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The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022. Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection. 220 patients had rickettsioses, and the commonest import was acute spotted fever group infection (61%, 125/205), 54% (62/114) from South Africa. In acute typhus group cases, 60% (40/67) were from Southeast Asia. One patient with Rickettsia typhi bacteremia died. Scrub typhus group infections (5%, 10/205) were exclusively from Asia and the Western Pacific regions. Overall, 43% of confirmed cases (39/91) had not received doxycycline prior to results. Rickettsial infections are important and under-recognized causes of imported fever in the UK. Thorough history, examination, and timely treatment with doxycycline should be considered if there is suspicion of Rickettsia infection before testing. • Rickettsial infections are a major cause of non-malarial fever. • The UKHSA Rare and Imported Pathogens Laboratory provides rickettsial diagnostics; acute and convalescent serology and PCR. • Timely treatment with doxycycline is encouraged in suspected cases of rickettsial infection. [ABSTRACT FROM AUTHOR]

The first reported snakebite by an African snake-eater, Polemon spp. (Atractaspididae, Aparallactinae); Local envenoming by Reinhardt's snake-eater, Polemon acanthias (Reinhardt, 1860). Toxicon XX, xxx. A 51-yr-old male herpetologist was bitten on the left index finger by a captive male Polemon acanthias while manually removing fragments of incompletely shed skin from the specimen. The snake sustained its bite for approximately 2 mins, advancing its jaws several times. The victim rapidly developed moderate pain, erythema, progressive edema that ultimately extended to the left wrist; a blister later developed in the wound site, as well as joint stiffness in the bitten and adjacent two fingers that limited flexion and extension. These effects regressed during the week following the bite, but recurred thereafter and were similar to the effects that developed immediately post-envenoming. There were no systemic signs or symptoms. The victim sought medical advice and was treated with broad-spectrum antibiotics, antihistamines and wound care; no laboratory investigations were conducted. He improved during the subsequent month with complete resolution in 5 and one-half weeks. This is the first documented bite by a Polemon spp. and the victim's clinical course suggests the development of local effects from venom components. The phylogenetic relationship of Polemon spp. with the burrowing asps (Atractaspis spp.) and the similarity of some of the features of this local envenoming by P. acanthias with mild/moderate envenoming by some Atractaspis spp., suggests that none of these snakes should be handled; they should be considered capable of inflicting potentially serious envenoming. • A local envenoming by Reinhardt's snake-eater, Polemon acanthias (Atractaspididae, Aparallactinae) is reported. • The report is the first formally documented bite by any Polemon spp. • The victim developed moderate pain, progressive edema and blistering; there were no systemic symptoms/signs. • The local effects recurred several days after almost complete resolution. • Treatment was mainly supportive and full resolution occurred after 5.5 weeks. [ABSTRACT FROM AUTHOR]

Highlights • This 2 visit 4-site ID PEP regimen is derived from the original 8-site ID PEP regimen. • A whole vial is used in 4-sites ID on day 0, and half a vial at 2-sites ID on day 7. • This regimen would be economical and suitable for rural Asian and African clinics. • A dose on day 28 is advisable after any 1 week regimen for immunosuppressed patients. • That becomes the 4-site ID one month regimen which is now recommended by WHO. Abstract Rabies is fatal in all unvaccinated patients bitten by dogs, and so post-exposure vaccine regimens must be robust enough to ensure their survival under all conditions. Treatment tends to be excessive for most people, but there is justified anxiety about reducing vaccine dosage and shortening regimens. Recently, World Health Organisation (WHO) recommended one week primary post-exposure intradermal regimens requiring 3 clinic visits, but these are unlikely to prove economical where rabies vaccination is most needed, in deprived rural areas of Africa and Asia. A highly immunogenic regimen involving two doses of intradermal vaccine given one week apart has advantages over other regimens. Anyone exposed to a possibly rabid animal would be given intradermal (ID) injections at 4 sites using a whole vial of vaccine. Those who had not been previously vaccinated would be given 2-site ID injections using half a vial one week later. Those who might be immunosuppressed could be given an optional single ID dose on day 28. The rationale for this regimen is discussed in the context of the recently revised WHO recommendations for rabies prophylaxis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: In West Africa, response to specific, geographically appropriate, antivenom is often dramatic following carpet viper (Echis ocellatus) envenoming with rapid restoration of blood coagulability and resolution of spontaneous haemorrhage. Envenoming from Australasian snakes causing similar coagulopathies may respond less dramatically and the effectiveness of antivenom is being questioned. Here we have reviewed and re-analysed all published preclinical and clinical studies on envenoming and antivenom therapy conducted in West Africa to determine the effectiveness of antivenom. 22 studies provided relevant information: 12 observational studies, 4 RCTs and 6 preclinical studies. Four comparative studies confirmed statistically significant protection against mortality ranging from 57 to 87% using specific antivenoms compared to non-specific or no antivenoms. Meta-analysis estimated combined Odds Ratio (95% CI) of 0.25 (0.14–0.45) of dying among those treated with specific antivenom or 75% (95% CI: 55–86%) protection against death. Mortality more than doubled during times when stocks of reliable antivenoms ran out, with Relative Risk (95% CI)] of 2.33 (1.26–4.06). Serum kinetics of venom antigen/antivenom levels also confirmed that decline of venom antigen levels coincided with resolution of coagulopathy while decline of antivenom levels was associated with venom antigen reappearance and recurrence of coagulopathy. Preclinical and antivenomics analysis confirmed efficacy of regionally appropriate antivenoms against E. ocellatus and related species' venoms in Sub-Saharan Africa but not against Asian Echis carinatus venom. Antivenoms raised against E. carinatus were ineffective in human studies. In West Africa, specific antivenom is effective in managing carpet viper envenoming. A centralized hub-and-spoke strategy is suggested for broadening antivenom access to endemic rural areas together with instituting quality assurance, standardization and manpower training. Benefits, risks, cost-effectiveness and feasibility of the approach should be formally assessed. [Copyright &y& Elsevier]

Abstract: Research is discussed in the areas of venomous snake taxonomy, epidemiology, species diagnosis, defining the clinical phenotype of human envenoming, pathophysiological mechanisms of envenoming, clinical testing of antivenoms and prevention of snake-bite through community education. This work was carried out over the past 40 years in many countries in four tropical continents. The help and friendship of a large number of collaborators is gratefully acknowledged. [Copyright &y& Elsevier]

Summary: Travellers are probably the largest group in the general population to receive rabies pre-exposure prophylaxis. The dangerous consequences of the unavailability of rabies immune globulin in many countries could be ameliorated if pre-exposure rabies vaccination were practised more widely, especially in children, living in dog rabies enzootic countries. The WHO has recommended several different regimens for post-exposure prophylaxis, while individual countries decide on protocols for local use. Intramuscular regimens are expensive and waste vaccine. Although failure to receive vaccine is usually the due to the cost, the economical potential of intradermal vaccination has still not been realised 19 years after its introduction. The currently recommended 2-site intradermal post-exposure regimen is not economical for use in rural areas where 80% of Indian rabies deaths occur. Most countries using it demand higher potency vaccine, indicating that they do not have complete confidence in the method. This intradermal regimen has only been used where immunoglobulin is likely to be available for severely bitten patients. Increased intradermal doses are sometimes used for selected patients. Provision of economical rabies prophylaxis can be improved. Decisions to change recommendations should take account of the immunological, financial, practical and logistical aspects of dog bite treatment in remote areas. [Copyright &y& Elsevier]

Summary: International travel is increasing. Most physicians and general practitioners will encounter returned travellers with fever and the majority of travel-related infection is associated with travel to the tropics. In those returning from the tropics malaria must always be excluded, and HIV considered, from all settings. Common causes of non-malarial fever include from Africa rickettsial diseases, amoebic liver abscess and Katayama syndrome; from South and South East Asia, enteric fever and arboviral infection; from the Middle East, brucellosis and from the Horn of Africa visceral leishmaniasis. Other rare but important diseases from particular geographical areas include leptospirosis, trypanosomiasis and viral haemorrhagic fever. North and South America, Europe and Australia also have infections which are geographically concentrated. Empirical treatment may have to be started based on epidemiological probability of infection whilst waiting for results to return. The evidence base for much of the management of tropical infections is limited. These recommendations provide a pragmatic approach to the initial diagnosis and management of fever in returned travellers, based on evidence where it is available and on consensus of expert opinion where it is not. With early diagnosis and treatment the majority of patients with a potentially fatal infection related to travel will make a rapid and full recovery. [Copyright &y& Elsevier]

Summary: Malaria is the tropical disease most commonly imported into the UK, with 1500–2000 cases reported each year, and 10–20 deaths. Approximately three-quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other two species of Plasmodium: Plasmodium ovale or Plasmodium malariae. Mixed infections with more than 1 species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until 3 blood specimens have been examined by an experienced microscopist. There are no typical clinical features of malaria, even fever is not invariably present. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites; P. falciparum malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens or enzymes, although RDTs for other Plasmodium species are not as reliable. The treatment of choice for non-falciparum malaria is a 3-day course of oral chloroquine, to which only a limited proportion of P. vivax strains have gained resistance. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine. This must be avoided or given with caution under expert supervision in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. Uncomplicated P. falciparum malaria can be treated orally with quinine, atovaquone plus proguanil (Malarone®) or co-artemether (Riamet®); quinine is highly effective but poorly tolerated in prolonged dosage and is always supplemented by additional treatment, usually with oral doxycycline. ALL patients treated for P. falciparum malaria should be admitted to hospital for at least 24h, since patients can deteriorate suddenly, especially early in the course of treatment. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized), should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. In the UK, the treatment of choice for severe or complicated malaria is currently an infusion of intravenous quinine. This may exacerbate hypoglycaemia that can occur in malaria; patients treated with intravenous quinine therefore require careful monitoring. Intravenous artesunate reduces high parasite loads more rapidly than quinine and is more effective in treating severe malaria in selected situations. It can also be used in patients with contra-indications to quinine. Intravenous artesunate is unlicensed in the EU. Assistance in obtaining artesunate may be sought from specialist tropical medicine centres, on consultation, for named patients. Patients with severe or complicated malaria should be managed in a high dependency or intensive care environment. They may require haemodynamic support and management of acute respiratory distress syndrome, disseminated intravascular coagulation, renal impairment/failure, seizures, and severe intercurrent infections including gram-negative bacteraemia/septicaemia. Falciparum malaria in pregnancy is more likely to be severe and complicated: the placenta contains high levels of parasites. Stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. The treatment of choice for falciparum malaria in pregnancy is quinine; doxycycline is contraindicated in pregnancy but clindamycin can be substituted for it, and is equally effective. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy; after treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery when hypnozoite eradication can be considered. Children are over-represented in the incidence of malaria in the UK, probably because completely susceptible UK-born children accompany their overseas-born parents on visits to family and friends in endemic areas. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints; the diagnosis must always be sought in a feverish or very sick child who has visited malaria-endemic areas. Children can be treated with most of the antimalarial regimens which are effective in adults, with appropriate dosage adjustment. Doxycycline plus quinine should not be given to children under 12 years as doxycycline is contraindicated in this age group, but clindamycin can be substituted for doxycycline, and pyrimethamine–sulfadoxine (Fansidar®) may also be an effective substitute. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas. [Copyright &y& Elsevier]

A workshop to discuss progress in the standardization and control of antivenoms, organized by the Quality Assurance and Safety of Biologicals Unit of WHO, was held at the National Institute for Biological Standards and Control, Potters Bar, England, 7–9 February 2001. This was the first meeting convened by the WHO on this subject since 1979 and it brought together experts from academic institutions, antivenom manufacturers and national regulatory authorities from 21 countries. The meeting reviewed antivenom production and quality control measures and special consideration was given to the current crisis in antivenom production and supply in sub-Saharan Africa. The importance of snake bite and scorpion stings as public health issues was re-emphasised. The majority of commercial antivenoms are raised against snake or scorpion venoms.The review of antivenom production methods indicated that the vast majority of commercial antivenoms were still produced by traditional technology in horses, although some antisera were raised in sheep and rabbits. Methods used for plasma fractionation included salt and heat coagulation, caprylic acid stabilization or ion exchange chromatography, as well as immunoglobulin digestion with pepsin to produce F(ab′)2 or with papain to produce Fab fragments. The meeting agreed that there was much room for improving the production, quality control and safety profile of these products and that lessons could be learnt from the experience gained with the preparation of human immunoglobulins. Many basic assumptions, such as the need to remove Fc fragments by enzyme digestion and to freeze–dry antivenom preparations, required critical re-examination and more attention should be given to clinical trials as a means of assessing efficacy and safety and of defining the average initial dose. The Workshop also discussed concerns about the risks of transmitting infectious agents to humans via animal blood products, especially those posed by viruses or prions and it was agreed that this aspect needed attention. However, there was no documented or even suspected example of this ever having occurred in the case of antivenom treatment.Current WHO Requirements for the production and control of antivenoms and for immune sera of animal origin date from the late 1960s. The Workshop recommended that these be updated to take account of the progress that had taken place in the production and quality control of biologicals in recent years. In addition, the Workshop discussed the need for better standardization of both the venoms and antivenoms, but concluded that international standards and reference materials were not appropriate in the antivenom field due to the considerable variation in venom characteristics from the same species from region to region. Instead, it was recommended that national or regional standards be prepared and used. [Copyright &y& Elsevier]

Treatment with Semple or suckling mouse brain rabies vaccines persists in many countries of Asia, Africa and South America. Its replacement depends on the immediate accessibility of effective affordable alternative treatment with tissue culture vaccines (TCVs). The use of the expensive European TCVs has been possible in Asia by means of economical intradermal (ID) post-exposure vaccine regimens. Implementation of this effective economical treatment has been delayed by the complexity and inconvenience of the regimens, and the reluctance to change prophylaxis against a fatal disease. Up to now, the ID regimens have been used only where passive immunisation with rabies immune globulin (RIG) is usually available. Rabies deaths despite optimal vaccine treatment have been attributed to lack of RIG. The ID regimens might soon be promoted in areas where RIG is not even available for severe exposure. It is therefore vital that economical vaccine regimens should be used which induce protective immunity rapidly.Improvements in rabies PET in developing countries could be made by: (i) publicising the urgency and efficacy of wound cleaning; (ii) facilitating the replacement of nervous tissue vaccines by economical ID treatment with TCVs; (iii) using an ID regimen with a large dose of vaccine on the first day of treatment especially when no RIG is available; and (iv) promoting pre-exposure prophylaxis to eliminate the need for RIG and provide better rabies prophylaxis. [Copyright &y& Elsevier]

Two cases of mycotic aneurysms of the left anterior descending coronary artery in patients with fungal prosthetic valve endocarditis are reported. One was managed with exclusion and interposition graft, and the other was managed by aneurysm excision, wide debridement, and distal bypass. The current literature and management strategies are reviewed. [Copyright &y& Elsevier]

Clinical research has always been a part of transplantation; however, with breakthroughs in cellular immunotherapy (CI), such as CAR T-cell and T-cell receptor therapy, the number of clinical research trials in this area has rapidly increased. At our center, there are currently 38 open CI trials with 15 more opening in the next few months. These trials are multifaceted and complex requiring intensive coordination, development of workflows, diligent nursing care, and additional education across departments and treatment settings. To safely and efficiently run a trial, a study start up process must be in place. Nursing leadership including managers, a CNS, and an education specialist, played an integral role in the interdisciplinary team collaboration required for conducting successful clinical trials. Nursing leadership began attending site initiation visits and implementation meetings to gain insight into each new clinical trial and develop patient and nursing workflows. Nursing leadership also assists the clinical trial coordinators (CTC) with the creation of a "quick reference" protocol summary education sheet that is used to assist with caring for the patient. A bi-weekly clinical trials operational meeting, attended by nursing leadership and CTCs, was initiated to discuss problems or issues with current trials. To address knowledge deficits related to CI and specific clinical trials, existing education materials were updated and additional education was created as needed. The unit-based orientation was also modified to include content on CI and clinical trials. Prior to opening, each new clinical trial now undergoes a standardized process to determine appropriate workflows, outline the patient journey, and identify education needs. Nursing is involved in every step of the process, which has positively impacted the safety and efficacy of the trials. Although it is an ever-evolving work in progress, the clinical trial process at our institution has allowed for the successful implementation of numerous CI clinical trials. Our processes have been replicated by the clinical trial industry as a model for other organizations. Nursing participation and leadership is essential for successful clinical trial implementation and safe patient care. [ABSTRACT FROM AUTHOR]

The 12 Arab countries of the Middle East are inhabited by 21 species of terrestrial venomous snakes of varying medical importance. This review considers these species, consisting of 16 viperids, 3 elapids and 2 atractaspidines. Iraq, Jordan, Lebanon, Oman, Saudi Arabia, and Yemen report the largest numbers of snakebites and envenomings. Accessible literature in English and Arabic on venomous snakes and snakebites and available antivenoms is reviewed. Clinical effects include potentially misleading symptoms attributable to anxiety and traditional pre-hospital treatments. • This review is intended to serve public health providers in the Arab countries in the Middle East. • The epidemiology and clinical symptoms as well as treatment with antivenoms is discussed. • Antivenoms used is the Arab countries is revised based on current practices. [ABSTRACT FROM AUTHOR]

In the 1890s, hyperimmune sera proved effective in animals against challenge by the snake venom against which they had been raised. They were first used, apparently successfully, in a human patient in about 1895. Since then, antivenoms have become accepted as the only reliable specific treatment for snake-bite envenoming. Despite decades of accumulated clinical experience and a number of published randomized comparative and observational studies, the clinical effectiveness and safety of some antivenoms remain open to question, due to a lack of robust randomized controlled trial data. Antivenoms in some poorly regulated markets may have high rates of potentially fatal adverse effects and their use must be balanced by demonstrable effectiveness. Even those manufactured to strict regulatory requirements may pose a rare risk of severe adverse reactions. Most antivenoms currently marketed around the world were registered without first being studied clinically. There is increasing pressure to subject antivenoms, even those that are long-established, to the same protocols of rigorous pre-clinical and clinical assessment that are standard regulatory requirements for other drugs. Conventional clinical testing progresses through Phases I, II, III to IV. Most authorities consider antivenoms too dangerous to be used in Phase I studies in healthy volunteers. An alternative method for preliminary estimation of safety, dose-finding and effectiveness, is proposed - the “3 + 3” dose escalation or de-escalation design, in volunteer patients, as used in oncology to test cytotoxic drugs. Antivenoms are so widely used and well trusted, that there are few ethical justifications for placebo controls. However, placebo might be ethically justified if there were no proven effective treatment and or if withholding or delaying treatment posed acceptably negligible risks to the participants. Antivenom trials are most urgently needed in low-to middle-income countries where there are many practical, logistical and funding challenges. Basic requirements for clinical trials include identification of the biting species of snake in every case; the use of objective, clinically-relevant endpoints, such as restoration of blood coagulability; definition of inclusion, exclusion and withdrawal criteria; assurance of antivenom safety; ethical considerations; inclusion of one or more control (comparator) groups; and analysis based on intention to treat. The highest quality evidence comes from Phase II and larger Phase III studies that have been designed as statistically powerful, randomized, controlled trials (RCTs), ideally with blinding of patients and investigators to avoid bias. Because of the challenges to carrying out clinical trials of antivenoms, Phase IV trials (post-marketing surveillance) are potentially more important and useful than for most other drugs. [ABSTRACT FROM AUTHOR]