Haemorrhagic fever with renal syndrome (HFRS), a rodent-borne disease, is a major public health concern in both developed and developing countries. China is the most severe endemic country in the world, constituting 90% of the cases. Although the incidence of HFRS has substantively decreased in most areas of China, HFRS has rebounded remarkably in some epidemic areas. Xuancheng is one of these areas. In this study, we collected the case data reported recently in Xuancheng and designed a 1:3 case−control study. The Chi-square test, univariate and multivariate logistic regression analysis were performed. In all cases, farmers made up the highest proportion of occupations. And there were 20 variables with statistical significance including indoor hygienic conditions; the surrounding environment; whether bitten by rats at work and other criteria. In addition, exposure to rodents and rats bites is a high-risk factor for HFRS. Rodent density was calculated at 20.9% (159/760), the virus carrier rate was 9.4% (15/159) and the index of rats with a virus was about 2.0%. Exposure to rodents and insect bites is also high-risk factors for HFRS among local residents in Xuancheng. More importantly, during the flood years, the increased density of rodents led to an increased risk of human exposure to rodents. As our statistical analysis proves, targeted strategies should be developed and implemented to reduce the incidence of local diseases in the future.

Several studies report norovirus as the new leading cause of severe gastroenteritis in children after the global introduction of rotavirus vaccines. Burkina Faso introduced general rotavirus vaccination with the oral pentavalent vaccine RotaTeq in November 2013 and quickly reached a vaccine coverage of >90%. This study describes detection rates, clinical profiles and the molecular epidemiology of norovirus and rotavirus infections in 146 children aged <5 years with severe acute gastroenteritis in Ouagadougou, consecutively enrolled from a hospital between January 2015 and December 2015. Virus detection was performed with an antigen test or real-time polymerase chain reaction (PCR) and genotyping was performed by nucleotide sequencing or multiplex PCR. Rotavirus was found in 14% and norovirus in 20% of faecal samples. Norovirus infection was significantly more associated with severe dehydration compared to rotavirus (P < 0.001). Among genotyped norovirus samples 48% (12/25) belonged to GII.4 which caused significantly more diarrhoeal episodes than non-GII.4 genotypes (P = 0.01). The most common rotavirus genotypes were G2P[4] (30%), G12P[6] (25%) and G12P[8] (20%). Fifty percent of the rotavirus positive children were infected with fully or partly heterotypic strains. In conclusion, this study found a higher proportion of norovirus causing more severe symptoms in children with diarrhoea in Burkina Faso after the introduction of rotavirus vaccination.

A recently developed pneumonia caused by SARS-CoV-2 has quickly spread across the world. Unfortunately, a simplified risk score that could easily be used in primary care or general practice settings has not been developed. The objective of this study is to identify a simplified risk score that could easily be used to quickly triage severe COVID-19 patients. All severe and critical adult patients with laboratory-confirmed COVID-19 on the West campus of Union Hospital, Wuhan, China, from 28 January 2020 to 29 February 2020 were included in this study. Clinical data and laboratory results were obtained. CURB-65 pneumonia score was calculated. Univariate logistic regressions were applied to explore risk factors associated with in-hospital death. We used the receiver operating characteristic curve and multivariate COX-PH model to analyse risk factors for in-hospital death. A total of 74 patients (31 died, 43 survived) were finally included in the study. We observed that compared with survivors, non-survivors were older and illustrated higher respiratory rate, neutrophil-to-lymphocyte ratio, D-dimer and lactate dehydrogenase (LDH), but lower SpO2 as well as impaired liver function, especially synthesis function. CURB-65 showed good performance for predicting in-hospital death (area under curve 0.81, 95% confidence interval (CI) 0.71–0.91). CURB-65 ⩾ 2 may serve as a cut-off value for prediction of in-hospital death in severe patients with COVID-19 (sensitivity 68%, specificity 81%, F1 score 0.7). CURB-65 (hazard ratio (HR) 1.61; 95% CI 1.05–2.46), LDH (HR 1.003; 95% CI 1.001–1.004) and albumin (HR 0.9; 95% CI 0.81–1) were risk factors for in-hospital death in severe patients with COVID-19. Our study indicates CURB-65 may serve as a useful prognostic marker in COVID-19 patients, which could be used to quickly triage severe patients in primary care or general practice settings.

Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case-fatality rate that is caused by infection with the SFTS virus (SFTSV). Five electronic databases were systematically searched to identify relevant articles published from 1 January 2011 to 1 December 2019. The pooled rates with 95% confidence interval (CI) were calculated by a fixed-effect or random-effect model analysis. The results showed that 92 articles were included in this meta-analysis. For the confirmed SFTS cases, the case-fatality rate was 0.15 (95% CI 0.11, 0.18). Two hundred and ninety-six of 1384 SFTS patients indicated that they had been bitten by ticks and the biting rate was 0.21 (95% CI 0.16, 0.26). The overall pooled seroprevalence of SFTSV antibodies among the healthy population was 0.04 (95% CI 0.03, 0.05). For the overall seroprevalence of SFTSV in animals, the seroprevalence of SFTSV was 0.25 (95% CI 0.20, 0.29). The infection rate of SFTSV in ticks was 0.08 (95% CI 0.05, 0.11). In conclusion, ticks can serve as transmitting vectors of SFTSVs and reservoir hosts. Animals can be infected by tick bites, and as a reservoir host, SFTSV circulates continuously between animals and ticks in nature. Humans are infected by tick bites and direct contact with patient secretions.

The mortality of coronavirus disease 2019 (COVID-19) differs between countries and regions. This study aimed to clarify the clinical characteristics of imported and second-generation cases in Shaanxi. This study included 134 COVID-19 cases in Shaanxi outside Wuhan. Clinical data were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. In total, 34.3% of the 134 patients were severe cases, 11.2% had complications. As of 7 March 2020, 91.8% patients were discharged and one patient (0.7%) died. Age, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, direct bilirubin, lactate dehydrogenase and hydroxybutyrate dehydrogenase showed difference between severe and no-severe cases (all P < 0.05). Baseline lymphocyte count was higher in survived patients than in non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The interleukin-6 (IL-6) level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest computed tomography images in 51.5% of the pneumonia cases. Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.

Tuberculosis (TB) is one of the top 10 leading causes of morbidity and mortality worldwide [1]. In 2017, approximately 10 million people were infected with TB and 1.3 million patients faced mortality [1]. Patients with active TB can infect up to 10–15 people over a year. There is a greater risk of transmission in overcrowded areas with limited air ventilation including large family units, prisons and slums [1, 2]. Without proper diagnosis and treatment, roughly 45% of non-HIV positive TB patients face mortality [1]. With the help of global organizations and national TB treatment and control programmes, the global incidence of TB is declining by approximately 2% each year [1]. The World Health Organization (WHO) TB-strategy aims to end the TB epidemic and encourages partners to fund national TB programmes to improve diagnosis and treatment of TB. The goal is to ultimately decrease death rates by 90% and decrease incidence rates by 80% [1]. To achieve these goals, the decline in TB incidence needs to reach approximately 4–5% per year [1]. The WHO 2018 TB report identified multidrug resistant TB (MDR-TB) as the leading factor hindering that goal [1]. The incidence and spread of MDR-TB has drastically increased, where approximately 558 000 new cases of MDR-TB were diagnosed in 2017 causing more than 230 000 deaths globally [1]. MDR-TB is identified by resistance to the two most powerful anti-TB treatment drugs including isoniazid and rifampicin [3]. Patients with MDR-TB are required to start second-line anti-TB drugs (SLDs), which are limited, expensive, less effective and more toxic [1,2]. Therapy duration is one of the major limitations of second-line treatments, which may require up to two years of consistent use. Since TB affects mostly developing countries, long treatment durations and associated costs become a major challenge. In 2015, 15% of new TB cases were reported as MDR-TB, which drastically increased to 24% by 2017 [1]. Even with significant improvements in molecular tests and diagnostic methods, MDR-TB is still on the rise where the success rate of treatments is between 50 and 60% [1]. Additional characteristics including socioeconomic and sociocultural factors need to be considered when targeting and treating patients with MDR-TB.

The pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a serious global public health issue. Since the start of the outbreak, the importance of hand-hygiene and respiratory protection to prevent the spread of the virus has been the prime focus for infection control. Health regulatory organisations have produced guidelines for the formulation of hand sanitisers to the manufacturing industries. This review summarises the studies on alcohol-based hand sanitisers and their disinfectant activity against SARS-CoV-2 and related viruses. The literature shows that the type and concentration of alcohol, formulation and nature of product, presence of excipients, applied volume, contact time and viral contamination load are critical factors that determine the effectiveness of hand sanitisers.

In Spain, the epidemic curve caused by COVID-19 has reached its peak in the last days of March. The implementation of the blockade derived from the declaration of the state of alarm on 14th March has raised a discussion on how and when to deal with the unblocking. In this paper, we intend to add information that may help by using epidemic simulation techniques with stochastic individual contact models and several extensions.

Earlier reports revealed oxysterol metabolites of Opisthorchis spp. liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here, we employed liquid chromatography-mass spectrometry to investigate, compare and contrast spectrograms of soluble extracts from Fasciola hepatica adult worms from bile ducts of cattle with those from O. viverrini and O.felineus from experimentally infected hamsters. F. hepatica and Opisthorchis spp. shared common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of F. hepatica included far fewer compounds than Opisthorchis species. These findings support the postulate that parasitic oxysterol-like metabolites could be related to carcinogenesis associated to infection and they point to a molecular basis for the differences among major groups of liver flukes concerning infection-induced malignancy.

Chordoma is a rare bone cancer for which there are no approved drugs. Surgery is the principle treatment but complete resection can be challenging due to the location of the tumours in the spine and therefore finding an effective drug treatment is a pressing unmet clinical need. A major recent study identified the transcription factor Brachyury as the primary vulnerability and drug target in chordoma. Previously, all-trans retinoic acid (ATRA) has been shown to negatively influence expression of the Brachyury gene, TBXT. Here we extend this finding and demonstrate that ATRA lowers Brachyury protein levels in chordoma cells and reduces proliferation of the chordoma cell line U-CH1 as well as causing loss of distinctive chordoma cell morphology. ATRA is available as a generic drug and is the first line treatment for acute promyelocytic leukaemia (APL). This study implies ATRA could have therapeutic value if repurposed for chordoma.

Bollobás and Nikiforov (J. Combin. Theory Ser. B. 97 (2007) 859–865) conjectured the following. If G is a Kr+1-free graph on at least r+1 vertices and m edges, then ${\rm{\lambda }}_1^2(G) + {\rm{\lambda }}_2^2(G) \le (r - 1)/r \cdot 2m$, where λ1 (G)and λ2 (G) are the largest and the second largest eigenvalues of the adjacency matrix A(G), respectively. In this paper we confirm the conjecture in the case r=2, by using tools from doubly stochastic matrix theory, and also characterize all families of extremal graphs. Motivated by classic theorems due to Erdös and Nosal respectively, we prove that every non-bipartite graph of order and size contains a triangle if one of the following is true: (i) ${{\rm{\lambda }}_1}(G) \ge \sqrt {m - 1} $ and $G \ne {C_5} \cup (n - 5){K_1}$, and (ii) ${{\rm{\lambda }}_1}(G) \ge {{\rm{\lambda }}_1}(S({K_{[(n - 1)/2],[(n - 1)/2]}}))$ and $G \ne S({K_{[(n - 1)/2],[(n - 1)/2]}})$, where $S({K_{[(n - 1)/2],[(n - 1)/2]}})$ is obtained from ${K_{[(n - 1)/2],[(n - 1)/2]}}$ by subdividing an edge. Both conditions are best possible. We conclude this paper with some open problems.

It has been speculated that some drugs can be used against SARS-CoV-2. As for antiretrovirals, the follow-up of pre-exposure prophylaxis (PrEP) users during the coronavirus disease 2019 (COVID-19) outbreak may help to understand the potential protective effect of PrEP against SARS-CoV-2. We aimed to identify associations between oral PrEP use and COVID-19-related symptoms self-reporting. Phone call interviews or digital investigation (through WhatsApp® or e-mail) about oral PrEP regular use, social distancing, exposure to suspected or confirmed cases of SARS-CoV-2 infection and COVID-19-related symptoms. Among 108 individuals, the majority were cisgender, white and gay men. Although most of the individuals engaged in social distancing (68.52%), they kept on taking PrEP (75.93%). Few people have had contact with suspected or confirmed cases of COVID-19 (12.04%), but some had COVID-19-related symptoms the month before the interview (27.78%) including rhinorrheoa (56.67%), cough (53.33%), asthaenia (50.00%) and headache (43.33%). Also, oral PrEP was associated with lower self-reporting COVID-19-symptoms (OR 0.26, 95% CI 0.07–0.96, P = 0.04; h = 0.92) even after controlling confounders as social distancing, age, body-mass index and morbidities . In our sample, the regular use of oral PrEP was associated with lower self-reporting of COVID-19-related symptoms during the outbreak in São Paulo, Brazil.

We consider nonparametric identification and estimation of pricing kernels, or equivalently of marginal utility functions up to scale, in consumption-based asset pricing Euler equations. Ours is the first paper to prove nonparametric identification of Euler equations under low level conditions (without imposing functional restrictions or just assuming completeness). We also propose a novel nonparametric estimator based on our identification analysis, which combines standard kernel estimation with the computation of a matrix eigenvector problem. Our estimator avoids the ill-posed inverse issues associated with nonparametric instrumental variables estimators. We derive limiting distributions for our estimator and for relevant associated functionals. A Monte Carlo experiment shows a satisfactory finite sample performance for our estimators.

Gonorrhoea cases in women have been rising in Australia in the 2010s but the cause of the increase is not well understood. This cross-sectional study aimed to describe the characteristics of genital gonorrhoea infection in women attending the Melbourne Sexual Health Centre, Australia. Gonorrhoea cases were diagnosed by nucleic acid amplification test (NAAT) and/or culture. Genitourinary specimens were obtained in 12 869 clinic visits in women aged 16 years or above between August 2017 and August 2018. Genital gonorrhoea was detected in 142 (1.1%) of the visits. Almost half of the cases were asymptomatic, 47.9% [95% confidence interval (CI) 39.8–56.1%]; yellow, green or pus-like vaginal discharge was present in 11.3% (95% CI 7.0–17.6%) and other genital symptoms in 40.8% (95% CI 33.1–49.1%) of the cases. The mean time between last sexual contact and onset of symptoms was 7.3 days and between the onset of symptoms to presentation to the clinic was 12.1 days. Half of the cases of genital gonorrhoea among women are asymptomatic and these cases would have been missed by testing of only symptomatic women. Further epidemiological and behavioural research is required to understand the temporal changes in sexual practices among women in Australia.

Data on the possibility of transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the provision of chronic haemodialysis, which often entails many person-to-person contacts, are lacking. We report a follow-up of the in-centre contacts of three positive chronic haemodialysis patients. Under strict preventive measures, only one patient out of 21 patient-contacts and 29 personnel-contacts tested positive within 2 weeks after the last contact. This patient, case #3, most likely became infected during unprotected, organised group transportation to the dialysis centre.

This study determined farm management factors associated with long-duration bovine tuberculosis (bTB) breakdowns disclosed in the period 23 May 2016 to 21 May 2018; a study area not previously subject to investigation in Northern Ireland. A farm-level epidemiological investigation (n = 2935) was completed when one or more Single Intradermal Comparative Cervical Test (SICCT) reactors or when one or more confirmed (positive histological and/or bacteriological result) lesion at routine slaughter were disclosed. A case-control study design was used to construct an explanatory set of management factors associated with long-duration bTB herd breakdowns; with a case (n = 191) defined as an investigation into a breakdown of 365 days or longer. Purchase of infected animal(s) had the strongest association as the most likely source of infection for long-duration bTB herd breakdowns followed by badgers and then cattle-to-cattle contiguous herd spread. However, 73.5% (95% CI 61.1–85.9%) of the herd type contributing to the purchase of infection source were defined as beef fattening herds. This result demonstrates two subpopulations of prolonged bTB breakdowns, the first being beef fattening herds with main source continuous purchase of infected animals and a second group of primary production herds (dairy, beef cows and mixed) with risk from multiple sources.

We used social network analysis (SNA) to study the novel coronavirus (COVID-19) outbreak in Karnataka, India, and to assess the potential of SNA as a tool for outbreak monitoring and control. We analysed contact tracing data of 1147 COVID-19 positive cases (mean age 34.91 years, 61.99% aged 11–40, 742 males), anonymised and made public by the Karnataka government. Software tools, Cytoscape and Gephi, were used to create SNA graphics and determine network attributes of nodes (cases) and edges (directed links from source to target patients). Outdegree was 1–47 for 199 (17.35%) nodes, and betweenness, 0.5–87 for 89 (7.76%) nodes. Men had higher mean outdegree and women, higher mean betweenness. Delhi was the exogenous source of 17.44% cases. Bangalore city had the highest caseload in the state (229, 20%), but comparatively low cluster formation. Thirty-four (2.96%) ‘super-spreaders’ (outdegree ⩾ 5) caused 60% of the transmissions. Real-time social network visualisation can allow healthcare administrators to flag evolving hotspots and pinpoint key actors in transmission. Prioritising these areas and individuals for rigorous containment could help minimise resource outlay and potentially achieve a significant reduction in COVID-19 transmission.

In order to understand queueing performance given only partial information about the model, we propose determining intervals of likely values of performance measures given that limited information. We illustrate this approach for the mean steady-state waiting time in the $GI/GI/K$ queue. We start by specifying the first two moments of the interarrival-time and service-time distributions, and then consider additional information about these underlying distributions, in particular, a third moment and a Laplace transform value. As a theoretical basis, we apply extremal models yielding tight upper and lower bounds on the asymptotic decay rate of the steady-state waiting-time tail probability. We illustrate by constructing the theoretically justified intervals of values for the decay rate and the associated heuristically determined interval of values for the mean waiting times. Without extra information, the extremal models involve two-point distributions, which yield a wide range for the mean. Adding constraints on the third moment and a transform value produces three-point extremal distributions, which significantly reduce the range, producing practical levels of accuracy.