- Volume 2, Issue 9, 2020
Volume 2, Issue 9, 2020
- Personal View
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Lessons from studies with murine cytomegalovirus that could lead to a safe live attenuated vaccine for human cytomegalovirus
More LessStudies with a murine cytomegalovirus mutant tsm5 suggested two possible approaches to producing a live attenuated human cytomegalovirus vaccine. One approach would be to use a combination of five to six mutants where an attenuating mutation in the gene of one mutant is compensated by the wild-type version in a second mutant, which in turn has a mutation in a different gene compensated by the wild-type version in a third mutant, etc. Important genes in this approach could include those involved in DNA replication. The importance of the carboxy terminase of the primase gene (M70/UL70) for its function suggested a second approach where some of the natural codons in this region could be substituted with synonymous non-preferred (minor) codons that would reduce the replication fitness of the mutant.
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- Research Article
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Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease
Introduction. Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro.
Methods. In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient’s isolate and comparison clinical isolates and quantified by Hill’s slopes calculated from time–kill curves.
Results. M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient’s isolate was found to be the least susceptible strain in vitro.
Conclusion. These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.
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Epidemiological profile of Neisseria meningitidis in Casablanca, Morocco: 2010–2019
Surveillance of invasive meningococcal diseases (IMD) must be carried out regularly and continuously in order to detect the emergence of strains of reduced susceptibility to antibiotics for therapeutic and prophylactic use and the appearance of new invasive clones. Molecular-typing approaches allow reliable traceability and powerful epidemiological analysis. This is an epidemiological study of Neisseria meningitidis causing meningitis in Casablanca, Morocco. The grouping was confirmed by PCR mainly on the isolates from cerebrospinal fluid (CSF). A total of 245 confirmed isolates of N .meningitidis were obtained between 2010 and 2019 of which 93 % are of group B. Overall, 24 % of all the isolates have a reduced susceptibility to penicillin G, but no resistance to penicillin G has been reported. All the isolated strains are susceptible to third-generation cephalosporins (3GCs). Genotyping by multilocus sequence typing (MLST) of a selection of 18 strains showed that the majority of isolates belong to the invasive clonal complex CC 32(9/18) followed by the CC 41/44(3/18).
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- Method
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Easy phylotyping of Escherichia coli via the EzClermont web app and command-line tool
More LessThe Clermont PCR method for phylotyping Escherichia coli remains a useful classification scheme even though genome sequencing is now routine, and higher-resolution sequence typing schemes are now available. Relating present-day whole-genome E. coli classifications to legacy phylotyping is essential for harmonizing the historical literature and understanding of this important organism. Therefore, we present EzClermont – a novel in silico Clermont PCR phylotyping tool to enable ready application of this phylotyping scheme to whole-genome assemblies. We evaluate this tool against phylogenomic classifications, and an alternative software implementation of Clermont typing. EzClermont is available as a web app at www.ezclermont.org, and as a command-line tool at https://nickp60.github.io/EzClermont/.
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- Short Communication
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Experimental inoculation of CD11c+ B1 lymphocytes, CD68+ macrophages, or platelet-rich plasma from scrapie-infected sheep into susceptible sheep results in variable infectivity
More LessMany studies have demonstrated prion infectivity in whole blood and blood components in a variety of transmissible spongiform encephalopathies of livestock and rodents, and variant Creutzfeldt–Jakob disease in humans, as well as an association between pathogenic prion protein (PrPSc) and different immune cells (e.g. follicular dendritic cells, T and B lymphocytes, monocytes and tingible body macrophages). To further investigate the role of various blood components in prion disease transmission, we intracranially inoculated genetically susceptible VRQ/ARQ and ARQ/ARQ sheep with inocula composed of CD11c+ B1 lymphocytes, CD68 +macrophages, or platelet-rich plasma derived from clinically ill sheep infected with the US no. 13–7 scrapie agent. At the completion of the study, we found that VRQ/ARQ and ARQ/ARQ sheep inoculated with CD11c+ B1 lymphocytes and CD68+ macrophages developed scrapie with detectable levels of PrPSc in the central nervous system and lymphoreticular system, while those inoculated with platelet-rich plasma did not develop disease and did not have detectable PrPSc by immunohistochemistry or enzyme immunoassay. This study complements and expands on earlier findings that white blood cells harbour prion infectivity, and reports CD11c+ B1 lymphocytes and CD68+ macrophages as additional targets for possible preclinical detection of prion infection in blood.
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- Case Report
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An unusual case of Scedosporium apiospermum fungaemia in an immunocompetent patient with a left ventricular assist device and an implantable cardiac device
More LessLeft ventricular assist device (LVAD)-related infections are a leading cause of morbidity and mortality, with fungal infections being particularly difficult to manage. We report a case of an immunocompetent 39-year-old male with an LVAD and an implantable cardiac device (ICD) who developed fatal Scedosporium apiospermum fungaemia. To the best of our knowledge, this is the first reported case of LVAD-related S. apiospermum fungaemia.
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Pleural empyema due to Salmonella in a patient with bronchogenic carcinoma: the first case report from a cancer hospital in Egypt
More LessBackground. Salmonella species are motile, Gram-negative facultative anaerobic bacilli, which belong to the family Enterobacteriaceae . The most common clinical presentations of Salmonella infection are gastroenteritis and enteric fever. Detection of Salmonella organisms in empyema is very rare.
Case presentation. We report the case of a 66-year-old female patient with bronchogenic carcinoma who developed empyema, and Salmonella was identified from the culture of pleural fluid. After antimicrobial therapy and other therapeutic measures, including the insertion of an intercostal tube, oxygen supplementation, frequent suction of respiratory secretions, and chest physiotherapy, the patient's condition improved. To the best of our knowledge, this is the first case to be reported in Egypt.
Conclusions. Our case sheds light on the role of Salmonella in immunocompromised patients in general and cancer patients in specific. We recommend further study of this role, since it may lead to a better understanding of the pathogenicity of this organism in these patients.
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An unusual presentation of cutaneous histoplasmosis as a recurrent solitary and spontaneously healing lesion in an immunocompetent patient
Infection with Histoplasma capsulatum typically manifests as a self-limiting pulmonary disease in immunocompetent patients. Systemic symptoms such as cutaneous lesions are associated with immunodeficient states. Our patient was an immunocompetent 68-year-old male who presented with a plaque on his left infraorbital area that was concerning for malignancy. Histological examination of the lesion revealed granulomatous inflammation and small yeast forms suggestive of H. capsulatum. The lesion resolved spontaneously and recurred 1 year later. On recurrence, histological examination again revealed yeast forms consistent with H. capsulatum. Serum and urine testing for H. capsulatum antigen were negative. Next-generation sequencing detected H. capsulatum, which supported the diagnosis of a cutaneous infection. The patient was prescribed and started treatment with itraconazole for 1 year after recurrence of the lesion, and he has not reported further disease recurrence to date. This case is unique because of the presentation of a primary cutaneous recurrent H. capsulatum lesion, and it demonstrated the utility of laboratory testing in its diagnosis.
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Prevalence and resistance pattern of uropathogens from community settings of different regions: an experience from India
Sarita Mohapatra, Rajashree Panigrahy, Vibhor Tak, Shwetha J. V., Sneha K. C., Susmita Chaudhuri, Swati Pundir, Deepak Kocher, Hitender Gautam, Seema Sood, Bimal Kumar Das, Arti Kapil, Pankaj Hari, Arvind Kumar, Rajesh Kumari, Mani Kalaivani, Ambica R., Harshal Ramesh Salve, Sumit Malhotra and Shashi Kant
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