Environmental exposures are known to be associated with pathogen transmission and immune impairment, but the association of exposures with aetiology and severity of community-acquired pneumonia (CAP) are unclear. A retrospective observational study was conducted at nine hospitals in eight provinces in China from 2014 to 2019. CAP patients were recruited according to inclusion criteria, and respiratory samples were screened for 33 respiratory pathogens using molecular test methods. Sociodemographic, environmental and clinical factors were used to analyze the association with pathogen detection and disease severity by logistic regression models combined with distributed lag nonlinear models. A total of 3323 CAP patients were included, with 709 (21.3%) having severe illness. 2064 (62.1%) patients were positive for at least one pathogen. More severe patients were found in positive group. After adjusting for confounders, particulate matter (PM) 2.5 and 8-h ozone (O3-8h) were significant association at specific lag periods with detection of influenza viruses and Klebsiella pneumoniae respectively. PM10 and carbon monoxide (CO) showed cumulative effect with severe CAP. Pollutants exposures, especially PM, O3-8h, and CO should be considered in pathogen detection and severity of CAP to improve the clinical aetiological and disease severity diagnosis.

Ulcerative colitis (UC) is a chronic inflammatory disease involving the colon and rectum. One of the most modifiable environmental factors affecting UC severity is the patient’s dietary pattern. Although the role of dietary patterns on UC aetiology has been investigated previously, its relationship with disease severity has not yet been elucidated. This study examined the association between UC patients’ dietary patterns and disease severity. This cross-sectional study was conducted in 340 UC patients. Using an FFQ, food patterns were assessed. Twenty-five food categories were categorised based on the similarity of the nutrient composition of the food using the factor analysis method. A simple clinical colitis activity index was used to determine disease severity. Three dietary patterns were identified based on the factor analysis: healthy, unhealthy and Western dietary pattern. After adjusting for potential confounding factors, patients who were in the highest tertile of healthy dietary pattern compared with the lowest tertile were 92 % less likely to have severe UC (OR: 0·08; 95 % CI: 0·03, 0·22). Also, those in the highest tertile of the Western dietary pattern were 3·86 times more likely to have severe UC than those in the lowest tertile (OR: 3·86; 95 % CI: 1·86, 8·00). Even after controlling for confounding variables, unhealthy dietary pattern did not increase the risk of severe UC. Our data indicate the beneficial role of healthy dietary pattern in amelioration of disease severity in UC patients. To confirm this association, more studies are needed, especially prospective cohort studies.

The SARS-CoV-2 Omicron variant has increased infectivity and immune escape compared with previous variants, and caused the surge of massive COVID-19 waves globally. Despite a vast majority (~90%) of the population of Santa Fe city, Argentina had been vaccinated and/or had been infected by SARS-CoV-2 when Omicron emerged, the epidemic wave that followed its arrival was by far the largest one experienced in the city. A serosurvey conducted prior to the arrival of Omicron allowed to assess the acquired humoral defences preceding the wave and to conduct a longitudinal study to provide individual-level real-world data linking antibody levels and protection against COVID-19 during the wave. A very large proportion of 1455 sampled individuals had immunological memory against COVID-19 at the arrival of Omicron (almost 90%), and about half (48.9%) had high anti-spike immunoglobulin G levels (>200 UI/ml). However, the antibody titres varied greatly among the participants, and such variability depended mainly on the vaccine platform received, on having had COVID-19 previously and on the number of days elapsed since last antigen exposure (vaccine shot or natural infection). A follow-up of 514 participants provided real-world evidence of antibody-mediated protection against COVID-19 during a period of high risk of exposure to an immune-escaping highly transmissible variant. Pre-wave antibody titres were strongly negatively associated with COVID-19 incidence and severity of symptoms during the wave. Also, receiving a vaccine shot during the follow-up period reduced the COVID-19 risk drastically (15-fold). These results highlight the importance of maintaining high defences through vaccination at times of high risk of exposure to immune-escaping variants.

To explore whether higher degrees of electrophysiological abnormalities are associated with a more frequent exposure to a more aggressive treatment regimen, we performed a retrospective chart review of patients attending the neuromuscular clinic from June 2012 to December 2015 and included 87 patients. We compared treatment regimens during the follow-up period between patients with high and low jitter and decrement. Myasthenia gravis patients with high jitter or decrement at baseline were more frequently treated with intravenous immunoglobulins (IVIG) and/or plasma exchange (PLEX) during the follow-up period. In patients with mild disease, IVIG or PLEX treatment was associated with high decrement.

Wild relative of okra, Abelmoschus angulosus Wall. ex Wight & Arn. was identified as a resistant germplasm for Okra Yellow Vein Mosaic Virus (OYVMV) which is the devastating disease for okra cultivation in Sri Lanka. The mode of resistance of OYVMV in A. angulosus was studied with the aim of tagging responsible genes for the disease resistance. Wide hybridization was performed between A. angulosus and highly virus susceptible A. esculentus variety, MI-7. Very poor seed setting was observed in F1 and F2 generations due to post zygotic abortion. Disease screening was carried out using F1 and F2:3 populations along with parents in the field under induced disease pressure. Disease severity index and area under disease progress curve were calculated to measure disease severity. Number of genes segregating for OYVMV disease resistance was calculated for the F2:3 generation. Modified Wright's formula was used to estimate the effective gene number and mode of inheritance by a quantitative method. A χ2 test was performed for qualitative analysis. Plants of A. angulosus were totally free of virus incidence while 100% disease incidence was observed in the variety MI-7. F2:3 population showed between and within progeny segregation for disease incidence. Results indicated that the disease susceptibility was dominant over resistance. χ2 analysis revealed that the segregation of disease severity was significantly fit to the gene model of 9:6:1 (χ2 = 0.1757 at P ≤ 0.05) suggesting the disease resistance in A. angulosus is governing by two recessive genes in an additive manner. Result was confirmed by the quantitative analysis.

Previous greenhouse studies with a noncommercial glyphosate-resistant sugarbeet variety indicated that susceptibility to Rhizoctonia crown and root rot could increase after glyphosate was applied. Greenhouse and field experiments were conducted in 2008 and 2009 to determine if glyphosate influenced disease severity in potential commercially available varieties of glyphosate-resistant sugarbeet. In the first greenhouse experiment in 2008, Hilleshög 9027RR, the most tolerant variety to Rhizoctonia crown and root rot, exhibited an increase in disease severity when glyphosate was applied. There were no significant differences between herbicide treatments in Hilleshög 9028RR, and glyphosate decreased disease severity in Hilleshög 9032RR when compared with the no-herbicide treatment. Experiments conducted to determine if glyphosate influenced Rhizoctonia solani growth in vitro indicated that glyphosate did not increase the radial growth of R. solani, except at 10× (190 µg ae ml−1) the normal rate of glyphosate plus ammonium sulfate (AMS). Field and additional greenhouse experiments were conducted using four commercial varieties. Differences in disease severity were observed when comparing varieties, but glyphosate did not significantly influence the severity of Rhizoctonia crown and root rot when compared with the no-herbicide control. Choosing a glyphosate-resistant sugarbeet variety with the best demonstrated tolerance to Rhizoctonia crown and root rot is an important factor in reducing disease severity and maintaining sugarbeet yield.

A novel influenza virus emerged in the United States in spring 2009, rapidly becoming a global pandemic. Children were disproportionally affected by the novel influenza A(H1N1) pandemic virus [A(H1N1)pdm]. This retrospective electronic medical record review study aimed to identify clinical predictors of disease severity of influenza A(HIN1)pdm infection in paediatric patients. Disease severity was defined on an increasing three-level scale from non-hospitalized, hospitalized, and admitted to the intensive care unit (ICU). From April 2009 to June 2010, 696 children presented to Texas Children's Hospital's emergency department, 38% were hospitalized, and 17% were admitted to the ICU. Presenting symptoms associated with severe influenza were dyspnoea [odds ratio (OR) 5·82], tachycardia (OR 2·61) and fatigue (OR 1·96). Pre-existing health conditions associated with disease severity included seizure disorder (OR 4·71), obesity (OR 3·28), lung disease (OR 2·84), premature birth (OR 2·53), haematological disease (OR 2·22), and developmental delay (OR 2·20). According to model fitness tests, presenting symptoms were more likely to predict severe influenza than underlying medical conditions. However, both are important risk factors. Recognition of clinical characteristics associated with severe disease can be used for triaging case management of children during future influenza outbreaks.

Objectives: The aim of this study was to get insight in what criteria as presented in Health technology assessment (HTA) studies are important for decision makers in healthcare priority setting.

Methods: We performed a discrete choice experiment among Dutch healthcare professionals (policy makers, HTA experts, advanced HTA students). In twenty-seven choice sets, we asked respondents to elect reimbursement of one of two different healthcare interventions, which represented unlabeled, curative treatments. Both treatments were incrementally compared with usual care. The results of the interventions were normal outputs of HTA studies with a societal perspective. Results were analyzed using a multinomial logistic regression model. Upon completion of the questionnaire, we discussed the exercise with policy makers.

Results: Severity of disease, costs per quality-adjusted life-year gained, individual health gain, and the budget impact were the most decisive decision criteria. A program targeting more severe diseases increased the probability of reimbursement dramatically. Uncertainty related to cost-effectiveness was also important. Respondents preferred health gains that include quality of life improvements over extension of life without improved quality of life. Savings in productivity costs were not crucial in decision making, although these are to be included in Dutch reimbursement dossiers for new drugs. Regarding subgroups, we found that policy makers attached relatively more weight to disease severity than others but less to uncertainty.

Conclusions: Dutch policy makers and other healthcare professionals seem to have reasonably well articulated preferences: six of seven attributes were significant. Disease severity, budget impact, and cost-effectiveness were very important. The results are comparable to international studies, but reveal a larger set of important decision criteria.

Host–parasite interactions were studied for the microsporidium Pleistophora intestinalis and its host, Daphnia magna. Two host clones were established from the same population from which the parasites were taken (home-1 and 2), and two clones from two other ponds (neighbour and Munich clone). With increasing clutch number infected females from home-1 clone produced relatively smaller clutches than uninfected females. Age and body length at maturity were not affected by the infection, but body length of the sixth adult instar was reduced. In an experiment including all four host clones, the parasite reproduced well in the two home clones and in the neighbour clone, but poorly in the Munich clone. Juvenile growth and age at maturity was not affected in the two home clones, but for the neighbour and the Munich clone age was delayed by 2·2 days and 4·1 days, and juvenile growth reduced by 16 and 23%, respectively. Significant host-clone x parasite-treatment interactions were also found for size at maturity and clutch size. This pattern of host-parasite interactions suggests that there is no general positive relation between disease severity and parasite multiplication rate.

The size of the infecting inoculum may influence the severity of malaria, but evidence is scarce. Malaria therapy records provide a unique source of information on induced malaria in people. The therapy was given to large numbers of neurosyphilis patients and the malaria was left untreated as long as possible. Data from patients treated at the Horton Hospital, Epsom 1923–60 with a single strain of vivax malaria were analysed to assess the influence of inoculum size on severity of disease. Malaria was induced by mosquito bite, blood inoculation or direct sporozoite inoculation. The different measures of inoculum size were inversely correlated with pre-patent period, as expected. Overall, information was available on a total of 563 non-immune patients who were not treated during the first 5 days of patent parasitaemia. No strong or consistent relationships were found between measures of inoculum size and any of the measures of severity used: neither parasitaemia levels, nor peak fevers, nor number of paroxysms of fever. In the largest data set, longer pre-patent periods were associated with tertian fever, spontaneous recovery and less use of modifying treatment. Difficulties in interpreting the results are discussed, particularly with respect to misclassification of both exposure and outcome variables. While an inoculum size-severity relationship cannot be ruled out, a strong relationship is very unlikely.

The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α) is associated with malaria virulence (disease severity) in both rodents and humans. We are interested in whether parasite genetic diversity influences TNF-mediated effects on malaria virulence. Here, primary infections with genetically distinct Plasmodium chabaudi chabaudi (P.c.c.) clones varied in the virulence and cytokine responses induced in female C57BL/6 mice. Even when parasitaemia was controlled for, a greater day 7 TNF-α response was induced by infection with more virulent P.c.c. clones. Since many functions of TNF-α are exerted through TNF receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR-1 blockade ameliorated the weight loss but not the anaemia induced by malaria infection, regardless of P.c.c. clone. We show that distinct P.c.c. infections induced significantly different plasma interferon gamma (IFN-γ), interleukin 6 (IL-6) and interleukin 10 (IL-10) levels. Our results demonstrate that regardless of P.c.c. genotype, blocking TNFR1 signalling protected against weight loss, but had negligible effects on both anaemia and asexual parasite kinetics. Thus, during P.c.c. infection, TNF-α is a key mediator of weight loss, independent of parasite load and across parasite genotypes.

Recrudescing Plasmodium falciparum parasitaemia is attributed to the switching of PfEMP1, a variant antigen family encoded by the var gene repertoire, and the host's immune response. We have developed a mathematical model which incorporates var gene switching, and variant specific, non-variant specific and non-specific immunity. By conducting a sensitivity analysis of the model we have defined the parameter limits which produce chronic and recrudescing infections. We explore 3 switching mechanisms: ordered, random and uncoupled switching. We show that if var genes switch on and off independently at variable rates through the repertoire a chronic clinical infection is predicted. The fastest switching-on rate that produces a chronic infection is 0·03% per generation. The model predicts that non-variant specific immunity plays an important role in reducing disease severity. This work illustrates the complex relationship between the malaria parasite and its host and shows that var gene switching at rates substantially slower than 2% are essential for parasite survival.

Experiments were designed to look at the relationship between infective dose and disease severity using 2 clones of Plasmodium chabaudi that differ in virulence. We asked whether there were dose–severity relationships, whether clone differences in virulence were maintained over a range of doses, and whether disease severity could be accounted for by parasite dynamics. Groups of mice were infected with parasite doses differing by an order of magnitude, ranging from 100 to 1×108 parasites. Infective dose affected the probability of death, but only with the more virulent clone. Dose also affected morbidity. For both clones, higher doses induced greater anaemia. Larger doses caused greater weight loss, but only for infections with the more virulent clone. Here, for a given dose, mice lost a fixed amount of weight, irrespective of their initial weight. Larger doses induced earlier mortality and morbidity than did lower dose treatments. Finally, dose affected parasite dynamics, with earlier and higher peak parasite densities in larger dose infections. All these effects were small relative to clone differences in disease severity, which were apparent across the range of doses. Dose effects were manifested through the timing and/or magnitude of peak parasite densities, broadly supporting the idea that dose affects disease severity by altering the time the host has to control parasite densities and ameliorate the effects of parasites. We discuss the possible efficacy of intervention strategies aimed at reducing human disease severity by reducing infective parasite dose.