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Canadian Journal of Infectious Diseases and Medical Microbiology publishes original research articles, review articles, and clinical studies related to infectious diseases of bacterial, viral and parasitic origin.
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Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children
Recent evidence suggests that proprotein convertase subtilisin/kexin type 9 (PCSK9), a downmodulator of cellular uptake of blood cholesterol, also negatively impacts host immune response to microbial infection. In this study, we investigated whether carrying the loss-of-function (LOF) rs562556 (c.1420 A > G; p.I474 V) PCSK9 single nucleotide polymorphism (SNP) affected the outcome of severe malaria in children. Archival DNA of a cohort of 207 Malian children suffering from severe malaria was genotyped for the rs562556 SNP. Sixty-four children were either heterozygous or homozygous for the minor G allele (carriers); 143 children were homozygous for the common A allele (noncarriers). Among carriers, there was one mortality case (1.6%), compared to 15 cases (10.5%) among noncarriers (), suggesting that the G allele is associated with better survival in severe malaria. Intriguingly, this allele did not negatively segregate with any of the clinical symptoms linked to mortality in this cohort. Studies are needed to determine whether PCSK9 inactivation promotes a protective immune response to malaria infection.
MiR-155-Mediated Deregulation of GPER1 Plays an Important Role in the Gender Differences Related to Inflammatory Bowel Disease
Aim. The incidence and clinical manifestations of inflammatory bowel disease (IBD) are thought to have gender differences, which suggests that the estrogen signaling pathway and intestinal flora may play key roles in the pathogenesis of IBD. In IBD, microRNA-155 (miR-155) is upregulated and regulates G protein coupled estrogen receptor (GPER1), which affects the intestinal flora. The objective of this study was to investigate the role of the estrogen receptors and miR-155 in the pathogenesis of IBD. Methods. From July 2018 to July 2019, in the Department of Gastroenterology at Daping Hospital, Army Military Medical University, a total of 50 patients with IBD were included in this study, and 24 healthy examinees were randomly selected as the control group. Colonoscopies were performed, and clinical characteristics and blood samples were collected from all of the subjects. The serum cytokine levels in the patients with IBD and the health donors were detected by ELISA, and the estrogen receptor level measurements for all of the participants were assessed by immunohistochemistry (IHC) and quantitative real-time PCR (qPCR). The miR-155 levels were detected by qPCR in all of the participants, and miR-155−/− mice were used to investigate the mechanism of miR-155 in the pathogenesis of IBD. Results. The clinical characteristics and medications were different for the IBD patients when gender was considered. The male patients produced more proinflammatory cytokines, and while GPER1 expression was downregulated, miR-155 was upregulated in the patients with IBD. MiR-155 showed proinflammatory activity, while GPER1 showed an anti-inflammatory response during the pathogenesis of IBD. The miR-155−/− mice showed improvements in weight loss, survival, rectal bleeding, colon length, and histopathological changes compared with the wild-type mice. Furthermore, the male miR-155−/− mice showed increased inflammation compared to the female miR-155−/− mice in the above aspects. Conclusion. This study presents evidence indicating that miR-155 plays a key role in the pathogenesis of IBD for the different genders. MiR-155 was upregulated and showed proinflammatory activity, whereas GPER1 showed an anti-inflammatory response during the pathogenesis of IBD. The results demonstrated that more proinflammatory cytokines and reduced GPER1 levels were observed in the male IBD patients. Thus, miR-155 was involved in the regulation of GPER1 and induced gender differences in IBD patients. MiR-155 may be a potential marker for IBD-targeted therapy.
A Retrospective Study on Amoxicillin Susceptibility in Severe Haemophilus influenzae Pneumonia
Introduction. Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. Methods. A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. Results. Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, , chronic obstructive pulmonary disease (43% vs. 30% ), HAP (18% vs. 7%, , ventilator-associated pneumonia (27% vs. 17%, , and longer duration of mechanical ventilation (8 days vs. 6 days, ) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, ). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, ). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. Conclusions. Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.
Development and Evaluation of an iiPCR Assay for Salmonella and Shigella Detection on a Field-Deployable PCR System
Background. Salmonella and Shigella are often associated with fecal-oral transmission and cause large-scale outbreaks in centralized catering units and, therefore, should be frequently and strictly monitored, especially among food handlers. However, no specific and sensitive on-site detection method is available until now. Methods. In this study, an insulated isothermal PCR assay for the detection of Salmonella and Shigella on a field-deployable PCR system was developed. Specificity, sensitivity, reproducibility, and clinical accuracy of the assay were characterized and evaluated. Results. The insulated isothermal PCR assay could be completed within 58 minutes with minimal pretreatment needed. The assay was specific and with good reproducibility. The limit of detection was 103 CFU/mL and 101 CFU/mL for Salmonella and Shigella, respectively, which was comparable to multiplex real-time PCR. Mock on-site clinical evaluation results showed that the analytical sensitivity and specificity of the insulated isothermal PCR assay were 100% and 96.6%, while the positive predictive value and negative predictive value were 94.1% and 100%, respectively. Conclusion. Based on our results, we believe that the assay developed herein could serve as an alternative method for preliminary screening and provide a valuable platform for the on-site detection of Salmonella and Shigella, especially in resource-limited and developing countries.
Opportunistic Cryptococcal Antigenemia in the HAART Era at HIV Epidemic Settings of Northwest Ethiopia
Background. Cryptococcus neoformans is a frequent opportunistic infection in patients with the acquired immunodeﬁciency syndrome. While the advent of ART reduces the occurrence of cryptococcal meningitis in HIV patients, cryptococcal disease remains a leading cause of morbidity and mortality in the developing world especially in sub-Saharan Africa which is the epicenter of HIV. This study aimed to assess the cryptococcal antigenemia, CD4+ Th cell counts, HIV RNA viral load, and clinical presentations among HIV-positive patients in Northwest Ethiopia. Method. A total of two hundred (200) HIV-positive patients were recruited for this study. Cryptococcus antigenemia prevalence in plasma samples of HIV‐positive patients was determined by using Antigen lateral ﬂow assay (CrAg‐LFA) also, and CD4+ Th cell counts and HIV‐RNA levels were quantified from blood specimen. Patients’ demographic data, clinical manifestation, and concurrent opportunistic infection were recorded. Result. The sex distributions of study participants were 105(52.5%) male and 94(47.5%) female with an age range of 15–65 (mean 39.42 ± 9) years. All patients had a CD4+ T-cell count <100 cells/µl with the median 54 cells/μl and median HIV-RNA viral load 2.16 × 105 RNA copies/ml (50–3.66 × 105 RNA copies/ml); the prevalence of cryptococcal antigenemia was found to be 4% in HIV-positive patients. More than half and two third of CrAg‐positive patients had a CD4 count <25 cells/μl and HIV viral load >10,000 copies/ml, respectively, as well; Tuberculosis, Candidiasis, and herpes zoster are the most often observed concurrent infections while cryptococcal antigenemia is significantly associated with oral candidiasis (). Conclusion. Although the advent of ART, early diagnosis of cryptococcosis, and application of antifungal interventions, HIV-induced cryptococcal antigenemia positivity in HIV infected individuals is still the countries’ big challenge. Thus, stringent follow-up and case management should be considered.
Coinfection of High-Risk Human Papillomavirus and Lower Genital Tract Pathogens in the Development of High-Grade Cervical Lesions
Purpose. This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. Methods. Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. Results. The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (); however, higher infection rates with MH were not observed (). PB, UU, and CT were associated with HR-HPV infection (). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (). However, this was not the case for the CT (). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (). Conclusion. PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions.