[Risk factors for the development of airway hyperresponsiveness in patients with allergic rhinitis].

Allergic rhinitis（AR） is an independent risk factor for allergic asthma. Some AR patients may have developed airway hyperresponsiveness（AHR） in the absence of asthma symptoms. In this stage, AHR is often neglected due to the absence of typical asthma symptoms. Exploring the clinically relevant risk factors for AHR in patients with AR, as well as the clinical indicators and biomarkers to predict AHR in patients with AR, is of great significance to the prevention of the occurrence of AHR and asthma. This review summarized the risk factors for the development of AHR in AR patients, and gave hints to the prevention of AHR in AR patients.

Serological surveillance on potential Plasmodium vivax exposure risk in a post-elimination setting.

China was declared malaria free in June of 2021. In the post-elimination setting, vigilant surveillance is essential to sustain malaria free status. Serological surveillance has been recognized as an efficient tool for assessing the immunity levels and exposure risk in a population. In this study, a cross-sectional serological survey was conducted in Yingjiang County, China, in August-September, 2021. The study sites were villages along the borders with Myanmar, which have no local transmission since the last indigenous case registered in 2016. A total of 923 participants from six villages were enrolled. The majority was aged > 36 years (56.12%) and 12.46% (115/923) participants had experienced malaria infection at least once. A magnetic- bead-based assay was used to test antibodies against Plasmodium vivax antigen PvMSP-119 to evaluate the prevalence of antibody positive subjects. A reversible catalytic model was used to assess the risk of exposure. The prevalence of anti-PvMSP-119 IgG was 12.84% [95% confidence interval (CI): 9.22%-16.47%], 13.93% (95% CI: 10.11%-17.74%), and 3.57% (95% CI: 1.40%-5.75%) in three different line-of-defense areas, which differed significantly (P < 0.0001). The prevalence of anti-PvMSP-119 IgG increased with age and no statistically significant difference was detected between the sexes. The reversible catalytic model indicated that the seropositive conversion rate and seronegative reversion rate were 0.0042, 0.0034, 0.0032 and 0.0024, 0.0004, 0.0065 in the first-, second-line-of-defense area and total areas, respectively, and the fitted value did not differ significantly from the observed value (P > 0.1). Although this study found the prevalence of antibody-positive subjects and the seroconversion rate in this post-elimination setting were lower than that in transmission setting, the population still had an exposure risk. Serological surveillance should be considered in post-elimination settings to provide valuable information with which to evaluate the risk of malaria re-establishment.

Effect of Haemophilus influenzae, Streptococcus pneumoniae and influenza vaccinations on infections, immune response and asthma control in preschool children with asthma.

BACKGROUND: Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (pneumococcus) and influenza vaccines are administered in children to prevent infections caused by these pathogens. The benefits of vaccination for asthma control in children and the elicited immune response are not fully understood. This study aimed to investigate the impact of these vaccinations on respiratory infections, asthma symptoms, asthma severity and control status, pathogen colonization and in vitro immune responses to different stimulants mimicking infections in asthmatic children. METHODS: Children aged 4-6 years were recruited into the multicentre prospective PreDicta study conducted across five European countries. Information about vaccination history, infections, antibiotic use, inhaled corticosteroid (ICS) use and asthma symptoms in the last 12 months were obtained from questionnaires of the study. Nasopharyngeal samples were collected at the first visit to assess bacterial and viral colonization, and venous blood for isolation of peripheral blood mononuclear cells (PBMCs). The PBMCs were stimulated with phytohemagglutinin, R848, Poly I:C and zymosan. The levels of 22 cytokines and chemokines were measured in cell culture supernatants using a luminometric multiplex assay. RESULTS: One-hundred and forty asthmatic preschool children (5.3 ± 0.7 years) and 53 healthy children (5.0 ± 0.8 years) from the PreDicta cohort were included in the current study. Asthmatic children were associated with more frequent upper and lower respiratory infections, and more frequent and longer duration of antibiotic use compared with healthy children. In asthmatic children, sufficient H. influenzae vaccination was associated with a shorter duration of upper respiratory infection (URI) and overall use and average dose of ICS. The airway colonization was characterized by less pneumococcus and more rhinovirus. Pneumococcal vaccination was associated with a reduction in the use rate and average dose of ICS, improved asthma control, and less human enterovirus and more H. influenzae and rhinovirus (RV) airway colonization. Influenza vaccination in the last 12 months was associated with a longer duration of URI, but with a decrease in the occurrence of lower respiratory infection (LRI) and the duration of gastrointestinal (GI) infection and antibiotic use. Asthmatic preschoolers vaccinated with H. influenzae, pneumococcus or influenza presented higher levels of Th1-, Th2-, Th17- and regulatory T cells (Treg)-related cytokines in unstimulated PBMCs. Under stimulation, PBMCs from asthmatic preschoolers with pneumococcal vaccination displayed a predominant anti-inflammatory immune response, whereas PBMCs from asthmatic children with sufficient H. influenzae or influenza vaccination were associated with both pro- and anti-inflammatory immune responses. CONCLUSION: In asthmatic preschoolers, the standard childhood vaccinations to common respiratory pathogens have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis.

Prevalence of antifolate drug resistance markers in Plasmodium vivax in China.

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar.

BACKGROUND: Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanmar was aimed at estimating the underlying drug resistance in this region. METHODS: Blood samples from patients with vivax malaria were collected from Laiza city in northeastern Myanmar in 2020. Drug resistance genes including Pvcrt-o, Pvmdr1, Pvdhfr and Pvdhps were amplified and sequenced. Genetic polymorphisms and haplotypes were analysed to evaluate the prevalence of mutant alleles associated with drug resistance. RESULTS: A total of 149 blood samples from P. vivax patients were collected. The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100.0% and 52.0%, respectively, whereas no single nucleotide polymorphism was present at codon 976. The proportions of single and double mutant types were 48.0% and 52.0%, respectively. A K10 "AAG" insertion in the Pvcrt-o gene was not detected. Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 29.9%, 54.3%, 27.6%, 44.9% and 55.1% of the samples, respectively. Wild type was predominant (46.3%), followed by quadruple and double mutant haplotypes. Of three types of tandem repeat variations of Pvdhfr, Type B, with three copies of GGDN repeats, was the most common. Pvdhps mutations were only detected at codons 383 and 553 and the wild type Pvdhps was dominant (78.0%). Eleven haplotypes were identified when combining the mutations of Pvdhfr and Pvdhps, among which the predominant one was the wild type (33.9%), followed by double mutant alleles S58R/S117N /WT (24.6%). CONCLUSIONS: This study demonstrated resistant P. vivax phenotypes exists in northeastern Myanmar. Continued surveillance of drug resistance markers is needed to update treatment guidelines in this region.

Inorganic Pillar Center-Facilitated Counterdiffusion Synthesis for Highly H2 Perm-Selective KAUST-7 Membranes.

Fluorinated metal-organic framework materials (NbOFFIVE-1-Ni, also referred to as KAUST-7) have attracted widespread attention because of their high chemical stability and thermal stability, outstanding tolerance with water and H2S, and high CO2-adsorption selectivity over H2 and CH4. KAUST-7 was expected to be a new membrane material candidate for H2/CO2 separation because of the hindered permeation of CO2 resulting from the interaction between CO2 and (NbOF5)2- of the KAUST-7 framework. A highly H2 perm-selective KAUST-7 membrane was first achieved using a novel strategy of inorganic pillar center-facilitated counterdiffusion (IPCFCD) proposed by us. The IPCFCD method not only effectively avoided the corrosion of hydrofluoric acid to α-Al2O3 tubes in the process of preparing KAUST-7 membranes, but also better reduced grain boundary defects because of the faster nucleation rate and resultant high crystallinity. The KAUST-7 membrane exhibited a high H2/CO2 separation factor (SF) of 27.30 for the 1:1 H2/CO2 binary gas mixture with a high H2 permeance of 5.30 × 10-7 mol m-2 s-1 Pa-1 under ambient conditions and a slight decrease of the H2/CO2 SF with increasing operation temperature and presence of steam. This study highlighted the importance of pre-synthesizing inorganic pillar centers (NiNbOF5 intermediate) and the innovation of a membrane formation process for synthesizing polycrystalline KAUST-7 membranes. Most important of all, our study provided a novel approach to overcome the challenge in fabricating metal-organic framework membranes containing corrosive reactants for the corresponding supports.

Epidemiologic Analysis of Efforts to Achieve and Sustain Malaria Elimination along the China-Myanmar Border.

Malaria cases have dramatically declined in China along the Myanmar border, attributed mainly to adoption of the 1-3-7 surveillance and response approach. No indigenous cases have been reported in China since 2017. Counties in the middle and southern part of the border area have a higher risk for malaria importation and reestablishment after elimination.

Epidemiological characterization of imported recurrent Plasmodium vivax and Plasmodium ovale in China, 2013-2020.

BACKGROUND: China has reached important milestones in the elimination of malaria. However, the numbers of imported recurrent cases of Plasmodium vivax and P. ovale are gradually increasing, which increases the risk of malaria re-establishment in locations where Anopheles mosquitoes exist. The aim of this study is to characterize the epidemiological profiles of imported recurrent P. vivax and P. ovale cases, quantifying the recurrence burden and guiding the development of appropriate public health intervention strategies. METHODS: Individual-level data of imported recurrent P. vivax and P. ovale cases were collected from 2013 to 2020 in China via the Parasitic Diseases Information Reporting Management System. Demographic characteristics, temporal and spatial distributions, and the interval from previous infection to recurrence were analyzed by SAS, ArcGIS and GraphPad Prism software, respectively, to explore the epidemiological profiles of imported recurrent cases. RESULTS: A total of 307 imported recurrent cases, including 179 P. vivax and 128 P. ovale cases, were recorded. The majority of cases occurred in males (P. vivax 91.1%, P. ovale 93.8%) and migrant workers (P. vivax 43.2%, P. ovale 44.7%). Individuals aged 30-39 years had the highest P. vivax and P. ovale recurrent infection rates, respectively. The number of imported recurrent cases of infection by these two malaria species increased from 2013 to 2018, and P. vivax infection showed well-defined seasonality, with two peaks in February and June, respectively. More than 90% of patients with recurrent cases did not receive radical treatment for previous infection. Most imported recurrent P. vivax cases were reported in Yunnan Province and were imported from Myanmar, Ethiopia, and Pakistan, while most recurrent P. ovale cases were reported in southern China and primarily imported from Cameroon, Ghana, and Nigeria. The intervals from previous malaria infection to recurrence among different continents were significantly different (P = 0.0016) for P. vivax malaria but not for P. ovale malaria (P = 0.2373). CONCLUSIONS: The large number of imported recurrent cases has been a major challenge in the prevention of malaria re-establishment in China. This study provides evidence to guide the development of appropriate public health intervention strategies for imported recurrent P. vivax and P. ovale cases.

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China.

BACKGROUND: The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. METHODS: Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. RESULTS: A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. CONCLUSION: This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.