Imported malaria: key messages in an era of elimination.

Despite concerted efforts to eliminate malaria, it remains a major global cause of morbidity and mortality with over 200 million annual cases. Significant gains have been made, with the annual global malaria incidence and mortality halving over the past twenty years, using tools such as long-lasting insecticide-treated bed nets and artemisinin-based therapies. Malaria is also a significant cause of life-threatening imported infection in the UK. It is vital for front line clinical staff involved in the assessment of acutely ill patients to be aware of the need for early diagnostic testing, malaria epidemiology, markers of severe infection and developments in antimalarial treatments to optimise patient management. The difference between a good and poor outcome is early diagnosis and treatment. Many of the challenges faced in the quest for global eradication, such as availability of appropriate diagnostic tests, and drug and insecticide resistance could also have future implications for imported malaria

Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy.

The OVIVA study demonstrated noninferiority for managing bone and joint infections (BJIs) with oral antibiotics. We report that 79.7% of OPAT patients being treated for BJIs at our center would be eligible for oral antibiotics, saving a median (IQR) 19.5 IV-antibiotic days (8.5-37) and GBP 1234 (569-2594) per patient

Demographics and Outcomes of Initial Phase of COVID-19 Medicines Delivery Units Across 4 UK Centers During Peak B1.1.529 Omicron Epidemic: A Service Evaluation

Background: COVID-19 medicines delivery units (CMDU) were established in late December 2021 to deliver early antiviral therapy to patients classified as at risk with the aim of preventing hospitalization. Methods: We performed a service evaluation at 4 CMDUs in England. We assessed demographics and triage outcomes of CMDU referral, uptake of antiviral therapy, and the rate of subsequent hospitalizations within 2 weeks of CMDU referral. Results: Over a 3-week period, 4788 patients were referred and 3989 were ultimately assessed by a CMDU. Overall, 832 of the patients referred (17%) were judged eligible for treatment and 628 (13%) were ultimately prescribed an antiviral agent. The overall rate of admission within 14 days was 1%. Patients who were admitted were significantly older than those who did not require hospitalization. Of patients prescribed molnupiravir and sotrovimab, 1.8% and 3.2%, respectively, were admitted. Conclusions: There was a high volume of referrals to CMDU service during the initial surge of the Omicron wave in the United Kingdom. A minority of patients were judged to be eligible for therapy. In a highly vaccinated population, the overall hospitalization rate was low

Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: an observational cohort study.

The number of proposed prognostic models for coronavirus disease 2019 (COVID-19) is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation.We independently externally validated the performance of candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at the time of admission. We assessed discrimination, calibration and net benefit, compared to the default strategies of treating all and no patients, and against the most discriminating predictors in univariable analyses.We tested 22 candidate prognostic models among 411 participants with COVID-19, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. Highest areas under receiver operating characteristic (AUROC) curves were achieved by the NEWS2 score for prediction of deterioration over 24 h (0.78, 95% CI 0.73-0.83), and a novel model for prediction of deterioration <14 days from admission (0.78, 95% CI 0.74-0.82). The most discriminating univariable predictors were admission oxygen saturation on room air for in-hospital deterioration (AUROC 0.76, 95% CI 0.71-0.81), and age for in-hospital mortality (AUROC 0.76, 95% CI 0.71-0.81). No prognostic model demonstrated consistently higher net benefit than these univariable predictors, across a range of threshold probabilities.Admission oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated here offered incremental value for patient stratification to these univariable predictors

Assessment of MpoxPlex, a high-throughput and multiplexed immunoassay:a diagnostic accuracy study

Background: In May, 2022, the first global outbreak of mpox (formerly known as monkeypox) occurred. In response, public health agencies in the UK have made smallpox vaccines available to individuals at the highest risk of infection. With mpox cases still being detected globally, novel tools are required to aid with diagnosis, serosurveillance, and the evaluation of immune responses following infection and immunisation with current and new vaccine candidates. Here, we describe the development of a multiplexed immunoassay, MpoxPlex, able to measure IgG responses to 12 Orthopoxvirus antigens concurrently and distinguish between responses to infection and vaccination. Methods: Using the Luminex (DiaSorin, Saluggia, Italy) platform, antibody responses to vaccinia virus (VACV) antigens B5, A27, and A33 and monkeypox virus (MPXV) antigens E8, B6, B2, M1, A27, A35, H3, A29, and A5 were assessed in serum from individuals after MPXV infection (n=24) and after vaccination (n=75) with modified VACV Ankara-Bavarian Nordic. Assay characteristics and cutoffs were calculated by fitting receiver operating characteristic curves to the median fluorescence intensities of these positive samples and negative samples that were run alongside (n=435). P values were calculated using non-parametric Mann–Whitney, Kruskal–Wallis, and Dunn's multiple comparisons tests. Findings: Using the results from a combination of eight antigens, we were able to distinguish samples as either post-vaccination or post-infection from negative samples with a sensitivity of 98% and a specificity of 95%. IgG responses to MPXV antigen A27 were able to distinguish post-MPXV infection with a sensitivity of 88% and a specificity of 97%. VACV antigen A27 and MPXV antigens A29 and A5 provided little diagnostic advantage. Interpretation: With additional benefits over current serological assays, we believe this assay will provide substantial insight into the current global outbreak of mpox. MpoxPlex shows use for both serosurveillance and immunological studies of vaccination and infection. Funding: Grant-in-aid funding to the Emerging Pathogen Serology Group at Porton Down, UK Health Security Agency

Comparison of new and emerging SARS-CoV-2 variant transmissibility through active contact testing. A comparative cross-sectional household seroprevalence study

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding

Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.

OBJECTIVE: Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use. METHODS: We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected. RESULTS: 196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%. CONCLUSIONS: Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting

Experience of a novel community testing programme for COVID-19 in London: Lessons learnt

We describe the London community testing programme developed for COVID-19, audit its effectiveness and report patient acceptability and patient adherence to isolation guidance, based upon a survey conducted with participants. Any patients meeting the Public Health England (PHE) case definition for COVID-19 who did not require hospital admission were eligible for community testing. 2,053 patients with suspected COVID-19 were tested in the community between January and March 2020. Of those tested, 75 (3.6%) were positive. 88% of patients that completed a patient survey felt safe and 82% agreed that community testing was preferable to hospital admission. 97% were able to remain within their own home during the isolation period but just 41% were able to reliably isolate from other members of their household. The London community testing programme allowed widespread testing for COVID-19 while minimising patient transport, hospital admissions and staff exposures. Community testing was acceptable to patients and preferable to admission to hospital. Patients were able to reliably isolate in their home but not from household contacts. The authors believe in the importance, feasibility and acceptability of community testing for COVID-19 as a part of a package of interventions to mitigate a second wave of infection

Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021

Monkeypox is a rare viral zoonotic disease. The causing virus belongs to the Orthopoxvirus genus that includes variola virus (the cause of smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus. There are two distinct clades of monkeypox virus—Central African and West African. The first human cases were identified in the Democratic Republic of Congo in 1970 [1]. Outside of Africa, cases of human monkeypox infections have been documented in four countries: four cases the United Kingdom (UK) in 2018/2019, one case in Israel in 2018 and one case in Singapore in 2019 [2], 47 cases in the United States (US) in 2003 and one in 2021 [3]. We report on a family cluster of three recent cases of monkeypox in the UK associated with travel from Nigeria

First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5-17 months old infants and children

Background Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in United Kingdom adult Phase IIa sporozoite challenge studies (approximately 20–25% sterile protection with similar numbers showing clear delay in time to patency), and greater point efficacy in a trial in Kenyan adults. Methodology We conducted the first Phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63 MVA ME-TRAP in 700 healthy malaria exposed children aged 5–17 months in a highly endemic malaria transmission area of Burkina Faso. Results ChAd63 MVA ME-TRAP was shown to be safe and immunogenic but induced only moderate T cell responses (median 326 SFU/106 PBMC (95% CI 290–387)) many fold lower than in previous trials. No significant efficacy was observed against clinical malaria during the follow up period, with efficacy against the primary endpoint estimate by proportional analysis being 13.8% (95%CI -42.4 to 47.9) at sixth month post MVA ME-TRAP and 3.1% (95%CI -15.0 to 18.3; p = 0.72) by Cox regression. Conclusions This study has confirmed ChAd63 MVA ME-TRAP is a safe and immunogenic vaccine regimen in children and infants with prior exposure to malaria. But no significant protective efficacy was observed in this very highly malaria-endemic setting