying vaccines. The successful implementation of the PIP framework, along with strengthening of health systems and operational procedures and continued technical collaboration with global centres of excellence, should be tapped into to strengthen preparedness to respond to epidemics of other high-threat pathogens based on the influenza model. The political commitment reflected in the Delhi Declaration on Emergency Preparedness, signed by all ministers of health in September 2019 and supported by the Five-year regional strategic plan to strengthen public health preparedness and response - 2019-2023, should be a catalyst for guidance and support in developing a broad, long-term strategic plan for preparedness and response to high-threat pathogens in the region.

Molecular Mechanisms of Colistin Resistance in Klebsiella pneumoniae Causing Bacteremia from India-A First Report.

Colistin has long been a reserve drug used for the treatment of carbapenem resistant Klebsiella pneumoniae. Carbapenem resistance in K. pneumoniae has been increasing and is as high as 44% in India. Although a reserve agent, with rise in rates of resistance to carbapenems, the usage of colistin has increased over the years leading to slow emergence of resistance. Colistin resistance is mainly mediated by the alteration in the LPS of bacterial outer membrane with the addition of L-Ara4-N and PEtN molecules. These alterations are mediated by mutations in several genes involved in lipidA modifications and most commonly mutations in mgrB gene has been reported. Recently there is emergence of plasmid mediated resistance due to mcr-1 and mcr-2 genes which poses a threat for the rapid global spread. This study aims at characterizing eight colistin resistant K. pneumoniae from bacteremia by whole genome sequencing. Eight K. pneumoniae were isolated from blood culture during 2013 and 2014 at the Department of Clinical Microbiology, Christian Medical College, India. Antimicrobial susceptibility testing was performed and minimum inhibitory concentration (MIC) was determined for colistin and polymyxin B by broth-micro dilution method. Whole genome sequencing was performed using Ion Torrent and the genome of all eight isolates was analyzed. The eight isolates were resistant to all the antimicrobials expect tigecycline. MIC of colistin and polymyxin B were ranged from 4 to 1024 µg/ml and 0.5 to 2048 µg/ml respectively. Multiple mutations were observed in the chromosomal genes involved in lipid A modifications. mcr-1 and mcr-2 gene was absent in all the isolates. The most significant were mutations in mgrB gene. Among the eight isolates, four, three and one were belonged to sequence types ST 231, ST14 and ST147 respectively. Seven isolates had blaOXA-48 like, one co-expressed blaNDM-1 and blaOXA-48 like genes leading to carbapenem resistance. Overall, multiple numbers of alterations have been observed. This includes silent mutations, point mutations, insertions and/or deletions. Mutations in mgrB gene is responsible for resistance to colistin in this study. Due to emergence of resistance to reserve drugs, there is a need for combination therapies for carbapenem resistant K. pneumoniae and colistin must be judiciously used.