OBJECTIVES:Yellow fever-associated viscerotropic disease (YEL-AVD) is a rare but serious complication arising from administration of live-attenuated yellow fever vaccine to individuals with risk factors such as thymectomy. At present there is no evidence-based treatment, and case fatality rates are high. Sofosbuvir, an NS5B nucleotide inhibitor, has activity against yellow fever virus in vitro and in vivo. PATIENT AND METHODS:Here we describe clinical and virological response to use of off-licence sofosbuvir as post-exposure prophylaxis for a patient inadvertently given yellow fever vaccine despite previous thymectomy. RESULTS:A 14-day course of oral sofosbuvir was administered in an outpatient setting with regular clinical and biochemical monitoring. The patient remained well without developing clinical features of YEL-AVD and did not experience adverse effects from the treatment. CONCLUSIONS:This supports the use of sofosbuvir as post-exposure prophylaxis in patients at high risk of developing YEL-AVD. Ongoing trials of efficacy of sofosbuvir in yellow fever infection may result in stronger support for this approach in the future.

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.

Background Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. Method This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7–1.0 mg/kg) and oral fluconazole (800 mg orally/day). Results Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. Conclusion Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

Abstract Background Lower respiratory infections constitute a major disease burden worldwide. Treatment is usually empiric and targeted towards typical bacterial pathogens. Understanding the prevalence of pathogens not covered by empirical treatment is important to improve diagnostic and treatment algorithms. Methods A prospective observational study in peri-urban communities of Yangon, Myanmar was conducted between July 2018 and April 2019. Sputum specimens of 299 adults presenting with fever and productive cough were tested for Mycobacterium tuberculosis (microscopy and GeneXpert MTB/RIF [Mycobacterium tuberculosis/resistance to rifampicin]) and Burkholderia pseudomallei (Active Melioidosis Detect Lateral Flow Assay and culture). Nasopharyngeal swabs underwent respiratory virus (influenza A, B, respiratory syncytial virus) polymerase chain reaction testing. Results Among 299 patients, 32% (95% confidence interval [CI] 26 to 37) were diagnosed with tuberculosis (TB), including 9 rifampicin-resistant cases. TB patients presented with a longer duration of fever (median 14 d) and productive cough (median 30 d) than non-TB patients (median fever duration 6 d, cough 7 d). One case of melioidosis pneumonia was detected by rapid test and confirmed by culture. Respiratory viruses were detected in 16% (95% CI 12 to 21) of patients. Conclusions TB was very common in this population, suggesting that microscopy and GeneXpert MTB/RIF on all sputum samples should be routinely included in diagnostic algorithms for fever and cough. Melioidosis was uncommon in this population.

The 2019 novel coronavirus disease (COVID-19) pandemic highlights the experience of communities in the global South that have grappled with vulnerability and scarcity for decades. In the global North, many frontline workers are now being similarly forced to provide and ration care in unprecedented ways, with minimal guidance. We outline six reflections gained as Western practitioners working in resource-denied settings which inform our current experience with COVID-19. The reflections include the following: managing trauma, remaining flexible in dynamic situations, and embracing discomfort to think bigger about context-specific solutions to collectively build back our systems. Through this contextualized reflection on resilience, we hope to motivate strength and solidarity for providers, patients, and health systems, while proposing critical questions for our response moving forward.

British Journal of Hospital MedicineVol. 81, No. 11 Case ReportAn immunocompromised Albanian farmer with a Mediterranean menaceClare E Warrell, Thomas Pichl, Ian Cropley, Tabitha Mahungu, Robert F MillerClare E WarrellCorrespondence to: Clare E Warrell; E-mail Address: [email protected]Infectious Diseases Department, Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this author, Thomas PichlInfectious Diseases Department, Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this author, Ian CropleyInfectious Diseases Department, Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this author, Tabitha MahunguInfectious Diseases Department, Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this author, Robert F MillerInfectious Diseases Department, Royal Free London NHS Foundation Trust, London, UKInstitute for Global Health, University College London, London, UKSearch for more papers by this authorClare E Warrell; Thomas Pichl; Ian Cropley; Tabitha Mahungu; Robert F MillerPublished Online:1 Dec 2020https://doi.org/10.12968/hmed.2020.0019AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View articleReferencesAronson N, Herwaldt BL, Libman Met al.. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016;63(12):e202–e264. https://doi.org/10.1093/cid/ciw670 Crossref, Medline, Google ScholarBadaró R, Gonçalves LO, Gois LLet al.. Leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients: a literature review. J Int Assoc Provid AIDS Care. 2015;14(5):402–407. https://doi.org/10.1177/2325957414555225 Crossref, Medline, Google ScholarLawn SD, Wilkinson RJ. Immune reconstitution disease associated with parasitic infection following antiretroviral treatment. Parasite Immunol. 2006;28(11):625–633. https://doi.org/10.1111/j.1365-3024.2006.00900.x Medline, Google ScholarLindoso JAL, Moreira CH, Cunha MA, Queiroz IT. Visceral leishmaniasis and HIV coinfection: current perspectives. HIV AIDS. 2018;10:193–201. https://doi.org/10.2147/HIV.S143929 Google Scholarvan Griensven J, Mohammed R, Ritmeijer K, Burza S, Diro E. Tuberculosis in visceral leishmaniasis-human immunodeficiency virus coinfection: an evidence gap in improving patient outcomes? Open Forum Infect Dis. 2018;5(4):ofy059. https://doi.org/10.1093/ofid/ofy05910.1093/ofid/ofy059 Crossref, Medline, Google ScholarWalker NF, Scriven J, Meintjes G, Wilkinson RJ. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV/AIDS (Auckl). 2015;7:49–64. https://doi.org/10.2147/HIV.S42328 Medline, Google Scholar FiguresReferencesRelatedDetails 2 November 2020Volume 81Issue 11ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 1 December 2020 Published in print 2 November 2020 Information© MA Healthcare LimitedAcknowledgementsThe authors would like to thank the patient and his family for consent to use his case for educational purposes, Dr Rob Davidson and Professor Diana Lockwood for their advice in management of this case, and Dr Ula Mahedeva for reviewing the bone marrow trephines.PDF download

INTRODUCTION:Determining the cause of eosinophilia in patients returning from the tropics continues to present a diagnostic challenge. The history, symptoms and degree of eosinophilia are often poor predictors of eventual diagnosis, but helminths are an important cause. The current British Infection Association recommendations use travel history to guide investigation of eosinophilia. However the global burden of helminth disease and travel patterns have changed over the last 3 decades and guidelines based on previous epidemiology need to be reviewed in the light of current data. METHODS:Consecutive patients presenting with, or referred for, investigation of eosinophilia were identified prospectively. Case notes, laboratory results and electronic records were reviewed for demographic and clinical data. Patients with an eosinophil count ≥0.50 × 109/L were included, and grouped based on lifetime history of travel to: West Africa, elsewhere in Africa, and the rest of the world. Results were compared to published data from 1997 to 2002 collected at the same centre. RESULTS:Of 410 patients who met the inclusion criteria, 407 had a documented travel history. Average yearly referrals for eosinophilia fell from 58 per year between 1997 and 2002, to 33 per year (2002-2015). The proportion of eosinophilia cases diagnosed with a parasitic cause fell from 64% to 50%, and yields for all parasitological investigations fell, the largest reduction in stool microscopy (20% yield to 9%) and day bloods for microfilariae (14% yield to 3%). Strongyloides stercoralis was the commonest diagnosis overall in our cohort, accounting for 50% of the total parasites diagnosed, and was present in 38% of patients from West Africa, 19% from rest of Africa, and 34% from rest of world; a relative increase compared to previous data. Schistosomiasis is slightly less common in those who had travelled to West Africa than the rest of Africa, and overall point prevalence has fallen from 33% (1997-2002) to 17% (2002-2015). Travellers were significantly less likely than patients who had immigrated to the UK to be diagnosed with any parasite (OR 0.54 95% CI 0.378-0.778 p = 0.0009). DISCUSSION:A parasitic cause will still be found in half of people returning from the tropics with an eosinophilia, but we observed a fall in the overall prevalence of parasitic diagnoses when compared with the earlier data. This may, in part, be explained by the impact of control programmes on the prevalence of parasites globally, especially filarial disease. S. stercoralis now represents the majority of parasites diagnosed in our cohort from all continents. We identified significantly higher rates of strongyloidiasis in immigrants than returning travellers. Despite the falling yields of stool microscopy and filarial serology the current guidelines based on travel history remain relevant with adequate yield.

Primary cerebral phaeohyphomycosis due to Rhinocladiella mackenziei is an extremely rare infection carrying more than 80% mortality, with most cases reported from the Middle East region. This darkly pigmented black yeast is highly neurotropic, aggressive and refractory to most antifungal agents. Here we present an immunocompetent elderly male, presenting with multiple brain abscesses, with R. mackenziei confirmed by nuclear ribosomal repeat region sequencing, who was successfully treated by surgical debridement and intravenous voriconazole. To our knowledge this is the first case reported from the United Kingdom. We also present a review of all such cases so far reported in the English literature world-wide, which we believe is a step further to understanding the pathogenesis and establishing effective treatment of this rare, yet often fatal disease.