Antimicrobial susceptibility patterns of uropathogens isolated from pregnant women in KwaZulu-Natal Province: 2011 - 2016

Background. Urinary tract infection (UTI) is one of the most common infections during pregnancy, which can lead to significant maternal and perinatal morbidity and mortality if left untreated. Challenges when treating UTIs in pregnancy include fetal protection and resistance development of uropathogens. Currently, the Essential Medicines List recommends nitrofurantoin to treat cystitis and ceftriaxone to treat pyelonephritis in pregnant women.Objectives. To determine common pathogens causing UTI in pregnancy and their antibiotic susceptibility patterns.Methods. A retrospective analysis was performed of laboratory data for positive urine specimens from obstetric departments of 6 KwaZulu- Natal Province hospitals during 2011 - 2016. Identification and susceptibility testing were performed using the VITEK 2 system. Results were interpreted according to the breakpoints of the Clinical and Laboratory Standards Institute, USA.Results. From 5 971 positive urine specimens, the most common isolate was Escherichia coli (n=3 236; 54.2%), followed by Klebsiella pneumoniae (n=770; 12.9%). Group B streptococcus (GBS) (n=239; 4.0%) and Enterococcus faecalis (n=251; 4.2%) were the most common Gram-positive pathogens. E. coli displayed significant resistance to trimethoprim-sulfamethoxazole (65.1%), cephalothin (38.3%), cefuroxime (27.3%), ciprofloxacin (16.9%) and amoxicillin-clavulanic acid (17.1%). Resistance to ceftriaxone and nitrofurantoin remained low ‒ 9.1% and 7.7%, respectively. Among Gram-positive pathogens, GBS displayed 100% penicillin susceptibility and E. faecalis showed 92.9% susceptibility to ampicillin.Conclusions. E. coli is unsurprisingly the most common cause of UTI in pregnancy in KwaZulu-Natal. Susceptibility to ceftriaxone and nitrofurantoin remains good. Among Gram positives, GBS is prevalent and susceptible to penicillin, while E. faecalis is susceptible to ampicillin. As antimicrobial resistance evolves, routine surveillance is necessary to modify recommended empirical antibiotic use

Surveillance and comparison of antimicrobial susceptibility patterns of ESKAPE organisms isolated from patients with bacteraemia in South Africa, 2016 - 2017

Background. In South Africa (SA), the National Department of Health has developed an Antimicrobial Resistance National Strategy Framework document to manage antimicrobial resistance (AMR). One of the strategic objectives is to optimise surveillance and early detection of AMR. At the National Institute for Communicable Diseases (NICD), an analysis of selected organisms and antimicrobial agents from both the public and the private sectors was conducted.Objectives. The relevance of surveillance for AMR is increasingly recognised in the light of global action plans to combat resistance. In this report, we present an overview of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) organisms and Escherichia coli reported from public and private sector laboratories in SA for the period 2016 - 2017.Methods. Antimicrobial susceptibility testing (AST) profiles on selected ESKAPE organisms and E. coli isolated from blood cultures from the public and private sectors in 2016 and 2017 were analysed. AST data were extracted from a web-based electronic platform created by the NICD. Drug-bug combinations following the World Health Organization’s Global Antimicrobial Surveillance System guidelines were included in the analysis.Results. A total of 28 920 ESKAPE organisms and E. coli were reported in 2016 and 32 293 in 2017 across the two health sectors. Proportions of some organisms differed between the two health sectors, such as E. coli (19% in the public sector and 36% in the private sector), A. baumannii (14% public and 4% private), P. aeruginosa (7% public and 11% private) and S. aureus (27% public and 17% private). Susceptibility data indicated changing patterns in both sectors towards an increase in non-susceptibility to carbapenems in K. pneumoniae (p<0.01). However, we demonstrated an increase in susceptibility to cloxacillin in S. aureus (p<0.01) in both sectors.Conclusions. The key clinically important finding is the rapidly decreasing carbapenem susceptibility among Enterobacteriaceae reported in SA, irrespective of sector. In addition, the analysis provides information that could be used to monitor the effectiveness of interventions implemented at a national level under the guidance and direction of the national AMR framework.

Application of IgM-capture ELISA on Myanmar Dengue Patients\u27 Serum Samples Collected in 1994

Seventy serum samples from clinically diagnosed dengue patients admitted to the North Okkalapa General Hospital, Yangon, Union of Myanmar, in 1994, were used to obtain the confirmed virological diagnosis by IgM-capture ELISA using all four types of dengue antigens raised by cell culture method. Sixty-two out of 70 specimens (88.6%) showed positive IgM ELISA titer against one or more assay antigen. Single application of dengue 2 antigen could detect 59 out of 62 positive sera (95.1% of total positives), whereas three more samples could be detected by using other serotypic antigens (either single antigen or double antigens in combination). Ten samples showing positive by single dengue antigen but negative results by the rest could possibly be due to the primary infection which showed serotype specific immune response

Optimization of the Dengue-2 Antigen ELISA Titer for the Positive Case Detection of Dengue Virus Infection by IgM ELISA

We have determined the dengue-2 antigen ELISA titer for the positive case detection of dengue virus infection by IgM ELISA using 33 paired serum samples of dengue patients admitted to the North Okkalapa General Hospital, Yangon, Union of Myanmar, in June and July, 1994. The antigen ELISA titer was found to be over 32 units in order to find out sufficient number of positive cases. This finding can be used as a reference for further experiments and the development of tetravalent dengue antigen for routine serodiagnosis of dengue virus infection

Opportunities and obstacles to the elimination of malaria from Peninsular Malaysia: knowledge, attitudes and practices on malaria among aboriginal and rural communities

<p>Abstract</p> <p>Background</p> <p>Despite continuous efforts by the government and private sectors, malaria is still a public health problem in rural Peninsular Malaysia. This study investigated household knowledge, attitude and practices (KAP) regarding malaria in two malaria endemic communities, forest-aboriginal and rural communities, in the Lipis district of Pahang state, Malaysia.</p> <p>Methods</p> <p>A descriptive cross-sectional study with a semi-structured questionnaire was carried out among 100 and 123 households from forest-aboriginal and rural areas, respectively.</p> <p>Results</p> <p>Knowledge about malaria and its transmission is significantly higher among the rural participants than the aborigines (86.2% vs 76%, p < 0.01). However, use of medicinal plants and beliefs in witchcraft and sorcery in treating febrile diseases were significantly higher among the aboriginal population (p < 0.01). There were no significant differences between the two communities in terms of the knowledge about malaria symptoms, attitudes towards its severity and practices in preventive measures against malaria by using mosquito bed nets. However, the knowledge and practice of different preventive measures to combat malaria, such as insecticide and the elimination of breeding areas, was significantly higher among the rural population than the aborigines (p < 0.001).</p> <p>Conclusions</p> <p>Both communities were aware of malaria as a disease, but knowledge, attitudes and practices were inadequate. Providing efficient health education to people residing in malaria endemic areas would improve their understanding about malaria prevention in order to bring about the elimination of malaria from the country.</p

Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers.

INTRODUCTION: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. METHODS: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and disruption of transcription factor binding, and were functionally analyzed in vitro and in vivo in normal and breast cancer cell lines. SNPs tagging the expression haplotypes were correlated with the total expression of several genes in breast tissue measured by Taqman and microarray technologies. The effect of the expression haplotypes on breast cancer risk in BRCA2 mutation carriers was investigated in 2,754 carriers. RESULTS: We identified common haplotypes associated with differences in the levels of BRCA2 expression in human breast cells. We characterized three cis-regulatory SNPs located at the promoter and two intronic regulatory elements which affect the binding of the transcription factors C/EBPα, HMGA1, D-binding protein (DBP) and ZF5. We showed that the expression haplotypes also correlated with changes in the expression of other genes in normal breast. Furthermore, there was suggestive evidence that the minor allele of SNP rs4942440, which is associated with higher BRCA2 expression, is also associated with a reduced risk of breast cancer (per-allele hazard ratio (HR) = 0.85, 95% confidence interval (CI) = 0.72 to 1.00, P-trend = 0.048). CONCLUSIONS: Our work provides further insights into the role of cis-regulatory variation in the penetrance of disease-causing mutations. We identified small-effect genetic variants associated with allelic expression differences in BRCA2 which could possibly affect the risk in mutation carriers through altering expression levels of the wild-type allele.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are