Artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance. METHODS: In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance. RESULTS: We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate-mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. CONCLUSIONS: P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.

Factors associated with early uptake of COVID-19 vaccination among healthcare workers in Azerbaijan, 2021.

INTRODUCTION: We evaluated uptake and factors associated with COVID-19 vaccination among health workers (HWs) in Azerbaijan. RESULTS: Among 1575 HWs, 73% had received at least one dose, and 67% received two doses; all received CoronaVac. Factors associated with vaccination uptake included no previous COVID-19 infection, older age, belief in the vaccine's safety, previous vaccination for influenza, having patient-facing roles and good or excellent health by self-assessment. CONCLUSION: These findings could inform strategies to increase vaccination uptake as the campaign continues

Evidence for overwintering and autochthonous transmission of Usutu virus to wild birds following its redetection in the United Kingdom

Usutu virus (USUV) is an emerging zoonotic arbovirus in Europe, where it primarily impacts Eurasian blackbirds (Turdus merula). For mosquito-borne viruses to persist in temperate areas, transovarial transmission in vectors or overwintering in either hosts or diapausing vectors must occur to facilitate autochthonous transmission. We undertook surveillance of hosts and vectors in 2021 to elucidate whether USUV had overwintered in the United Kingdom (UK) following its initial detection there in 2020. From 175 dead bird submissions, we detected 1 case of USUV infection, in a blackbird, from which a full USUV genome was derived. Using a molecular clock analysis, we demonstrate that the 2021 detection shared a most recent common ancestor with the 2020 Greater London, UK, USUV sequence. In addition, we identified USUV-specific neutralizing antibodies in 10 out of 86 serum samples taken from captive birds at the index site, demonstrating in situ cryptic infection and potential sustained transmission. However, from 4966 mosquitoes, we detected no USUV RNA suggesting that prevalence in the vector community was absent or low during sampling. Combined, these results suggest that USUV overwintered in the UK, thus providing empirical evidence for the continued northward expansion of this vector-borne viral disease. Currently, our detection indicates geographically restricted virus persistence. Further detections over time will be required to demonstrate long-term establishment. It remains unclear whether the UK, and by extension other high-latitude regions, can support endemic USUV infection

Clinical Application of Real-Time PCR to Screening Critically Ill and Emergency-Care Surgical Patients for Methicillin-Resistant Staphylococcus aureus: a Quantitative Analytical Study▿ †

The clinical utility of real-time PCR screening assays for methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) colonization is constrained by the predictive values of their results: as MRSA prevalence falls, the assay's positive predictive value (PPV) drops, and a rising proportion of positive PCR assays will not be confirmed by culture. We provide a quantitative analysis of universal PCR screening of critical care and emergency surgical patients using the BD GeneOhm MRSA PCR system, involving 3,294 assays over six months. A total of 248 PCR assays (7.7%) were positive; however, 88 failed to be confirmed by culture, giving a PPV of 65%. Multivariate analysis was performed to compare PCR-positive culture-positive (P+C+) and PCR-positive culture-negative (P+C−) assays. P+C− results were positively associated with a history of methicillin-sensitive Staphylococcus aureus infection or colonization (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.32 to 7.54) and high PCR thresholds of signal intensity, indicative of a low concentration of target DNA (OR, 1.19 per cycle; 95% CI, 1.11 to 1.26). P+C− results were negatively associated with a history of MRSA infection or colonization (OR, 0.19; 95% CI, 0.09 to 0.42) and male sex (OR, 0.40; 95% CI, 0.20 to 0.81). P+C+ patients were significantly more likely to have subsequent positive MRSA culture assays and microbiological evidence of clinical MRSA infection. The risk of subsequent MRSA infection in P+C− patients was not significantly different from that in case-matched PCR-negative controls. We conclude that, given the low PPV and poor correlation between a PCR-positive assay and the clinical outcome, it would be prudent to await culture confirmation before altering infection control measures on the basis of a positive PCR result

Clinical frailty as a key characteristic of the patient population of the NHS Nightingale North West COVID-19 temporary emergency field hospital: cohort study April to June 2020

OBJECTIVES: COVID-19 temporary emergency ‘field’ hospitals have been established in the UK to support the surge capacity of the National Health Service while protecting the community from onward infection. We described the population of one such hospital and investigated the impact of frailty on clinical outcomes. DESIGN: Cohort study. SETTING: NHS Nightingale Hospital North West, April–June 2020. PARTICIPANTS: All in-patients with COVID-19. MAIN OUTCOME MEASURES: Mortality and duration of admission. METHODS: We analysed factors associated with mortality using logistic regression and admission duration using Cox's regression, and described trends in frailty prevalence over time using linear regression. RESULTS: A total of 104 COVID-19 patients were admitted, 74% with moderate-to-severe frailty (clinical frailty score, CFS > 5). A total of 84 were discharged, 14 transferred to other hospitals, and six died on site. High C-reactive protein (CRP) > 50 mg/dL predicted 30-day mortality (adjusted odds ratio 11.9, 95%CI 3.2–51.5, p  5 had a 10-day median admission, versus 7-day for CFS ≤ 5 and half the likelihood of discharge on a given day (adjusted hazard ratio 0.51, 95%CI 0.29–0.92, p  =  0.024). CRP > 50 mg/dL and hospital-associated COVID-19 also predicted admission duration. As more frail patients had a lower rate of discharge, prevalence of CFS > 5 increased from 64% initially to 90% in the final week (non-zero slope p < 0.001). Conclusions: The NNW population was characterized by high levels of frailty, which increased over the course of the hospital's operation, with subsequent operational implications. Identifying and responding to the needs of this population, and acknowledging the risks of this unusual clinical context, helped the hospital to keep patients safe

Clinical management and impact of scarlet fever in the modern era: findings from a cross-sectional study of cases in London, 2018-2019

Objectives: In response to increasing incidence of scarlet fever and wider outbreaks of group A streptococcal infections in London, we aimed to characterise the epidemiology, symptoms, management and consequences of scarlet fever, and to identify factors associated with delayed diagnosis. Design and setting: Cross-sectional community-based study of children with scarlet fever notified to London’s three Health Protection Teams, 2018–2019. Participants: From 2575 directly invited notified cases plus invitations via parental networks at 410 schools/nurseries with notified outbreaks of confirmed/probable scarlet fever, we received 477 responses (19% of those directly invited), of which 412 met the case definition. Median age was 4 years (range &lt;1 to 16), 48% were female, and 70% were of white ethnicity. Outcome measures: Preplanned measures included quantitative description of case demographics, symptoms, care-seeking, and clinical, social, and economic impact on cases and households. After survey completion, secondary analyses of factors associated with delayed diagnosis (by logistic regression) and consequences of delayed diagnosis (by Cox’s regression), and qualitative analysis of free text comments were added. Results: Rash was reported for 89% of cases, but followed onset of other symptoms for 71%, with a median 1-day delay. Pattern of onset varied with age: sore throat was more common at onset among children 5 years and older (OR3.1, 95% CI 1.9 to 5.0). At first consultation, for 28%, scarlet fever was not considered: in these cases, symptoms were frequently attributed to viral infection (60%, 64/106). Delay in diagnosis beyond first consultation occurred more frequently among children aged 5+ who presented with sore throat (OR 2.8 vs 5+without sore throat; 95% CI 1.3 to 5.8). Cases with delayed diagnosis took, on average, 1 day longer to return to baseline activities. Conclusions: Scarlet fever may be initially overlooked, especially among older children presenting with sore throat. Raising awareness among carers and practitioners may aid identification and timely treatment

High frequency of paediatric facial nerve palsy due to Lyme disease in a geographically endemic region

Introduction: Idiopathic facial nerve palsy (FNP) is an uncommon but important presentation in children, with Lyme disease known to be a common cause. The UK county of Hampshire is a high incidence area of Lyme disease. We conducted a retrospective review of the investigation and management of paediatric FNP at a large University hospital, including serologic testing and treatment of Lyme disease.Methods: We conducted a retrospective chart review of children under 18 presenting between January 1st 2010 and December 31st 2017 with a diagnosis of FNP. Patients with clear non-Lyme aetiology at presentation were excluded. Data was collected on demographics, initial presentation, investigations including Lyme serology, and management.Results: A total of 93 children were identified, with an even proportion of male to female and median age 9.3 years (IQR 4.6-12 years). A history of rash was present in 5.4%, tick bite in 14% and recent travel to, or residence in the New Forest in 22.6%. Lyme serology was performed in 81.7% of patients, of which 29% were positive. Antibiotics were prescribed for 73.1% of patients, oral steroids for 44% and aciclovir for 17.2%.Conclusion: Lyme disease is a significant cause of FNP in this endemic area of the UK, and there was a large degree of variability in management prior to national guideline publication. Areas with endemic Lyme disease should consider introducing local guidelines supporting routine investigation and management for FNP, including empiric treatment for Lyme disease in accordance with NICE guidelines to improve care and reduce variability

Data from: The relationship between poverty and healthcare seeking among patients hospitalized with acute febrile illnesses in Chittagong, Bangladesh

Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0°C and symptoms of up to 14 days’ duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative’s multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)—5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare