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Eosinophilia is a common finding in returning travellers, migrants and other travelling groups. In this setting it often indicates an underlying helminth infection. Infections associated with eosinophilia are frequently either asymptomatic or associated with non-specific symptoms but some can cause severe disease. Here the British Infection Association guidelines group has comprehensively reviewed and updated the UK recommendations for the investigation and management of eosinophilia in returning travellers, migrants and other relevant groups, first published in 2010. 1 Literature reviews have been undertaken to update the evidence on the prevalence and causes of eosinophilia in these groups and on the treatment of relevant pathogens and clinical conditions. Diagnostic tests available to UK-based clinicians are summarised. Changes made to the updated guidelines include in sections on the investigation and empirical treatment of asymptomatic eosinophilia and on the treatment of trichuriasis, lymphatic filariasis, onchocerciasis, hookworm, fascioliasis, taeniasis. Pathogens which are rarely encountered in UK practice have been removed from the guidelines and others added, including an expanded section on fungal infection. A section on off-license and rarely used drugs has been included., (Copyright © 2024. Published by Elsevier Ltd.)

We describe a case of autochthonous human Babesia divergens infection in an immunocompetent woman in England. The patient had fever, hemolysis, multiorgan failure, and 18% parasitemia. We confirmed B. divergens by 18S rDNA PCR and sequencing. Clinicians should consider babesiosis as a differential diagnosis in patients with unexplained hemolysis.

Background: Recent cases of clinical failure in malaria patients in the United Kingdom (UK) treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide., Methods: Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor., Results: A traveler, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival, 17.3% [95% confidence interval {CI}, 13.6%-21.1%]; P < .0001) and lumefantrine (effective concentration preventing 50% of growth = 259.4 nM [95% CI, 130.6-388.2 nM]; P = .001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V nonpropeller variant. In vitro susceptibility testing of 6 other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in 1 additional line, also from a 2022 treatment failure case. These parasites did not harbor a pfk13 propeller domain variant but rather the novel nonpropeller variant T349I. Variant alleles of pfubp1, pfap2mu, and pfcoronin were also identified among the 7 parasite lines., Conclusions: We confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda., Competing Interests: Potential conflicts of interest. B. C. Y. reports a clinical lecturer starter grant paid via institution from Academy of Medical Sciences and funding to institution from the Oxford University National Institute for Health and Care Research Biomedical Research Centre grant. P. L. C. reports grants or contracts from the World Health Organization for the Molecular External Quality Assessment Scheme. J. M. reports grant to institution 203919/Z/16/Z from Wellcome Trust Clinical PhD and grant to institution from UCL Global Challenges, and participation as chair of a data and safety monitoring board for Triage Test for All Oral DR-TB Regimen (TRiAD Study). L. E. N. reports royalties or licenses paid to author from Peter’s Atlas of Tropical Medicine and Parasitology (Elsevier, author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Healthcare-associated invasive group A Streptococcus (iGAS) outbreaks are common worldwide, but only England has reported outbreaks associated with home healthcare (HHC). We describe 10 outbreaks during 2018-2019 in England. A total of 96 iGAS cases (range 2-39 per outbreak) and 28 deaths (case-fatality rate 29%) occurred. Outbreak duration ranged from 3-517 days; median time between sequential cases was 20.5 days (range 1-225 days). Outbreak identification was difficult, but emm typing and whole-genome sequencing improved detection. Network analyses indicated multiple potential transmission routes. Screening of 366 HHC workers from 9 outbreaks identified group A Streptococcus carriage in just 1 worker. Outbreak control required multiple interventions, including improved infection control, equipment decontamination, and antimicrobial prophylaxis for staff. Transmission routes and effective interventions are not yet clear, and iGAS outbreaks likely are underrecognized. To improve patient safety and reduce deaths, public health agencies should be aware of HHC-associated iGAS.

Enteric fever (EF) is an infection caused by the bacteria called Salmonella Typhi or Paratyphi. Infection is acquired through swallowing contaminated food or water. Most EF in England occurs in people returning from South Asia and other places where EF is common; catching EF in England is rare. The main symptom is fever, but stomach pain, diarrhoea, muscle aches, rash and other symptoms may occur. EF is diagnosed by culturing the bacteria from blood and/or stool in a microbiology laboratory. EF usually responds well to antibiotic treatment. Depending on how unwell the individual is, antibiotics may be administered by mouth or by injection. Over the past several years, there has been an overall increase in resistance to antibiotics used to treat enteric fever, in all endemic areas. Additionally, since 2016, there has been an ongoing outbreak of drug-resistant EF in Pakistan. This infection is called extensively drug-resistant, or XDR, EF and only responds to a limited number of antibiotics. Occasionally individuals develop complications of EF including confusion, bleeding, a hole in the gut or an infection of the bones or elsewhere. Some people may continue to carry the bacteria in their stool for a longtime following treatment for the initial illness. These people may need treatment with a longer course of antibiotics to eradicate infection. Travellers can reduce their risk of acquiring EF by following safe food and water practices and by receiving the vaccine at least a few weeks before travel. These guidelines aim to help doctors do the correct tests and treat patients for enteric fever in England but may also be useful to doctors and public health professionals in other similar countries., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Infections caused by carbapenem resistant K. pneumoniae are increasing and associated with high mortality rates. There are increasing reports of hypermucoviscous/ hypervirulent K. pneumoniae isolated from various sources. However, there is limited data on the prevalence of hypermucoviscous strains among carbapenem-resistant K. pneumoniae from invasive infections in India and its association with mortality. rmpA, rmpA2 and magA genes are associated with these hypervirulent strains. In this study, we investigate the prevalence of hypermucoviscous strains amongst carbapenem resistant K. pneumoniae isolated from blood culture. Association of mortality rate with meropenem minimum inhibitory concentration and hypermucoviscous strains are determined., Methods: 86 non-repetitive carbapenem resistant K. pneumoniae isolated from bacteremia underwent E-test for meropenem minimum inhibitory concentration (MIC) determination and PCR for detection of carbapenamase genes. String test, PCR for rmpA, rmpA2 and magA were performed for characterisation of hypervirulent strains. Results: 31.3% of the 86 isolates displayed hypermucoviscous phenotype as indicated by a positive string test. Among the two genotypic markers, 7% were positive for rmpA2 and all were negative for rmpA and magA. 74.1% and 67.9% mortality were seen among string test positives and isolates meropenem MIC of ≥16µg/ml respectively (p 0.036 and 0.008 respectively). Isolates with both string positivity and meropenem MIC of ≥16µg/ml had a very high mortality rate of 84.2%., Conclusion: String test, aids prediction of disease severity, and is independently associated with increased mortality in invasive carbapenem resistant K.pneumoniae health care-acquired infections. High meropenem MIC is a significant risk factor for mortality. Combination of string positive carbapenem resistant hypermucoviscous K. pneumoniae resulted in mortality rate of 84.2%. It is important to monitor prevalence of carbapenem resistant hypermucoviscous/hypervirulent K. pneumoniae among invasive isolates especially in a setting with high resistance rates as combination of increased virulence and decreased susceptibility to antimicrobials results in worse outcomes., (© Journal of the Association of Physicians of India 2011.)

Background: Giardia intestinalis is microaerophilic diarrhoea-causing protozoan common in countries with suboptimal sanitation. Standard treatment is with nitroimidazoles, but a growing number of refractory cases is being reported. Treatment failure has become increasingly prevalent in travellers who contract giardiasis in Asia. Clinicians are increasingly falling back on second-line and less well-known drugs to treat giardiasis., Aims: To review nitroimidazole-refractory G. intestinalis infection, examine the current efficacy of standard therapeutic agents, consider potential resistance mechanisms which could cause treatment failure and describe the practical aspects of managing this emerging clinical problem., Sources: A PubMed search was conducted using combinations of the following terms: refractory, Giardia, giardiasis, resistance and treatment. Articles on the pharmacotherapy, drug resistance mechanisms and use of alternative agents in nitroimidazole-refractory giardiasis were reviewed., Content: We review the standard drugs for giardiasis, including their efficacy in initial treatment, mode of action and documented in vitro and in vivo drug resistance. We assess the efficacy of alternative drugs in nitroimidazole-refractory disease. Existing data suggest a potential advantage of combination treatment., Implications: An optimal treatment strategy for refractory giardiasis has still to be determined, so there is no standard treatment regimen for nitroimidazole-refractory giardiasis. Further work on drug resistance mechanisms and the use of drug combinations in this condition is a priority., (Copyright © 2017. Published by Elsevier Ltd.)

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 bla OXA-48 like , one co-expressed bla NDM-1 and bla OXA-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.

The dissemination of methicillin-resistant (MR) Staphylococcus aureus (SA) in community and health-care settings is of great concern and associated with high mortality and morbidity. Rapid detection of MRSA with short turnaround time can minimize the time to initiate appropriate therapy and further promote infection control. Early detection of MRSA directly from clinical samples is complicated by the frequent association of MRSA with methicillin-susceptible SA (MSSA) and coagulase-negative Staphylococcus (CoNS) species. Infection associated with true MRSA or MSSA is differentiated from CoNS, requires target specific primers for the presence of SA and mec A or nuc or fem A gene for confirmation of MR. Recently, livestock-associated MRSA carrying mec C variant complicates the epidemiology of MRSA further. Several commercial rapid molecular kits are available with a different combination of these targets for the detection of MRSA or MSSA. The claimed sensitivity and specificity of the currently available commercial kits is varying, because of the different target combination used for detection of SA and MR., Competing Interests: There are no conflicts of interest.

Hypervirulent Klebsiella pneumoniae strains have been increasingly reported worldwide, and there is emergence of carbapenem resistance among them. Here, we report the genome sequences of three carbapenem-resistant hypervirulent K. pneumoniae isolates isolated from bacteremic patients at a tertiary-care center in South India., (Copyright © 2016 Shankar et al.)

Enteric fever is a major cause of morbidity and mortality in tropical areas worldwide. The Indian subcontinent bears the brunt of the disease, both in terms of absolute case numbers and drug-resistant strains. Recent phylogenetic studies suggest that the multidrug-resistant clade H58 originated in India and subsequently expanded through Asia and Africa. In Africa, it caused unrecognised outbreaks in areas previously considered free of the disease. In this study, we discuss the current status of enteric fever in India, the factors preventing its control and its future directions in this rapidly developing nation., (© 2016 John Wiley & Sons Ltd.)

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a high mortality rate and are an increasing problem worldwide. In this mini-review, we consider the growing number of observational studies in favour of combination therapy but highlight the absence of randomised control trials. We discuss the importance of data on minimum inhibitory concentrations (MICs), both for surveillance and for individual patient management. We examine the issues surrounding the use of carbapenems, polymyxins and tigecycline in the treatment of CRE. When and how should we be using carbapenems? Which polymyxin is best? Is tigecycline much maligned? Further studies are urgently needed to validate drug combinations, doses and ratios to maximise efficacy whilst reducing drug exposure and adverse effects.

Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Cystic echinococcosis (CE) is a significant public health problem worldwide. However, there remains a dearth of evidence guiding treatment in various stages of CE. The 2010 World Health Organization (WHO) Informal Working Group on Echinococcosis (WHO IWGE) guidance is thus based on expert consensus rather than a good evidence base. This study aims to describe the way clinicians worldwide manage CE and to establish whether clinicians follow WHO IWGE guidance., Methods: Using the online surveying tool SurveyMonkey, a questionnaire was produced detailing 5 clinical cases. Clinicians treating CE were identified and asked how to manage each case through tick-box and short-answer questions., Results: The results showed great variation in practice worldwide. There are practices in common use that are known to be ineffectual, including puncture, aspiration, injection, reaspiration procedures on WHO type 2 cysts, or outdated, including interrupted, rather than continuous, courses of albendazole. A number of unsafe practices were identified such as using scolicidal agents in cysts communicating with the biliary tree and short-course medical therapy for disseminated disease. Most clinicians do not follow the WHO IWGE guidance, but the reasons for this are unclear., Conclusions: Management of CE varies greatly worldwide. There are key areas of CE for which there is no evidence on which to base guidelines, and randomized controlled trials are needed together with a well-designed international registry to collect data. Further work is required to establish why clinicians do not follow the IWGE guidance, together with better dissemination of future guidance., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)